Book - Vertebrate Embryology (1949) 5

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I have decided to take early retirement in September 2020. During the many years online I have received wonderful feedback from many readers, researchers and students interested in human embryology. I especially thank my research collaborators and contributors to the site. The good news is Embryology will remain online and I will continue my association with UNSW Australia. I look forward to updating and including the many exciting new discoveries in Embryology!

McEwen RS. Vertebrate Embryology. (1949) IBH Publishing Co., New Delhi. 1949 McEwen: 1 Germ Cells and Amphioxus | 2 Frog | 3 Teleosts and Gymnophiona | 4 Chick | 5 Mammal | 1949 Vertebrate Embryology

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Contents

Part V The Early Development of the Mammal and its Embryonic Appendages

Introduction

IN taking up the development of the Mammal in a book of this type, intended primarily for college undergraduates, the writer faces a dilemma in the choice of material. For those interested chiefly in Zoology the comparative aspects of early stages in several selected Mammals, suggesting as they do evolutionary trends, are highly significant. On the other hand for those mainly intent upon the study of medicine the emphasis of interest is likely to be different. Such students, and many of their teachers, though willing to admit that the study of early comparative mammalian development is of some value, feel that for practical purposes they must begin to concentrate. Hence they prefer to consider chiefly the embryology, both early and later, of a single form. Preferably this would be Man, but since that is usually not practical, the next best thing is to select for study some readily available Mammal whose history is nearly akin to that of Man. That Mammal is generally the Pig. If space allowed, there is of course no reason why both these lines could not be followed in considerable detail. Unfortunately, however, in a book already dealing at some length with the Frog and Chick, space does not permit an extensive treatment of both topics. Consequently the following compromise way of treating the Mammals becomes necessary.


To begin with, it will be found desirable as in previous cases to go back of the start of the embryo itself, and consider somewhat the reproductive organs of the adults. This will be especially necessary in the mammalian females because of the special relation of certain of their organs to the reproductive process and to the developing young.


We shall then proceed with the comparisons of the early embryos of selected orders of Mammals with special emphasis upon the development and character of their extra-embryonic membranes and structures. This special emphasis is pertinent because we shall find that these membranes and organs are fundamentally similar to those already familiar in the Chick, and found in all Sauropsids, i.e., Birds and Reptiles. They are of present interest because of the manner in which both their origin and structure has been modified in the different mammalian groups to serve essentially their old functions. The modifications have resulted from the different environment in which the embryo and fetus of the Mammal occurs, and from the very special relations with the mother which this environment makes necessary. That there should be similarities in these structures as between the Mammals and the Sauropsids is of course natural in view of the known derivation of the Mammals from the Reptiles. The modifications in the mammalian orders selected then help to suggest the lines along which evolution has perhaps moved within that class.


Having thus compared the early stages of certain representative mammalian fonns, we shall finally concentrate upon one of them, i.e., the development of the Pig. The Pig, however, is an Ungulate, and the Ungulates are one of the groups whose earliest stages and extra-embryonic membranes have been chosen for comparative study. In this latter study, moreover, the Pig will be especially emphasized as an example of the group. Hence when we come to the detailed consideration of this animal it will not be necessary to start quite at the beginning. We shall simply pick up where the comparative account left olf.


Lastly, another device by which we shall endeavor to save space and time is the following: In the embryology of the Frog and Chick we have already twice gone over in some detail the development of all the main vertebrate systems. In the Chick, moreover, the processes in many cases are, as has already been suggested, very similar indeed to those found in the Mammal. Hence in the Pig we shall not repeat again in detail the development of each system. Instead we shall outline such development rather briefly, emphasizing only those points in which the process or structure in this animal significantly difiers from that in the Chick. Such treatment will of course be accompanied by as many illustrations as possible. This should be sufiicient, and will be so if the student of the Pig has reasonably well in mind the corresponding situations in the Chick. Anyone who does not have the Chick development clearly in mind will find it necessary to refresh the memory by reference back to the appropriate account in that form.

The Reproductive Organs of the Adult

The Male

The Testes and Their Ducts. — In the adult male Mammal there are normally two testes. These organs may be retained permanently within the body of the animal, as in the case of the Elephant; more commonly, however, they pass out of the body during development, and are contained either in two sacs, or in two chambers of a single one, the scrotal sac or scrotum. This is the case in the Pig. In some cases, however, as among Rodents, an intermediate condition occurs in which the testes descend into the scrotum only during intervals of sexual activity. Each testis consists of the usual seminiferous tubules, embedded in connective tissue and leading by way of vasa eilerentia to the respective vas deferens.

Accessory Organs.— ln the Mammal there are, in addition to the testes and other parts just noted, certain accessory organs connected with the more distal parts of the genital tract. These are the prostate glands, Cowper’s glands, and, in some animals (e.g., in the Pig and in Man). the seminal vesicles. The function of the glands is to furnish a suitable medium for the existence of the sperm after it leaves the organs of the male. The vesicles presumably assist both in the secretion of additional fluids and in storing the combined" sexual products or semen previous to its ejaculation. Finally, there is in the male Mammal a penis. This has a single duct, the urethra, which serves to discharge urine, and also to introduce the semen into the genital tract of the female.

The Female

The Ovary.—In the female Mammal there is a single pair of ovaries, and, as in the other forms studied, these organs are contained within the body cavity and suspended from its wall by a mesovarium. The ovaries are whitish ovoid objects, varying in size in different animals, but always relatively small. Thus in the Human Being, for example, each ovary is about 3-4 cm. long, and from 2-3 cm. wide, and they are about the same in the Pig. Fundamentally, their internal structure is similar to that already described in the Bird.

The Genital Tract.

The 0viducts.—As in the Bird, the ovaries are not directly connected with the Miillerian ducts or oviducts. The latter, sometimes OOGENESIS" 439

known as the Fallopian tubes, are, however, provided as usual with a typical fimbriated funnel, or infur.-dibulum, which serves to embrace the ovary when an ovum is discharged. The walls of the oviducts are made up as follows: On the outside is the serous membrane, next to that a layer of more or less mingled longitudinal and circular muscles, then a sheet of vascular connective tissue covered by ciliated epithelium. the connective tissue with its epithelium being known as the mucous layer.

From each infundibulum the respective duct proceeds to join the one from the opposite side. Between the infundibulum and the point of junction, however, there is usually more or less bending, and in many cases the duct actually starts anteriorly before curving backward and medially to unite with its fellow.

The Uterus and Vagina. — At some point distal to the infundibula ei ther above or below the region of junction, or in some cases both above and below, the character of the tract or tracts changes. The muscular wall becomes thicker as does also the mucous layer which now contains lymph spaces and many glands. The part or‘ parts of the genital tract thus characterized are then known as the uterus or uteri, and the thick» ened mucous layer plus its epithelium are referred to together as the uterine endometrium. When these changes occur entirely proximal to the point of union of the tubes so that there are two distinct uteri (Rodents) the condition is-known as uterus duplex. On the other hand when they occur both above and below the region of union (Carnivores and Ungulates) the situation is described as uterus bicornis. Finally, when the uterine character exists only in the fused part of the tract the-condition is called uterus simplex. _ Beyond the uterus, or uteri, as the case may be, there is a single passage leading to the exterior, known as the vagina. At the external end of the latter there are certain rudiments homologous with the penis of the male.

The Development of the Ovum up to Segmentation, and the Sexual Cycle

Oogenesis

The Oogonia.—The embryonic ovary of the Mammal contains the usual primordial germ cells which, as in the lower Vertebrates, have probably migrated thither from the walls of the gut. At first these cells lie chiefly in the outer epithelium or cortex of the ovary. According to most accounts this cortical epithelium thickens and then produces out-growths which push into the deeper mesenchyme. These outgrowths are the ovigerous cords similar to those described in the Chick, hut in this instance often called the cords of Pfliiger.1 As in the Bird, they contain both the female germ cells, or oiigonia, and numerous epithelial cells as well. In the Mammal, however, the two types of cells are not easily distinguishable from one another, and it is quite possible that some germ cells may arise in situ. from indiilerent cells of Pfliiger. During this period multiplication of all the cells goes on rapidly.




Fig. 247. — Section through part of the ovary of a Dog. From Kellicott (Chordate Development). After Waldeyer.

a. “ Germinal epithelium.” b. Ovigerous cords. c. Small ovarian follicles. :1. Older ovarian follicle. e. Ovum surrounded and attached to wall of follicle by cells of discus proligerus (cumulus oiiphorus), including those of the future corona radiata. f. Second ovum in follicle with e. (Only rarely are two ova thus found in a single follicle.) g. Outer layer of follicular capsule. h. Inner layer of follicular capsule. i. Membrana granulosa. k. Collapsed, degenerating follicle. L Blood-vessels. In. Sections through tubes of the parovarium. y. Involuted portion of superficial epithelium. z. Transition to peritoneal epithelium.


1 Also according to some recent studies by Gruenwald ('42) the development of the cords is somewhat more involved than this, and varies to some extent in different Mammals. The end result, however, is essentially as indicated.


At some time before the birth of the animal in which the ovary is contained the multiplication of the oiigonia is said to cease. As has been previously noted, however, this assertion is now seriously questioned, some workers (E. Allen, ’23, G. I. Hargitt, ’30, and others) maintaining that in certain cases at least the ova derived from the primordial germ cells all, or nearly all, disappear. These are then said to be replaced by new oiigonia arising from the peritoneal (germinal?) epithelium at intervals during the sexual life of the individual. In any event the cells are eventually arranged in nests or groups, each of which contains a single oogonium, the remaining epithelial cells in the group being destined to form the follicle.'The young ovum now enters upon the growth period as an oiicyte.


The Oocyte and the Graafian Follicle

At about this time, the, epithelial cells referred to begin to become arranged about the young ovum to form the highly characteristic mammalian or Graafian follicle. At first they constitute a thin flat layer only one cell thick, but soon multiply so as to form a mass of cells about the growing oiicyte. In one side of this mass there then appears a space, the follicular cavity, which gradually enlarges and extends around the sides of the oiicyte. These extensions, however, never quite meet. Thus the oiicyte, still closely surrounded by several layers of cells, is suspended within the follicular cavity, which becomes filled by a fluid, the liquor folliculi. Meantime, the outside of the entire follicle has become covered by a capsule (follicular capsule or theca) , formed externally of connective tissue (theca externa) and internally of cells, blood vessels, and nerves (theca interna).


The various layers and parts of the entire Graafian follicle may now be named, as follows: Beginning on the outside there is the follicular capsule (theca) with its inner and outer layer. Just within this, and bounding the follicular cavity, there are a few layers of the follicular cells forming the basement membrane, or membrana granulosa. Upon the side of the ovum where the cavity has not extended, a neck of cells reaches from this membrane to those cells which immediately surround the oiicyte. Thus the latter is attached to the inner wall of the follicle by this neck, which, together with the more peripheral of the cells immediately surrounding the ovum, is termed the discus proligerus or cumulus oophorus. Those of the immediately surrounding cells which have remained closest about the egg are now gradually elongated at right angles to the surface of the latter. Many of these cells remain attached to this surface for a time following ovulation when they become known as the corona radiata (Figs. 24-7, 248) . This brings us to the actual egg and its membrane.


Fig. 248.—F'ully grown Human oiicyte just removed from the ovary. Outside the oiicyte are the clear zona pellucida and the follicular epithelium (_ corona radiate) . The perivitelline space in this instance is not apparent. The central part of the oiicyte contains deutoplasmic bodies and the excentric nucleus (germinal vesicle). Superficially there is a well-marked exoplasm, or cortical layer. From Waldeyer (Hertwig‘s Handbuch, etc.).

The Mature Ovum And Ovulation

The Mature Ovurn. — The mature ovum in all placental Mam~ mals 2 is relatively minute, though naturally varying in size in different animals. Thus that of the Mouse measures about .075 mm. in diameter, that of the Dog about 0.14 mm., that of Man 0.135 mm., and that of the Whale 0.14 mm. (Hartman, ’29, ’30) . The reason for this minute size is the fact that mammalian eggs are virtually without yolk (alecithal). They consist of a central region of opaque endoplasm surrounded by a thin layer of exoplasm, and within the former is a relatively large nudens (germinal vesicle), somewhat excentrically placed.

  • It will suflice to state at this point that the term placental Mammal includes the vast majority of the group. Its exact significance will be fully described in the section on the yolk-sac, allantois and placenta (see below).


The ovum apparently does not possess any true vitelline membrane. It is surrounded, however, by a thick transparent substance which is presumably chorionic, i.e., is secreted by the cells of the follicle. This layer, though clear, frequently appears to be perforated by minute canals through which processes of the follicular cells reach the egg to nourish it. It is, therefore, known either as the zona pellucida or the zona radiata. There is usually a slight space between this zone and the iprotoplasm of the egg, and though there may be no vitelline membrane this space is known as the perivitelline space (Fig. 24-8) .

Ovulation

As a Graafian follicle and its ovum matures, it is gradually brought to the surface of the ovary. At the same time one side of the follicle becomes thin in connection with the formation of a cicatrix, as in the Chick. As complete maturity is reached, the discus proligerus is broken and the ovum floats freely in the liquor folliculi. In most animals rupture of the follicle then occurs spontaneously, and its contents is received by the infundibulum of the oviduct. In a few forms, e.g., the Rabbit and Cat, the breaking of the ripe follicle does not usually occur spontaneously, but only following copulation with the male (coitus). The liberation of an ovum may or may not take place in both ovaries at once, and there may or may not be more than one follicle ready for discharge in the same ovary at approximately the same time. These variations, moreover, may occur normally in the same species of animal. In Mammals which ordinarily produce a litter of young, however, the discharge of several ova at once is of course the usual thing.

The Sexual Cycle in the Female

lt is well known that like many other animals, Mammals are capable of breeding only during certain periods or seasons. Among this group, moreover, these periods are far more marked in the female than in the male. In the former sex they are also very definitely related to the process of ovulation so that it seems desirable to discuss the subject at this point. In all placental Mammals which have been carefully studied, it is known that during sexual life the walls of the uterus suffer a series of periodic changes, interrupted only by pregnancy. The placentals, moreover, may be divided into two main groups with respect to these uterine changes, i.e., the Primates and the non-Primates.

The Non—Primate Cycle. —Among this group the stages involved are fundamentally similar, and these stages are well represented in the Pig‘, whose embryology will later be considered. We shall begin therefore by a description of the sexual cycle in the female of this animal. In the sow each sexual or oestrus cycle, as it is called, occupies twentyone days and in the absence of pregnancy, the cycles are continuous throughout the year. As regards the behavior of the animal, the activity of the ovary, and the condition of the uterine endometrium, the periods or phases of a cycle are characterized as-follows:

I. The Dioestrum. — During this period lasting about two and one half weeks the sow occupies herself with eating and sleeping, and shows no interest in the opposite sex. A study of her ovaries, however, shows that within this interval an important event takes place. The empty follicles which remain from the immediately preceding ovulation become filled with a specialized type of fatty cell. In some cases (Man) these cells are yellow in color, which has caused each body so formed to be known as a corpus luteum. In the Pig, however, these bodies are pinkish. They quickly develop to a maximum extent, and persist in this condition for about the first thirteen to fourteen days of the period, at which time they begin to regress. Correlated with the time of development and persistence of the corpora lutea in the ovary, the uterine mucosa, which was already quite thick at the beginning of this period, becomes even more hypertrophied, especially the glands. This is a con-_ dition known as pseudopregnancy, because, as we shall see, the state of the mucosa at this time resembles to a considerable degree its character during true pregnancy, and due to the stimulus of the same hormone, progesterone (see below). Finally as the corpora lutea regress the uterine mucosa likewise regresses, and within two or three days has become relatively thin (F 249, A ). Thus during the last day or so of the dioestrum there is virtually nothing going on in the uterus so that this brief interval may be thought of as a time of more or less complete “ rest ” for that organ.

II. The Pro-oestrum.—Following the dioestrum there is a short interval of a day or,so generally known as the pro-oestrum, within which the behavior of the animal remains about as before. Studies of her ovaries, however, reveal that undeveloped Graafian follicles are starting a rapid growth, while the uterine mucosa also has again begun to hypertrophy (Fig. 249, A)

III. The Oestrus. — This period, lasting approximately three days, is known as the time of “ heat,” and during it the sow becomes extremely restless and will accept mating at any time. Examination of the ovaries shows that the Graafian follicles come to maturity at about the middle of this period, and at that point ovulation occurs. The corpora lutea, already referred to, immediately start development which, in the absence of pregnancy, continues into the succeeding dioestruxp as already described. The hypertrophy of the mucosa, well under way at the end of the pro-oestrum, also continues on through oestrus and into the succeeding dioestrum, during most of which periods it remains at a high level as indicated (Fig. 249, A) .



Fig. 249.—Diagrams comparing the events of the oestrus cycles of the Pig and Dog with those of the ovulatory and non-ovulatory menstrual cycle in Man. The line vertical rulings in the cycle of the Dog and in those of Man indicate the time of occurrence and the approximate relative degree of bleeding in each case. There is no normal obvious bleeding in the Pig. The rise and fall of the curved lines indicates the relative degree of hypertrophy or degeneration of the tissues or bodies designated.


Variations in the Non-Primate Cycle.—-The non-Primate cycle as thus described for the Pig may be considered typical for the nonPrimate group of animals so far as its fundamental aspects are concerned. As already suggested, however, there are numerous variations in detail, some of the more striking of which will now be noted. Probably the most outstanding is that which occurs in animals like the Dog and Cat. In these animals there are only two or three oestrus periods a year, with a long inactive interval, known as an anoestrum between each period of “ heat.” In such cases the corpora lutea, and the uterine hypertrophy in the absence of pregnancy, only persist for a relatively short time, the uterine mucosa being comparatively thin during most of the long anoestrum. Breeding of course can only occur during the oestrus periods which are hence referred to as the breeding seasons. The Dog and Cow are further peculiar in that at the end of the pro-oestrum the blood vessels of the hypertrophied mucosa are so gorged that some superficial bleeding occurs. This quirk‘ led to much discussion and misapprehension of the relations between the non-Primate and Primate cycles as we shall presently see. Another peculiarity of a few animals such as the Cat and also the Rabbit, as already noted, is the fact that ovulation in these forms is not spontaneous during oestrus, even though the mature ova are present. It only occurs at this time if copulation, or some form of stimulation which simulates copulation, takes place. Otherwise the ripe follicles simply degenerate, no corpora lutea are formed, and hence no pseudopregnancy occurs (see below).


Not only do animals vary as between those with a succession of relatively short dioestrus cycles like the Pig, and those with long anoestrus intervals like the Dog (Fig. 249, B), but in the latter type some forms have several short dioestrus cycles between each anoestrum. That is they have a breeding season perhaps once a year like some sheep, and during that season they come into “ heat ” several times. Animals with only one oestrus period at a breeding season are said to be monoestrus, while those with several at each season, or with continuous short cycles, are polyoeszrus. Lastly the length of the dioestrus cycles varies greatly among different anmials. Thus, while it is twenty-one days in the Pig, it is only five days in the Rat and Mouse, and fifteen in the Guinea-Pig. It should be emphasized also that these are average times. There is commonly some variation in cycle length even in the same individual, depending upon temperature, food and other unknown conditions.

The Primate Cycle.—In discussing this group it should at once he pointed out that the peculiarities about to be described do not actually apply to all Primates, e.g., to Lemurs and to the New World Monkeys. They do, however, apply to the Anthropoid Apes, the Old World Monkeys and to Man. ‘The most complete studies have been made on Man and Rhesus, an Old World Monkey, and we shall therefore consider the situation particularly as it applies to these forms, and first especially as it applies to Man.

The Menstrual Cycle. — The peculiar characteristic of the sex cycle as it occurs in the Human female is the inclusion within it of the phenomenon of menstruation, from which the whole cycle takes its name. The nature of this phenomenon, and its relation to the parts of the nonPrimate cycle, in so far as it can at present be related to them, is as follows:

Keeping the Pig in mind as presenting a typical example of the situation in the non-Primates, we find that the first but least important difierence between that animal and Man is in the length of the entire cycle. Thus in the Pig, as just noted, it is about twenty-one days, while in both Women and the Rhesus monkey it is normally twenty-eight days,

with numerous more or less minor variations. Proceeding next to a com parison of the periods within the cycle, and starting with the one in Man

presumably homologous with the dioestrum in the lower animals, we

find conditions at that stage in the Human subject about the same as in the sow. That is to say there is no sexual urge at this time, the ovary contains a corpus luteum, and at the beginning the uterine mucosa is hypertrophied. This phase, comparable with the first and major (pseudopregnant) part of the dioestrum, lasts for about two weeks. At the end of this time, as in the lower forms, the corpus luteum disappears, and accompanying this the uterine epithelium regresses. In this instance, however, this regression instead of being relatively quiet and uneventful, is a rather violent affair involving a serious breakdown of the endometrium, both mucosa and epithelium. This is accompanied by a sloughing of? of cells and considerable bleeding, and it is this process which comprises menstruation. Following this as in the Pig, comes a “ rest ” interval, in this instance, however, lasting four to five days and involving repair of the preceding damage, though the mucosa remains relatively thin. Menstruation plus this interval would therefore correspond to the end of the dioestrum in the Pig, except that in that animal the process of regression is much less violent. Hence the menstrual features are lacking, and no “ repair ” is required during the “ rest ” interval. The next period should be that of the pro-oestrum, and apparently something essentially similar to this in the lower animals exists in Man. As in the former case it apparently involves no accentuation of sex interest, the ovary contains a maturing Graafian follicle, and the uterine mucosa begins again to hyper-trophy. This lasts five to six days. Following the “pro-oestrum” the next period should be that of oestrus, but this is another respect in which the Primate cycle difiers from that of the non-Primates. There is no oestrus. This means that there is no time in the cycle of greatly heightened sexual activity. Ovulation, which "should occur sometime during oestrus, occurs at the end of what we are calling the “ pro-oestrum,” though the use of this and other "terms relating to the oestrus cycle is obviously questionable in a cycle in which there is no oestrus. This is why the Primate cycle is commonly referred to as the menstrual cycle in correlation with its most outstanding characteristic. Following ovulation a corpus luteum of course exists, and in the absence of pregnancy a new “ dioestrum ” begins, culminating in another menstruation and “ rest” interval (Fig. 249, C). From this account it will be evident that ovulation occurs about midway between menstruations, i.e., from the twelfth to the sixteenth day following the beginning of the last menstrual period (Corner, "43) From this it is clear that menstrual bleeding has nothing whatever to do, either in relative time of occurrence, or in character, with the minor ‘bleeding of the pro-oestrum in an animal like the Dog, a phenomenon with which it was once confused. In this connection it should he noted that a slight pro-oestral bleeding also. occurs in the Rhesus Monkey and occasionally in Women, in which cases -it is known as intermenstrual bleeding or Hartman’s sign, i.e., a sign of imminent ovulation. To summarize a comparison of the two cycles, then, we may say this: In both there is what amounts to a “ dioestrum” during which sexual activity is not evident. The ovary contains a corpus luteum during the first part of this period, and during this part the uterine mucosa is hypertrophied. Near the end in both cases the mucosa regresses, but in the Primate cycle the regression is much more thoroughgoing, and is termed menstruation,_ Finally a short quiescent interval ensues which in E the Primates is occupied with uterinerepair. In both cycles a “proM 5 oestrum ” follows the “ dioestrum ” involving no change in sex activity, but the growth of a new Graafian follicle and renewed uterine hyperI trophy. In the norn-Primate cycle this is followed by oestrus or “ heat ”


  • in the midst of which ovulation occurs. In the Primate cycle ovulation occurs at the end of what we have called, for the sake of comparison, the “ pro-oestrum,” and there is no oestrus. Instead the “ dioestrum” immediately follows, and the cycle is complete.

Having thus described the oestrus and the menstrual cycles there remain the problems of their causes and functions. Much work has been done in this connection over a long period, but it is only within recent years that the pieces of the puzzle have begun to fall into some semblance of order. As will presently appear, however, there are even yet some pieces which are missing.

Causes qf the Oestrus and Menstrual Cyc1es.——It is already evident that certain events in both the oestrus and menstrual cycles are closely correlated. Thus we have seen that when a follicle is developing in the ovary the uterine mucosa in either cycle is undergoing its prooestral hypertrophy. As the corpora lutea form it undergoes still further hypertrophy, and when these latter bodies start to disappear this mucosa regresses, either with or without extensive breakdown. Why is this? The answer is found in the fact that the developing follicle produces a hormone called oestrone (theelin) which causes the initial pro~oestral hypertrophy. It also of course causes the behavioral phenomenon of “ heat” in most “ lower ” animals?‘ As the corpora lutea form following ovulation they also produce orie or more hormones, including some oestrone. The most prominent of these, however, is called progesterone, and this causes the still further uterine hypertrophy of the first part of the dioestrum. Both these hormones are sterols, have been obtained in pure crystalline form, and their action repeatedly demonstrated experimentally. The withdrawal of the progesterone as the corpora lutea begin to disappear would then explain both the dioestral regression and the menstrual breakdown of the mucosa previously built up. The follicular and luteal hormones produced in the proper order and then withdrawn would therefore seem to account satisfactorily and completely for both types of cycle. This would be true were it not for one curious fact. It was discovered (Corner, ’23) that Rhesus monkeys, and probably more rarely Women, experience menstruation without ovulation, and hence in the absence of corpora lutea. The monkeys, it should be noted, have a breeding season (the winter months), and it is at the beginning and end of this season that these so-called anovulatory cycles occur. Women of course have no such season, and in them cycles of this character have been thought to occur most commonly in girls beginning to menstruate. It is now known, however, that such anovulatory cycles, Otllu ». xse apparently normal, occur in a certain percentage of women during their active sexual life. Indeed it has been proven that such women may only actually ovulate two or three times a year in spite of seemingly normal menstrual periods, causing serious interference with lertility. In any event such cycles obviously upset theforegoing neat explanation of the entire phenomenon. Much work has been done in an effort to solve this problem, but no completely satisfactory answer has yet been arrived at. It is known for instance that in castrate animals an apparently normal cycle can be produced by the injection and sudden withdrawal, after a suitable interval, of oestrone alone. Yet in non-castrate animals extra doses of oestrone will not prevent the uterine breakdown. A little progestrone, however, will do so. Hence the latter substance seems clearly to have some important part in the cycles of normal ovulating animals, probably in the manner already described.

3 Just what parts of the follicle are responsible for this hormone is not alto» gather certain, but probably either the theca interns. or the granulosa or both.




With these facts in mind two possible explanations of the anovulatory cycle may be briefly noted. One, considered by many the most probable, is that a certain amount of oestrone is necessary, first to build up, and then to maintain, the uterine endometrium in a state of preovulatory hypertrophy. This hypertrophy is of course not quite like that produced by progesterone, but is nevertheless considerable. The necessary oestrone for this is furnished by the partially developed follicle, which instead of going on to ovulate, persists for a time, periodically regresses, and is replaced by another. The regression of course produces a temporary lack of oestrone, and an anovulatory endometrial breakdown very similar to menstruation occurs (Fig. 249, D). The second possibility, suggested by Hisaw, is that the partially developed Graafian follicle produces not only oestrone, but a little progesterone as well. Then if, in the anovulatory cycle, the production of the progesterone for some reason, such as the-regression of the follicle, declines, this may be enough to produce menstruation even in the absence of ovulation and the ensuing corpus luteum. There is a little suggestive evidence for this, but it is diflicult to prove. So much for this part of the oestral cycle and menstrual mechanism.

4 It may be added that these hormones also have several other significant’ effects not directly pertinent to the present discussion. Thus oestrone not only starts the hypertrophy of the mucosa in each cycle, but is necessary to bring the infantile uterus to a stage of development where progesterone can act on it. Also it controls the growth of the muscles of the pregnant uterus, first stimulating, and then checking, and causes corfiification of the vagina of the Guinea Pig, thus revealing its presence in this animal. Lastly it stimulates development of the breasts to a condition where they can be acted on by the pituitary hormone, prolactin, but at the same time prevents milk flow until birth. Progesterone in addition to its elfect on the uterine mucosa has a decidedly quieting action on the normal rhythmic contractions of the uterine muscles, and is said by some to cause relaxation of the pelvic,

There still remains the question as to what sets ofl" these cycles, i.e., what starts the follicles to developing, and what stops them. The answer to this appears to be found in that gland-of-all-work, the pituitary. The anterior lobe of this gland is known to produce, among other things, a follicle stimulating hormone (F.S.H.) which causes Craafian follicles to begin their growth. What then seems to happen is that when the growing follicle achieves a certain output of oestrone this acts in turn to suppress secretion by the pituitary. (There is some experimental evidence for this.) The follicle then ovulates, and its extensive oestrone production ceases, thus allowing the pituitary secretion to rise again, and so the cycle repeats itself. Here again, however, a problem arises which has not been entirely satisfactorily answered. The scheme just presented works well enough for animals like the Pig or Man with continuous cycles, but what of those with an anoestrum? What causes the cycles to stop? We do not know. It has been suggested that during the anoestrum in such animals as the Dog or Cat the secretion of the pituitary and the ovarian follicle, exactly balance each other so that nothing happens. Perhaps so, but < there is no proof of it. Also if this is true, what produces an unbalance. and starts off a new cycle?

Functions of the Female Cycle. —- Thus far the oestrus and menstrual cycles have been considered without reference to the possible occurrence of pregnancy. As might be suspected, however, each cycle is in fact an invitation to, and a preparation for, this important event. In cases where oestrus occurs the behavior of the female is such as to permit and encourage mating at this time, and it is of course at just this

point also that a ripe egg is released into the oviduct ready to be fertilized. In the menstrual cycle the same thing is true, except that here I there appears to be no special sexual urge at the time of ovulation. Fol’ lowing this event in either case the egg is subject to fertilization in the upper end of the oviduct. If this occurs the egg becomes what amounts to a blastula in a manner to be described below, and after 3-4 days finds its way into the uterus. Here meanwhile the climax in the hypertrophy of the uterine mucosa is coming about. It now appears that this hypertrophy is just what is needed to insure the firm attachment of the developing egg to the uterine wall by a process known as implantation. This


ligaments of the Guinea Pig. Hisaw, however, has claimed a separate luteal hor) mane, relaxm, to be responsible for this. In some cases progesterone also acts as an.

acciassory in aiding the oestrogens to prepare the breasts for final stimulation by pro actin. -n.7<ma.t:..a


process varies considerably in different animals, and will be discussed at some length later on. The point to be noted at the moment is that apparently the hypertrophy of the mucosa is a necessary preparation for it. As has been noted, if fertilization and implantation fail to occur, the hypertrophy regresses and a new cycle is initiated, with, as M.- 3. Gilbert so cleverly suggests in her book, Biography of the Unborn, “ hope for better luck next time.” On the other hand, if implantation does occur, the hypertrophy persists and in fact increases. Because of the similarity of this hypertrophy to that of the dioestrum, the latter, as previously noted, is frequently termed pseudopregnancy. This persistence of the hypertrophy when it is needed, and its disappearance when it is not needed leads to some further questions to which we have at present only partial answers. Some of these questions and the tentative answers are as follows: .

What for instance makes the hypertrophy of the mucosa persist in pregnancy and not at other times? In this connection it is of interest to find that in many animals the corpora lutea also persist throughout pregnancy instead of disappearing as in the non pregnant cycle. Is there a causal connection here? It would appear that in those cases where both corpora lutea and mucosal hypertrophy persist together there is. Thus in the Rat and the Cow removal of the corpora lutea of pregnancy causes regression of the mucosa and abortion, though in other cases, like that of Man, this is not true. The answer as to what makes the hypertrophied uterine mucosa continue in the former animals then seems to be fairly clear. It will be recalled that one of the chief hormones of the corpus luteum is progesterone. This hormone, however, was so named because of the very fact that it maintains an ‘hypertrophied condition of the mucosa not only during most of the dioestrum, but especially during pregnancy. Thus the corpora lutea apparently rather obviously persist during pregnancy in these cases in order to secrete the progesterone which maintains this condition. There is also, as noted, evidence that the corpora lutea produce some oestrone, or something closely akin to it. This and the progesterone appear to assist in causing the hypertrophy of the muscles of the uterus as well as that of the mu~ cosa during pregnancy.

The next question is, how do the corpora lutea know, so to speak, when to persist and when not to? The answer to this appears to be that the organ which attaches the embryo to the uterine wall, termed the placenta, itself secretes several hormones, one of which is luteinizing, i.e., helps to keep the corpus luteum developed. There is also a pituitary hormone which has a luteinizing efi'ect, but this is apparently not the one chiefly involved during pregnancy. _As just suggested the placenta pro " duces other hormones, i.e., oestrogens (oestrone like hormones), and also quite definitely progesterone. This source of these substances, it is now generally agreed, soon becomes the main one in cases like Man where the corpus luteum functions for only about the first four months of pregnancy, being operatively removable after the first few weeks without harm.

Also, in Man at least, certain other gonad stimulating hormones, similar in action to the F.S.H. of the pituitary, are produced by the placenta. They are called Prolan A and B, and are used in the Aschheim-Zondek or Friedman tests for pregnancy. Thus so much of these hormones is produced under this condition, even within the first month, that they are excreted in the urine. Advantage is taken of this fact to make a test for their presence, and hence for pregnancy, by injecting a specified amount of the suspected urine into a female rabbit (Friedman test). If the hormones are present they will cause the animal to ovulate within ten hours.5 The particular tissue of the placenta from which these various sterol substances appear to be derived in Man and Monkeys is a special material called trophoblast to be described below (Wislocki and Bennett, ’43; Baker, Hook and Severinghaus, ’4-4) .

Finally, in this connection, what if any function has menstruation as such? It would indeed be comforting to be able to assign it one, but to date no adequate explanation for this excessive breakdown of the uterine endometrium exists. It seems to be merely an overenthusiastic expression in some Primates of the regression following luteal hypertrophy and withdrawal which occurs in a more restrained manner in other more humble Mammals.

Parturition. —This is a process which might naturally be considered at the conclusion of development rather than here. However, possible dependence upon the hormonal substances which we have been discussing makes this an appropriate point to mention the factors which may be involved. As a matter of fact there is not a great deal to say, because comparatively little is really known as to just what factors are actually concerned in this phenomenon. It may be that among others a

- reduction of progesterone, which quiets uterine contraction, and an in crease in oestrogens, which are known to stimulate it: play a part. This,

5 Another peculiar effect of these hormones is to cause the release ‘at sperm from the testes of the Frog when so-called pregnancy urine is injected into a lymph sac of one of these animals. This fact furnishes another pregnancy test which promises to be of value ( Miller and Wiltberger, ’48). 504 EARLY MAMMALIAN DEVELOPMENT

however, is only a guess, and according to Corner many other elements such as the balance of still other hormones, the rate of blood flow through the placenta, the state of nutrition in the fetus, and probably various other conditions are concerned. Indeed some have claimed that the mere size and weight of its tenant finally irritates the uterus into initiating the contractions of labor. Some evidence for this latter notion is perhaps furnished by certain cases in the Cat studied by Markee and Hinsey (’35) . In an abnormal situation in this animal one horn of the uterus contained embryos differing considerably in age from those in the other, a condition known as superfetation. In this case the born with the older fetuses delivered itself thirteen days ahead of the other, the normal full term in this animal being from sixty-three to sixty-five days. This would thus seem to indicate that the conditions responsible for delivery are not entirely hormonal, and hence general, but are at least partly quite local. These investigators also showed that thickness of endometrium and muscle depends on the number and weight of fetuses present in the horn in question. This again emphasizes the effect of local factors on conditions which may "affect delivery. In concluding this topic it is pertinent to note the normal term of gestation in the animal we are about to consider in some detail, i.e., the Pig. As usual this period varies slightly with breed and other factors, the range being from 112-115 days, or just under four months (Asdell, ’46) .

The Sexual Cycle in the Male

As regards the male among Mammals, it is found that here also there is a tendency toward cycles of sexual activity. This phenomenon, however, is not so common as among the females, or among the males of lower forms. In thosespecies of Mammals in which the male does experience special periods of heightened sexual desire, however, these normally coincide with the breeding season of the female, and are known as the rutting periods. At such times the males may develop very special secondary sexual characters, such as the antlers of the buck deer, as well as great irritability and desire for combat with other males. On the other hand, the males of many Mammals have no such special periods of sex activity. Instead, they are apparently able to breed at any time, even though the females of their kind will only receive them at certain seasons.

With this understanding concerning the nature of the sexual cycle and its relation to ovulation and sexual activity, we are now prepared to return to the history of the ovum.’

Maturation And Fertilization

Although in Mammals the first maturation division often occurs before ovulation and fertilization, the second, with apparently only a few exceptions (e.g., the Mole, Rabbit, and probably Man) occurs after Fig. 250.——Reconstruction of four sections through the fertilized ovum of the Cat. From Longley (combined from two figures). No zona pellucida is visible in these sections. The corona radiata is disintegrating.

s. Remains of second polar spindle. I. First polar body. II. Second polar hody. o”. Sperm nucleus. 9 . Egg nucleus.

ward. Hence it has seemed best to mention both divisions in connection with the latter phenomenon.

The First Maturation Division.—At some time during the growth of the oocyte, the preliminary stages of maturation are completed without any peculiarity of note. The first polar, spindle is then formed, and usually a short time before ovulation the first polar body is given off. In the latter connection the only feature to be noted as pe ‘culiar to Mammalsis the fact that this polar body is normally relatively

large, i_.e., often as much as one fourth the diameter of the ovum itself, 506 EARLY MAMMALIAN DEVELOPMENT

and in abnormal cases sometimes equal to .the latter. The fate of these exceptionally large bodies is not known. After the extrusion of the first polar body, the spindle for the second is formed and moves into position for division. The completion of the process may then take place in the ovary (e.g., in the Mole and Rabbit) or it may be inhibited while ovulation and fertilization occur.

Fertilization. —— Sperm introduced into the vagina of the Mammal rapidly make their way into the uterus and up the oviducts. A few hours

0

Fig. 251. — Cleavage of the ovum of the Rabbit. From Kellioott (Chordate Development). After Assheton. A. Two-cell stage, 24- hours after coitus, showing the two polar bodies separated. B. Four-cell stage, 25% hours after coitus. C. Eight-cell

stage. a. Albumenous layer derived from the wall of the oviduct. z. Zona radiata.

or even less suiiices for them to reach the upper ends of these ducts where the actual process of fertilization usually takes place. Considerable work has been done on the rate and method of progress of the sperm up the oviducts of different animals. Thus Parker (’31) showed that in the Rabbit the sperm are transported up, both by contractions of the tube and by cilia, despite the fact that the latter beat in an abovaxian direction. By contractions the tube is divided into small compartments, and as soon as sperm get into the first of these they are spread throughout it by ciliary currents which move down the walls and up the middle of the compartment. Then the location of the contractions shifts, and new compartments are formed. Sperm do of course swim, but as just suggested, this auto-motility is not the only, or even the main factor, involved in getting them to the upper end of the oviduct. In the Sheep, Schott (’4l) found the sperm to reach the upper ends of the ducts in about twenty minutes, and to travel at the rate of 4- cm. (40 mm.) per minute. He does not, however, state that they swim at that rate. Phillips and Andrews (’37) claim an average swimming speed in vitro of only 4.83 mm. per minute over a distance equal to the length of the ewe genital tract, though they do much better at first. In the ewe, however, they travel, according to these authors, by swimming or otherwise, at a rate of at least 12.4 mm. per minute. In the Rat, Blandau and Money (’44.} say that in twenty-six out of thirty cases sperm reached the infundibulum in forty-five minutes. They do not say just how, but Rossman (’37) suggests a peristaltic activity of the uterus as responsible for mnvement through that region. In this connection Asdell (’46) also notes that contractions of the uterus probably aid in the transport of the sperm, but gives the “ average” time required to reach the infundibulum “in all animals studied ” as about four hours. This, it will be noted, is considerably longer than any of the times indicated above, and he does not say what animals were involved. This author further states that none of the first few sperm to reach an egg fertilize it, but they do secrete an enzyme, hyaluronidase, which disperses the cells of the corona radiata, thus making the egg accessible to one of the sperm which follow. He states that about one million sperm at an insemination are necessary to insure fertilization by the one sperm required per egg This is obviously only a rough estimate, since the kinds of animals, and the numbers of eggs are not given.

Most recently some interesting data have been acquired concerning these matters in relation to Man. These data were presented at the Washington meeting of the American Society of Zoologists (’-48) by Dr. E. J. Farris under the title, “ Motile Spermatozoa as an Index of Fertility in Man,” and the results are ‘quoted with the author’s permission. According to this investigator Human sperm swim in vitro at the rate of 3 mm. per minute, a rate not so different for one of those claimed for the Sheep. This author admits, however, that other factors, such as those indicated above, are also active in the movement of the sperm in the fe«’ male genital tract, and claims that actually they reach the ovum at the upper end in about an hour. This is much better than the “ average time in all animals studied ” given by Asdell. Farris also notes that at least 130 million motile sperm per c.c. of semen, and preferably more, are necessary to insure fertilization. ‘

Aside from such studies there are others indicating the time which sperm retain their fertilizing capacity. In the Rat, Soderwall and Blandau (’41) say it is at the most fourteen hours, and that it falls off considerably after ten hours. In the Guinea Pig, on the other hand, Soderwall and Young (’4«O) place the maximum time at twenty-two hours, while in Man, Farris places it at twelve hours, even though the sperm may remain motile much longer than this. An extreme survivaltime is found in the Bat where insemination occurs in the fall, and the sperm apparently survive and retain fertilizing capacity in the hibernating females all winter (Wimsatt, ’44) . ' The functional survival of the egg previous to fertilization has also been studied, ‘though not so extensively as in the case of the sperm. It is said, however, to be able to retain its fertilizability for ten hours in the Rat (Blandau and Jordan, ’41), and for twenty hours in the Guinea Pig (Blandau and Young, ’39) .



Fig. 252.—Semi-diagrammatic sections through stages of early cleavage, blastula tblastocystt and early gastrula of the Pig. After Heuser and Streeter. A. Early cleavage. B, C and D formation of biastocyst with inner cell mass. E. S:art of epihlast and hypohlast differentiation (gastrnlation), probably by delamination. or possibly some infiltration. of cells from the inner cell mass. Trophoblast, often first called subzonal layer.


From these data it will be evident that even though ovulation may not occur so that an egg is present at the moment sperm reach the upper end of the oviduct there is still good opportunity for fertilization to occur there over a reasonable period. When a viable sperm does reach an egg it malies its way through any remaining cells of the corona radiata and through the zona pellucida which still cover it. Usually only one actually enters the egg, presumably due to mechanisms similar to those previously described. In many cases, only the head and middle piece of the sperm enter, but in others (Mouse), the entire spermatozoon is taken in; when this does occur, however, the tail soon degenerates. The head of the sperm next forms the sperm nucleus (male pronucleus) in the usual manner.

The Second Maturation Division. — If this has not already been completed its completion occurs following the entrance of the sperm and while the nucleus of the latter is forming; it results in a second polar body, usually smaller than the first. This division is soon followed by the union of the sperm and egg nuclei, and the process of fertilization is complete (Fig. 250).

Segmentation, Gastrulation, Amnion Formation, And The Primitive Streak

Segmentation

The Type of Cleavage. — Segmentation in the placental Mammals is total, as might be expected from the virtual absence of yolk. The arrangement and behavior of the cells, however, is quite different from that observed in the first yolkless form which was studied, i.e., Amphioxus. The reason for this is apparently due to the fact that the egg of a Mammal is almost certainly only secondarily without yolk. The evidence for this assumption will become more and more obvious in the course of this chapter, but a couple of the more striking proofs may be indicated here. Thus as will appear, the embryos of the primitive non-placental Mammals known as Monotremes possess both yolk-sac and yolk, while all the placental Mammals retain the sac, though it is empty. Secondly, there are the origin of the embryo from what amounts to a blastoderm. the method of gastrulation, and other features all characteristics of large-yolked forms. We may now proceed to the actual method of segmentation. _

The Blastocyst.——Cleavage, though total, is irregular from the start (Fig. 251) . The result is the formation of a spherical mass of cells known as the morula in which the cells are of two types. On the outside they are at first cubical, but soon assume the form of a flattened epithelium, which being covered temporarily by the zona radiata is called

the subzonal layer, later the trophoblast. The cells on the inside, on the other hand, are spherical and are called the inner cell mass. Presently,

vacuoles appear on one side of this mass, beneath it and the subzonal layer. These run together and increase until more than half of the morula is occupied by a fluid-filled cavity. On the other side, the inner mass hangs from the wall like a suspended drop (Fig. 252). The morula has now become a ‘blastodermic vesicle or bldstocyst, which corresponds in a general way to the blastula of lower forms. Hence the cavity may be termed the blastocoel or subgerminal cavity, while the fluid within it occupies the place of the yolk. Finally, as subsequent development shows, the inner cell mass lying above the fluid virtually plays the part of a blastoderm (Fig. 253).

Cleavage occurs while the ovum is passing down the oviduct, and in some instances it may even have reached the blastocyst condition by "the time it arrives in the uterus. The time required for this passage varies ‘ much in different animals, but is ordinarily considerable, e.g., about four days in the Rabbit, and eight or ten days in the Dog. The movement down the duct is apparently accomplished mainly by peristaltic action, though in the Rabbit, Parker claims that the cilia heating in-an abovarian direction are involved.

Within the uterus the cleaving egg, or morula, soon becomes a blastocyst, if it is not already one, and this begins to enlarge through


Fig. 253.—-Section through the fully

formed blastodermic vesicle of the Rabbit,’ From Quain’s Anatomy, after Van Beneden.

f.c.m. Granular cells of the inner cell mass. troph. Trophoblast. zp. Zona pellucida.

the multiplication and flattening of the cells of the subzonal layer

(Fig. 253). There is considerable variation in the size and shape

_ which is reached in this manner. Thus in the Rabbit, the vesicle after three days in the uterus becomes ovoidal, measuring about 4.5 x 3.5 mm. In Ungulates, on the other hand, it becomes very long and tapering, that of a nine day Pig measuring about 8am. in length and .5 mm. in diameter, while in a day or two more the length has reached about a meter, and the diameter a few millimeters. In all cases, however, the inner cell mass remains very small, and in instances where the vesicle is elongated, as in the Pig or Sheep, the mass is attached about midway between its ends (Fig. 254) .

Gastrulation

As in the other forms studied, this term is here used to denote the formation of an archenteric cavity, and the setting aside of epiblast and kypoblast. In most Mammals the latter appears to arise either by a splitting off (delamination) of cells from the ventral side of the inner cell mass, or by an infiltration of cells from this area. It will be recalled that both these possibilities are identical with some of those recently suggested as occurring in the origin of the primordial hypoblast of the Chick. At all events the cells so ‘produced then multiply and spread around the inside of the vesicle until in many forms they eventually completely line» it, just ‘as they line the archenteron ‘and yolk-sac of the Bird. This extension of the hypoblast and later mesoderm around the inside of the blastocyst is of course essentially epibolic, though the overgrowth covers only a cavity. The cavity so lined constitutes the archenteron, while part of it presently becomes the yolk-sac in a man


Fig. 254.——Photographs of Pig blastocyst by Heuser and Streeter showing the transition from an oval to an elongated form. In group A the long axis of the smallest specimen was approximately 7.5 mm., while in the largest it was about 13.8 mm. In group B the magnification is less so that the smallest specimen on the extreme left actually measured about 15 mm. in length, and the greatly elongated specimen at the top of the group measured about 150 mm.


Fig. 255.—Sections through four stages in the early development of the lnsectivore Tupaia jauanica. From Hubrecht. A. Blastodermic vesicle completely closed; hypoblast still continuous with the embryonic epiblast. B, C. Embryonic epiblast split and folding out upon the surface of the vesicle, pushing away the trophoblast cells. D. Embryo oniclepiblast forming a Hat disc on the surface of the blastodermic ‘. vesic e.

E. Inner cells mass, now embryonic knob. ec. Embryonic epiblast. en. Hypohlast. tr. Trophoblast.

ner to be indicated, despite the absence of yolk. Thus the situation differs from that found in previous forms, and particularly in the Bird, as follows: In the latter case the original archenteron consisted only of a shallow space between the hypoblastic roof and the underlying yolk. i The central region of the roof, later augmented by mesoderm, then folded off to form the gut, while the borders grew out and around the yolk to form the sac. In most Mammals, on the other hand, there is of course no yolk at all, so that the cavity of the blastocoel beneath the hypoblast may all, at first, be called archenteron. Later on the hypoblastic roof of this cavity now accompanied by mesoderm, and hence termed endoderm, folds of? as in the Bird to form a gut. Meanwhile the remainder of the cavity may or may not have become completely lined with endoderm. In the Guinea Pig for example only the roof is ever so constituted. In any event the part of this cavity not eventually occupied by the allantois, amnion and extra-embryonic coelom becomes the yolksac, with or without a ventral wall. In many cases, as in the Rabbit, Cat and Pig, this sac is fairly extensive, especially at first. In others, like most Primates, it is very insignificant. Certain special details and peculiarities of. these extra-embryonic structures will be considered later. Meanwhile it is to be noted that with the origin of the hypoblast the remainder of the inner cell mass together with the original subzonal layer may now be termed the epiblast. This epiblast is then further divided into that which composes the inner cell mass proper, now termed the embryonic knob, and that which composes the subzonal layer, now termed the trophoblast. It is to be noted that the latter completely encloses, for a time at least, the embryonic knob and the yolk-sac. Hence though originating differently, it occupies the same position as the chorionic ectoderm of the Chick (Fig. 255, A). In fact, with the mesoderm which in some cases later comes to line it, this layer constitutes the clwrion of the Mammal.


It is to be clearly understood that the process of gastrulation which has just been described is entirely one of delamination or infiltration, and proliferation; there is apparently no involution, invagination, nor epiboly, and hence also no concrescence. Consequently, it is not surprising that there is no well marked blastopore, at least in connection with the actual process of hypoblast formation. Later, as in the Chick, a primitive streak arises as a thickening in the epiblast, and again as in the Bird, parts of this streak are interpreted by many as the homologue of a blastopore. This will be discussed further when the origin of the primitive streak is described.

IMPLANTATION

By the time the stage described above has been reached, and some ' times somewhat earlier, the blastocyst has become attached to the uter ine wall. This process is known as implantation, and there are several methods by which it is brought about. It will be best, however, to postpone their detailed discussion until the description of the placenta is taken up. Sufiice it to say at this point that it is brought about largely by the activity of the trophoblast, aided by certain changes in the uterine wall itself.

THE AMNION

There are two chief methods by which the amnion is formed in the Mammal: ‘

I. The First Method of Amnion Formation.——-This method may be defined briefly as the method of amnion formation by folds. The


Fig. 256.-—Formation of the amnion in the Rabbit (Lepus). From Jenkinson (Vertebrate Embryology). After Assheton.

i.m. Inner cell. mass. Ll. Lower layer (i.e., hypoblast) . e.p. Embryonic plate (i.e.. blastoderxnal epiblast). R. Cells of Rauber. tr. Trophoblast.

first step in this method involves the transformation of the epiblast of the embryonic knob into a flattened plate overlying the hypoblast, the two layers being virtually homologous with the similar ones of the avian blastoderm. This flattening is accomplished, however, by two different processes. Thus though subsequent development of the amnion itself is similar, it is convenient upon the basis of the above differences in the initial stages to describe Method I under two headings, Type (a) and Type (b). « Method 1, Type (a) .-—-This type is illustrated by one of the Insectivores, T upaia (Fig. 255) ; in this animal a depression appears in the top of the embrvonic knob, and extends well down into it. The bottom of the depression then rises to the surface, and the edges are at the same time pushed apart. As this occurs the trophoblast cells above are broken and scattered. Thus the epiblastic plate of the blastoderm so formed comes to lie directly on the surface of the blastocyst.


Fig. 257.—DiEerentiation of the early Pig blastoderm. After Heuser and Streeter. A, B and C are from blastocysts measuring .6 mm. in diameter, and show clear differentiation of the inner cell mass (chiefly epiblast), and a thin layer of hypoblast, the whole being covered by a layer of trophoblast. D measured .8 mm., but does not show the hypoblast. The trophoblast over the inner cell mass is scattered, only two cells (cells of Rauber) remaining. '

‘ Method I, Type (b). —-— In this type, of which the Rabbit or the Pig form equally good examples (Figs. 256, 257), the process‘ is simpler, for here the knob merely flattens without the occurrence of any previous depression. In such cases after the flattening is completed, scattered trophoblast cells may remain for a time over the blastoderm, and are known as the cells of Rauber; these, however, soon disappeux. Subsequent Stages of Method 1, Types (a) and (b). —— As. suggested above it will now appear that the later stages of types (a)" and (b) are virtually alike. Before they are described, however, it should be noted that during or soon after the above processes, mesoderm has been proliferated between the epiblast and the underlying hypoblast in a manner to be described below. The two first layers may henceforth therefore be referred to as ectoderm and endoderm. Moreover, there has arisen within this mesoderm the usual coelomic split, separating it into the somatic and splanchnic layers. In either type (a) or (b), the amnion is then formed by folds of ectoderm and somatic mesoderm, which arise about the rim of the flattened embryonic knob (i.e., the blastodermal-ectoderm), in essentially the same manner as in the Chick (Fig. 258).



Fig. 258.—Diagrams of the formation of the embryonic membranes and appendages in the Rabbit. From Kellicott (Chardate Development). After Van Beneden and Julin (partly after Marshall). Sagittal sections. A. At the end of the ninth day, after coitus. B. Early the tenth day. C. At the end of the tenth day. Ectoclerm black; endoderm dotted; mesoderm gray.

al. Allantois. as. Allantoic stalk. b. Tail-bud. c. Heart. d. Allantoidean trophoderm (see page 543). e. Endoderm. ex. Exocoelom. f. Fore-gut. h. Hind-gut. m. Mesoderm. N. Central nervous system. p. Pericardial cavity. pa. Proamnion. s. Marginal sinus (sinus terminalis). t. Trophoblast. ta. Tail fold of amnion. v. Trophodermal villi. vb. Trophoblastic villi. y. Cavity of yolksac. ys. Yolk-stalk.


Thus as the amnion is completed by the meeting of the folds at the seroamniotir: connection, the chorion is at the same time re-established above it. This portion of re-established chorion now consists as usual therefore not only of an outer layer of ectoderm, but also of an inner layer of somatic mesoderm. Between the latter and the somatic mesoderm of the amnion is of course the extra-embryonic coelom.

There are, however, certain minor points of difference to be noted between the case of the Bird and that of the placental Mammal. In the first place there is the origin of the chorionic ectoderm. In the Bird this arises entirely from ectoderm of the extra-embryonic blastoderm which has grown out over the yolk. In the Mammal, on the other hand, since the folds arise just at the border between blastodermal ectoderm (embryonic knob) and trophoblast, a large portion of the ectoderm in the folds, i.e., that of the outer layer, seems to be formed from the latter substance. Thus_while the lining of the amnion may be chiefly blastedermal, the ectodermal part of the chorion which covers it is apparently entirely of trophoblast, a tissue which seems to have no real homologue in the Bird. A second but rather less important diflerence between Bird and Mammal is the fact that in the latter the tail fold often appears earlier than the head fold, and is therefore the longer of the two. In the Pig, on the other hand, head and tail folds are virtually equal, and are continuous with the lateral folds which arise coincidentally (Fig. 300).

II. The Second Method of Amnion Formation.-—In the second method of amnion formation, the trophoblast above the embryonic knob is never interrupted, a condition known as entypy. In contrast to Method I, the amniotic cavity then arises merely as a space within the embryonic knob or in connection with the knob and the trophoblast above it. Here again, however, there are variations in the process, so that it may best be described under the headings, Type “(a) , Type (12) , and Type (c). '

Method II, Type (a).——This type is illustrated by the Hedgehog (Erinaceus, Fig. 259) in which the rudimentary amniotic cavity appears, not in the knob itself, but as a space between the center of its dorsal side and the trophoblast. The edges of the knob, however, remain adherent to the trophoblast, and these edges now turn and grow toward one another between the trophoblast and the cavity. Thus when they meet and fuse, the epiblastic (future ectodermal) layer of the amnion is completed. Later, the extra-embryonic coelom lined by mesoderm forces its way in between the trophoblast (now chorionic ectoderm) and the epiblast, now ectoderm, of the amnion, so that in this manner the latter receives its mesodermal covering and the former its mesodermal lining. It may be noted that the type of amnion formation thus exemplified by the Hedgehog is quite similar in many respects to that just described under Method I, and may, therefore, represent a transitional stage between Methods I and II. Later, as the embryo develops, the edges of the flat blastoderm are folded downward in the usual manner, and portions of the mesodermal layers are of course involved in this process. The layer lying next to the endoderm is then splanchnic mesoderm, and the one next to the ectoderm (either trophoblastic or embryonic) is somati; mesoderm.


Fig. 259. -—Formation of the amnion in the Hedgehog (Erinaceus) . From Jenkinson (Vertebrate Embryology) . After Hubrecht. A. Early. B. Later stage.

am. Amnion. c. Extra-embryonic coelom. ec. Ectoderm. e.k. Embryonic knob. l. Lacuna. m. Mesoderrn. n. Notochord. tr. Trophoblast. y.s. Yolk-sac.


Method II, Type (b). — The second type of Method II is typically illustrated in the development of the Guinea Pig (Cavia), in which the process is as follows: _

Shortly after gastrulation is completed, the embryonic knob becomes separated from the trophoblast above it, and moves down near the opposite side of the blastocyst.‘’ In so doing, it pushes the central portion of the hypoblast layer before it; the edges of this central portion, nevertheless, remain attached to the dorsal trophohlast. This process presently results in the production of a clear space between the knob and the trophoblast, bounded on its sides by the upstretching hypoblast. A cavity now develops in the middle of the embryonic knob; this is the rudiment of the amniotic cavity (Fig. 260, A, B). On the floor of this cavity, the cells remain columnar, and are homologous with the upper


5 In this case and that of the Mouse and Rat the blastocyst, presumably be cause of its shape, has been termed by some the “egg cylinder,” though it is of course neither an egg nor a cylinder.


Fig. 260.—Fo1-mation of the amnion in the Guinea Pig (Cauia). From Jenkinson (Vertebrate Embryology). After Selenka. A. Early. B. Later. C. Latest stage.

a.tr. Allantoidesn trophoderm. o.tr. Omphaloidean trophohlast (see page 543) . l. Lacuna. e.k_. Embryonic knob. am.c. Amniotic cavity. y.s. Yo1k~sac hypoblast in A and B, endoderm in C.

or epiblastic layer of the embryonic portion of the blastoderm in previous forms. The cells of the roof and sides, on the other hand, soon flatten and form the epiblastic layer of the amnion. The latter now begins to expand, filling the space above it (Fig. 260, C). In the meantime mesoderm begins to arise between the epiblast of the hlastoderm ‘and the hypoblast beneath it. Thus the former becomes ectoderm and the latter endoderrn, while within the mesoderm the coelomic split occurs, producing two layers. These layers then spread out upon either side, the lower layer extending over the endoderm as the splanchnic mesoderm, and the upper layer extending up over the ectoderm of the amnion as the somatic mesoderm. The amnion is now completely formed, and consists, as in previous cases, of an" outer layer of mesoderm and an inner one of ectoderm. Further development merely involves an increase in

size and a gradual folding in about the embryo to form thenumbilical stalk. Fig. 261.—Formation of the amnion in the Mouse (Mus). From Jenkinson. ( Vertebrate Embryology). A.—E. Successiye stages. am. Amnion. am.c. Amniotic cavity. a.tr. Allantoidean nophoderm. c. Extra-embryonic coelom. e.k. Embryonic knob. l. Lacuna. l.l. Lower layer, L6. hypoblast. m. Mesoderm. m.g. Medullary groove. n. Notochord. a.tr. Omphaloidean trophoblast. py. dy. Proximal or upper, and distal or lower walls of yolk-sac. tr. Trophoblast. tr.c. Temporary trophoblastic or false amniotic cavity. y.s. Yolk-sac.


In anticipation of the method which is next to be described under type (c), however, it may finally be added that besides the amniotic cavity thus formed, there has also arisen a cavity in the dorsal trophoblast from which the knob was separated. This second space is often referred to as the false amniotic cavity, but in the type under discussion it never has any connection with the true cavity. It presently disappears and has no further significance.

Method 11 Type (c).—This last type of amnion formation is well shown in the Mouse (Mus, Fig. 261). In this form the embryonic knob moves down as in the Guinea Pig, pushing the endoderm before it, but does not become separated from the trophoblast. Instead, the latter simply thickens, thus filling up the space which would otherwise result. A cavity now appears in the upper part of the knob, and at once comes into communication with a cavity in the lower part of the thickened trophoblast, i.e., the false amniotic cavity. The mesoderm next arises between the hypoblast, now endoderm, and the epiblast, now ectoderm, of the knob, whence it spreads upward between the endoderrn and the thickened trophoblast. Within this mesoderm the coelomic split next develops upon either side, and the two coelomic spaces then press toward each other and finally unite. In this manner the mass of ectoderm and trophoblast, including the cavity, is cut in two in approximately the region where the ectodermal and trophoblastic elements were in contact. This process is such as to leave one closed cavity in the trophoblast and another closed cavity in the embryonic knob, with the extra-embryonic coelom lined by mesoderm between them. The cavity in the knob is, of course, the amniotic cavity with its usual layers, while the one in the trophoblast is the false cavity already referred to. The latter. it will be noted, is in no wise different from its homologue in type (b), except that in this case it temporarily communicates with the true cavity. Later, as in the former case, it disappears.

The Inversion of the Germ Layers. —— Before passing on to a discussion of the relative primitiveness of Methods I and ll, it is worth while to note a peculiar misconception which arose in the minds of early students of forms like Cavia and Mus. These are cases, it will be recalled, where the embryonic knob moves far down into the blastocyst. The obvious result is that the endoderm extends well up on either side, considerably above the level of the blastoderrn. Hence, if in examining the blastocyst of such a form, the investigator overlooked the outer layer of trophoblast, the first layer he would come to would be endoderm. He would thus get the impression that in some mysterious manner the endoderm


derm had gotten on the outside of the blastocyst. This oversight was exactly what occurred, and the phenomenon was, therefore, referred to as an “inversion of the germ layers.” As a matter of fact, it is now clear that no such inversion really exists, and hence the phrase is of only historical interest.



Fig. 262.—Graphic reconstructions of the Pig hlastoderm in the prestreak and early streak stages. After Streeter. A. Pre-streak stage. B. Early primitive streak, showing beginning mesoblast formation. C and D. Later stages in primitive streak development with greater extension of the mesoblast. As in the Chick, the mesoblast can be seen spreading out from the sides of the streak.

The Relative Primitiveness of Methods I and II. ——There has been some discussion as to which of these two main methods of amnion formation is the more primitive among placental Mammals, one view — that of Hubrecht— being strongly in favor of Method II. The reasons . for this attitude are based chiefly upon the characteristics of the mam malian chorion indicated in connection with Method I, and are as follows: In the Bird or Reptile (i.e., the Sauropsids) , there is, as suggested, no chorion (the layer corresponding in relative position to the mammalian trophoblast) until it is formed by the outer walls of the amniotic folds. In all the Mammals whose early development is known, on the ~‘ other hand, the blastocyst is entirely enclosed in trophoblast, or chtfiifi [, onic epiblast, before any amnion has been formed, either by folds or otherwise. It is true that in those cases where the process of folding occurs (e.g., in the Rabbit), the original trophoblastic chorion above the embryo virtually disappears, and the new one in this region is formed from the outer walls of the folds. Nevertheless, even in these cases there is no denying that there was a trophoblastic chorion previous to the


Fig. 263.--Later primitive streak and mesoblast formation in the Pig. After Streeter.

folding, and further that most of the (chorionic) portion of the folds is still really trophohlastic. Hence, as indicated above, it is said that the original trophoblastic chorion of Mammals cannot be regarded as homologous with the layer of the same name in the Sauropsids. From this statement it then follows, according to proponents, of this idea, that the cases of the formation of the mammalian amnion and chorion by folds could not have been derived from this process in the Reptiles; it must rather represent a reversion to the reptilian condition, or else a piece of independent evolution. 524 EARLY MAMMALIAN DEVELOPMENT

Fig. 264.——Surface view of two stages of the Pig blastoderm with parts of the adjacent blaslocyst. After Streeter. A. Primitive groove stage, length of blastederm about 1 mm. B. Blastoderm showing primitive groove and also beginning neural groove. length 1.7 mm. Crest of chorio-amniotic fold shows around margin of blastoderm. H.n. Hensen’s node (knot). N.gr. Neural groove. P.gr. Primitive groove.

There are, however, many zoologists who do not subscribe to the theory just presented. Instead they regard Method I as the more primitive, for the following reasons: In the first place it is known that Mammals as a class sprang from Reptiles, in which group the method of amnion formation is by folds as in the Birds. Furthermore, among those Mammals which are in other respects most primitive, i.e., the Monotremes and Marsupials, the formation of the amnion by folds (according to the evidence of those stages which are known in these animals) in all probability prevails. Lastly, as admitted by the opponents of the view now being presented, the trophoblastic ‘chorion of the Mammal is not really homologous with the true chorion of the Bird; it is rather a secondary developTHE PRIMITIVE S'l‘REAK 525

ment, whose early and complete enclosure of the blastocyst is made possible by the absence of yolk. Consequently, though the trophoblast usually takes a large part in the formation of the mammalian chorion, it has not, contrary to the argument stated in the foregoing paragraph, necessarily anything to do with the formation of the amnion. Indeed, as has been seen, the latter frequently forms by’ folds in spite of the presence of the precocious 3"; owpnajsgmue trophoblastic chorion, and

those cases where it does

not (Method II) are mere ly another secondary devel opment" In_ conclusion’ it Fig. 265.——Reconstruction of a surface view of may be Sald that 01’! the a Pig blastoderm, length 1.56 mm. After Streeter.

Heavy dotted line anterior to Hensen’s node is whole the lfrgurllents for the notochord. Cross hatched region is mesothe conception Just p1‘6- derm. Darkly lined area posterior to Hensen’s

sented appear to be rather node is remains of primitive streak.

more cogent and reasonable than those opposed to it and it is the one which is more widely held.

THE PRIMITIVE STREAK AND RELATED STRUCTURES

It will have been noted that during the process of amnion formation (in Method I, slightly preceding it) there arises in one way or another from the embryonic knob a flat plate of epiblast. This area of epiblast together with the hypoblast directly beneath it is the area from which the embryo proper is now to develop. As has been suggested, in the Chick it is termed the embryonic blastoderm; in the Mammal it is the embryonic disc.

The Primitive Streak and Groove. ——The primitive streak arises along the mid-line of the embryonic disc in what later proves to be the longitudinal axis of the embryo. The questions as to its source are very much the same as they were in the case of the Chick, but not so much experimental work has been done in an eiiort to answer them. The reasons for this are fairly obvious in view of the conditions under which the Mammalian embryo develops. However, careful study of fixed material has been made by Streeter and others in the case of the Pig, and


' Henserrs node 526 EARLY MAMMALIAN DEVELOPMENT

Fig. 266.-—A. Sagittal section through the embryonic shield of the Hedgehog, showing the transitory blastopore. From Kellicott (Chordate Development). After Hubrecht. B. Posterior part of a sagittal section through the embryonic disc of the Mole. C. Diagram of a sagittal section through the embryonic disc of the Mole. From McMurrich (Development of the Human Body). After Heape.

ant. Amnion. b. or bl. Blastopore. ce. Chorda endoderm. ec. Ectoderm. en. Endoderm. nc. Neurenteric canal. prm. Peristomial mesoderm. ps. Primitive streak. t. Trophoderm.

the following conclusions seem justified. There first.appears a thickened crescent of epiblast about what proves to be the posterior margin of the disc (Fig. 262, A). This crescent then assumes the form of an oval (Fig. 262, B, C ), and this gradually elongatesy into the primitive streak (Fig. 262, D; Fig. 263). Presently, as in the Bird, a primitive groove forms along the middle of the streak and at its anterior end there develops a thickened spot, Hensen’s knot (Figs. 264, 265) . It is to be particularly noted that in this knot there is likewise a pit which in some

Mammals, e.g., the Hedgehog, as in some Birds, temporarily opens into.

the archenteron (Fig. 266). In some others the pit merely pushes into THE PRIMITIVE STREAK 527

the notochord where it is known as the notochordal canal. In either case its possible homology with the part of the blastopore which in other cases forms a neurenteric canal is obvious, even though it disappears before the neural folds arise. Just what is going on during these changes of shape from a crescent, to a streak with a groove and knot, is not certain. It seems highly probable, however, that the process is again one of convergence of material toward the mid-line, and perhaps even some concrescence. Also as in the Chick, there is apparently rapid proliferation of cells in this region. The meanings of the groove and knot are no more or less clear than in the case of the Chick, and whatever their significance in that form they probably have the same significance in the Mammal (see below).

Origin of Mesoderm and Notochord. —-As in the Chick, so in the Pig, and presumably in other Mam primitive streak


ectoderm

mesoderm

x section pig blastoderm

mals, the streak is again the Fig. 267.—-‘Transverse section of one side of v

d a Pig blastoderm similar to one from which 5°urce Of the meso erm’ surface reconstruction in Fig. 262, C, was

which is proliferated from made. After Streeter. Long axis measurement . . of the blastoderm from which this section was its sides, and spreads out on

taken was .5 mm.

either hand and posteriorly

(Figs. 267, 268). Indeed as shown in Figure 262, this proliferation actually begins even before the streak primordium has assumed its definitive elongated form. Whether there is later any actual movement of cells through the streak from the upper surface, i.e., anything like infiltration (involution), as was suggested in the case of the Bird is not known, but it seems quite possible. If this were true it might help, again as in the Bird, to account for the development of the groove. Be that as it may the mesoderm having thus originated as a single sheet, very early begins to split into the usual somatic and splanchnic layers. This splitting starts in random isolated areas, thus producing small vesicles, which presently coalesce, to form more extenisve coelomic spaces (Figs. 262, 263). It willebe noted incidentally that the coelom first formed in this manner actually lies outside the definitely embryonic area, i.e., ap528 EARLY MAMMALIAN DEVELOPMENT

proximately the region comparable to the area pellucida of the Chick. Hence this first coelornic space is extra-embryonic, but very shortly it spreads within the embryonic region. Finally the notochord (headprocess) of the Pig arises according to Streeter (’27) as a rod of cells



“-‘9..3'.~‘4‘:-"W ,


Fig. 268.—A. Transverse section through the primitive streak of the Mole. B. Transverse section through a Human embryo of 1.54 mm. (Graf von Spee’s Embryo Gle.) From Minot (Laboratory Zfggt-Book of Embryology), after Heape (A), and Graf von Spee

ch. Notochord. ct. Somatic mesoderm of amnion. df. Splanchnic mesoderm. Ec. or ek. Ectoderm. en. or En. Endoderm. df. Dorsal furrow. g. Junction of extra-embryonic somatic and splanchnic mesvoderm. me. or mes. Mesoderm. p. Rudiment of embryonic coelom. p.gr. Primitive groove. Pr. Primitive streak.

proliferated at the primitive knot and pushed anteriorly. This it will be recalled is identical with one of the theories of notochord origin in the Chick. According to one of the most recent theories, however (Spratt, ’47) , the notochord in the Bird lengthens by growing posteriorly rather than anteriorly, as the primitive streak shortens. It is quite probable that whatever the true process proves to be in that case it will be found to hold also for the Mammal. However that may be, it should be noted that there is an interesting difference between the relation of the mesoderm and notochord in the Pig from that observed in the Chick. Thus it YOLK-SAC, ALLANTOIS, AND PLACENTA 529

will be seen that in the Pig the notochqrd has no mesoderm free area (proamnion) anterior to it as was true in the Bird (Fig. 265). The only suggestion of this occurs much earlier in front of the beginning primitive streak sometime before the notochord has begun to develop (Fig. 262).

The Nature of the Mammalian Primitive St-reak.——From the above ‘description it is very evident that the parts here indicated are virtually homologous with the similarly named structures in the Bird. Consequently if the primitive streak of the latter can be further homologizecl with the remains of an elongated closed hlastopore, it would appear that this homology holds equally well for the primitive streak of the Mammal. As previously suggested, however, because of practical

difliculties experimental observations on the behavior of materials dur-.

ing and immediately after the formation of the primitive streak are not as yet available in this instance as they were in the Chick. The chief evidence therefore arises from observation of the relations of the streak to the formation of the notochord and mesoderm already noted, and to parts of the future embryo. Thus in the latter connection it may be stated that the anus forms at the posterior end of the streak, and a. very marked pit, amounting in some cases to a virtual neurenteric canal, at its anterior end. '

In the case of the preceding topic as in others to follow the student who does not recall the comparable situation in the Chick is again urged to refresh his memory on the points in question, since we shall not repeat identical material. '

THE YOLK-SAC, THE ALLANTOIS, AND THE PLACENTA: THEIR STRUCTURE AND FUNCTIONS IN THE MAMMAL

Among the Amniotes of which the Chick is a type, i.e., the Birds, the. chief organs through which the embryo receives its nutriment and effects respiration have been seen to be respectively the yolk-sac and the allantois. Among the vast majority of the Amniote group known as Mammals, however, these organs are very largely, and in many cases completely, supplanted in these functions by a new structure, typically associated with the allantois and termed the placenta. The large group of Mammals among whose members this organ is most fully developed is therefore known as that of the placental Mammals, a group which hastalready been frequently referred to. It will presently appear, however, that within this group there are certain types of placentas which vary from one another, ‘both in their structure, and in the degree to 530 EARLY MAMMALIAN DEVELOPMENT

Fig. 269.—Fetal membranes of A, Monotremata; B, C, D. Marsupials. B. Phalangista, Aepyprymnus, Didelphys, Bettongid; C. Dasyurus; D. Perameles and Halmaturus. (In Didelphys the proamnion persists as in Dasyrus.) From Jenkinson (Vertebrate Embryology). (A, B, D, after Semon; C, after Hill.)

In this diagram of Mammalian fetal membranes the trophoblast (ectoderm of mammalian chorion) is stippled, the ectoderm oi the amnion represented by a continuous line, the endoderm by a broken line, and the mesodertn (somatopleure and splanchnoplenre) by a thick line swollen at intervals.

all. Allantols. am.c. Amniotic cavity. pr. Proamnion, i.e., portion of amnion without mesoderm. y.s. Yolk-sac. s.t. Sinus terminalis of area vasculosa.

which they have assumed the place and functions of the allantois and the yolk-sac‘. There exist also two relatively small mammalian groups, the Monotremes and the Marsupials, whose members possess either no placenta at all or only a very rudimentary one. Under these circumV or F‘ stances, therefore, it appears most convenient to treat the subject by i taking up the conditions of the above organs in one group at a time. The Monotremes and the Marsupials will be considered first, since they are most primitive, and exhibit a condition most nearly akin to that in the Reptiles and Birds. After these there will be discussed certain orders of truly placental Mammals which best illustrate the various types

noes-2 ax:

‘ma. THE MARSUPIALS 531

of allantoic placenta, and perhaps suggest its method of evolution. The orders to be thus considered are the Ungulazes, the Carnivores, the Rodents, and the Primates. Finally before passing to a study of the first group, it may be mentioned incidentally that the discussion of this subject also necessarily involves in each case a more extended reference to the matter of implantation referred to above.

THE MONOTREMES

These curious mammalian forms comprise the Spiny Ant Eater (Echidna) , and the Duck Bill (0rnithorhynchus) . They are remarkable as Mammals in that they lay hard-shelled eggs like Birds. As might be expected in such a case, the yolk—sac is well developed and illed with yolk, while the allantois is also prominent. The placenta, on the other hand, because of its peculiar nature and functions, which its study will presently reveal, is naturally entirely lacking. In short, in eggs of this sort the embryonic parts under discussion are in all respects characteristically reptilian or avian (Fig. 269, /1)-.

THE MARSUPIALS

This group comprises the Kangaroos (Macropodidae), the Opossums (Didelphyidae), the Marsupial Cats (Dasyuridae) and the Bandicoots (Peramelidae). These animals are all characterized by the fact that their young are born in a comparatively undeveloped condition. They then crawl inside of the Marsupial pouch of the mother and become attached to her teats, where they remain for some time. As might be expected under such circumstances, the means for obtaining nourishment and aerating the blood previous to birth are very primitive. In fact, among the various members of the group there occur some very excellent examples of graded transition from the condition in the Monotremes to that in the real placental Mammals. The Opossum is per» haps as primitive a form as any in this respect, and will therefore be considered first.

The Most Rudimentary Type of Placenta. -—ln Didelphys, or the Opossum (Fig. 269, B), the yolk-sac, as in all the Marsupials, is well developed though it contains no yolk. Nevertheless, upon its upper surface there is a clearly defined area vasculosa, bounded by a sinus terminalis. Since there is no yolk, however, the nutriment which the above area is to convey into the embryo must be obtained from some other source; this is accomplished in the following manner: Although 532 EARLY MAMMALIAN DEVELOPMENT

the mesoderm, and consequently the area vasculosa, do not reach to the opposite side of the yolk-sac, the endoderm on that side comes into contact with the trophoblast of the blastocyst. During implantation this trophoblast becomes thrown into folds (not shown in the figure) which fit into depressions in the uterine wall. The latter then secretes a viscid fluid, the uterine milk, which is absorbed via the trophoblast and endoderm, and finally reaches the embryo, partly at least by way of the area va.sculosa.- This contact of the embryonic trophoblast and the uterine tissue may be regarded as a very primitive beginning of what will later berecognized as a placenta. The allantois is very small in this case, as in most other Marsupials, and has no contact with the trophoblast. The

exact means by which the embryonic blood is aerated, therefore, is a '

little uncertain. Very possibly, however, it also is accomplished through the contact of yolk-sac and maternal tissues.

A “ Yolk-Sac Placenta.” —-— Dasyurus is the second form to be considered, because it exemplifies the next step in the development of a true placenta (Fig. 269, C). The allantois, however, is still small, and the placenta-like structure which occurs is, therefore, again associated entirely with the yolk-sac. Furthermore, the trophoblast in contact with the non-vascular area of the sac once more forms the connection with the uterine wall. In this instance, however, this implantation is more thoroughgoing, and there appears for the first time that process ‘of uterine erosion so noteworthy among some of the higher forms. This erosion is accomplished by the trophoblast which, after becoming thickened and syncytial (i.e., trophodermal) in certain regions, eats into the uterine epithelium and engulfs some of the maternal blood vessels. The blood so obtained passes in between the trophoblast and yolksac, secretions from one or both of which digest it so that it can be absorbed. Presumably also such an arrangement makes possible respiratory exchange of gases between embryonic and maternal blood. The type of contact which is here illustrated is so intimate that the area in which it occurs is sometimes referred to as a yplk-sac placenta.

A Primitive “ Allantoic Placenta.” —-— Finally, the most advanced condition in this Marsupial series is illustrated in Perameles, where the following situation occurs (Fig. 269, D) : Here the yolk-sac is again large, and possesses an area vasculosa which is probably functional in absorbing some nourishment by way of the trophoblast. In this case, however, the allantois also is well developed,vand comes into contact with the mesoderm of the chorion. Implantation then occurs and the trophoblast in the area of this contact becomes attached to the uterine — ‘-, i

THE PLACENT-ALIA 533

wall, whose epithelium in this region is transformed into a vascular syncytium. The trophoblast finally disappears, and the maternal blood vessels come into intimate contact with those which have grown out through the mesoderm of the allantois (Fig. 270). Thus there is established a true allantoic placenta. As will presently appear, however, the exact relationship of its embryonic and its maternal parts is different from that described in any of the subsequent types.

4/


f. b. v.

73. mt. Fig. 270.——Section through the placenta of Perameles. From Jenlcinson (Vertebrate Embryology). After Hill.

all. Allantoic epithelium. m. Mesoderm of allantois together with xnesoderm of chorion. f.b.v. Fetal blood-vessel. ep.s. Syncytium of uterine epithelium. m.b.v. Maternal blood-vessels. c.t. Sub-epithelial connective tissue of uterus.

In connection with this, the first real placenta to be noted, there is one very important fact to be pointed out. Neither in this placenta nor in those of any other type does the fetal and the maternal blood actually mix. It is always completely separated by one or more membranes. Through these membranes, however, it is easily possible for an exchange of nutritive and waste materials, as well as gases, to take place.

This-completes the account of the Marsupials, and we are now prepared to pass on to the orders of the genuine placental Mammals. As has been indicated, the latter are so named because here an allantoic placenta of one sort or another becomes the usual and chief means of embryonic nutrition and respiration. In the Marsupials, on the other hand, such a condition occurs only in the single instance last cited. '

THE PLACENTALIA OR TRUE PLACENTAL MAMMALS

Within this large group, the embryonic appendages whose condition is being considered are probably in their-most primitive form among 534 EARLY MAMMALIAN DEVELOPMENT

the Ungulates, and this ‘order, therefore, will be treated first with special reference to the Mammal; we have selected for later detailed study,

the Pig.

The Ungulates (the Pig). The Early Means of Nutrition and the Yolk-Sac. —- Before the blaste cysts enter the horns of the bicornate uterus, the latter have been prepared for their reception during the pro-oestrum, oestrus and early


Fig. 271.—Diagram of a fetal and maternal cotyledon of the Cow. From Jenkinson (Vertebrate Embryology).

all. Allantoic epithelium. tr. Trophoblast. 11. Villus. ep. Uterine epithelium continued into crypt. c.w. Wall of crypt. The maternal conneco live tissue is shaded.

dioestrum periods as explained in cohnection with the oestrus cycle. As a result of this the uterine walls are thickened, and their glands hypertrophied to produce the secretion (uterine milk) which helps to supply the embryos with nutriment and is eagerly absorbed by the trophoblast of the blastocysts. Meanwhile gastrulation has occurred, the endoderm (hypoblast) has grown around the inside of each blastocyst, and thus with the advent of mesoderm and the folding off of the gut, an empty yolk-sac is established in each. It is relatively large, and in the early stages possesses a well developed area vasculosa. Thus it is able to function actively in passing nutriment from the uterine cavity into the embryo. Later, however, the yolk-sac becomes insignificant, its function being entirely taken over by the allantois and the placenta, whose development will now be described. '

The Placenta arid the Allantois.—The blastocyst of this group, it will be remembered, soon becomes greatly elongated, reaching a length 1 1 i I I I

THE PLACENTALIA 535

of as much as a meter. It is not, however, to be understood from this that it is actually extended to this extent, for if it were it would be longer than the uterine horn in which it and several of its fellows are contained. Instead, as the threadlike blastocyst of the Pig grows, it becomes greatly folded, the folds fitting into corresponding folds of the

blastodermic vesicle amnion ¢mb")'°


l‘ I horlonlc crophoblast


diagrammatic x section r of blastodermlc vesicle _.- '


Fig. 272.—-Drawing of a Pig blastodermic vesicle measuring about 350 mm. in length and 4-0 mm. in diameter, and a diagrammatic :ransverse section of same. The contained embryo measured about 40 mm. in length. Note the folds which replace the villi of many Ungulates.

uterine walls. Later when the embryo develops and the blastocyst expands, the latter is very much dilated and shortened, after which the term blastodermic vesicle is more commonly applied to it. As the vesicles reach their maximum length on about the thirteenth day. their trophoblast has become relatively adherent to the uterine epithelium, and implantation is said to have occurred.’ In the case of the Pig the surface of the endometrium remains folded as does ,the surface of the

7 The implantation time varies in difierent animals, but in most of them it occurs within a few days, often about seven, after the blastocysts reach the uterus. In a few cases, however, implantation may be markedly dela'yed. Thus in the Long

Tailed Weasel and the Martin the blastocysts are said to lie dormant in the uterus for many weeks (Wright, '42). - 536 - EARLY MAMMALIAN DEVELOPMENT

blastocyst, though not to the extent that it was at its greatest length. This arrangement of course increases the area of trophoblastic and uterine contact through which the exchange of nutriment and excretory products can occur. This capacity for exchange is still further augmented by the fact that in certain spots (areolae) microscopic projections (villi) push out from the chorion into small spaces between the latter and the uterine epithelium. These spaces are filled with the uterine secretion referred to above. In some Ungulates such as the Cow, the villi

atrial part posterior ardinti vein



ventricular area . temporary viteiime and intcstlnai arteries


Fig. 273.——A 6.2 mm. Pig embryo (23 somites), injected, showing the circulatory system and beginning allantois. After Sabin.

are larger, and arranged in bunches or cotyledons, while the corresponding areas in the uterine wall with which the cotyledons come into contact are called caruncles. These latter are permanently located, and are said to exist as raised areas even in the uterus of the unborn calf. Thus in these instances the locations of the embryonic cotyledons are secondary, being determined by the positions of the maternal caruncles.

Meanwhile, to return to the Pig, by the time the embryo has reached a length of 4-6 mm. the allantois has begun to outstrip the yolk-sac, and soon comes to occupy the major part of the extra-embryonic space. It appears first as a rather conspicuous crescent-shaped outgrowth encircling the posterior of the embryo, with its -horns extending anteriorly (Fig. 273). In this respect it difl'ers considerably from the Chick allantois which it will be recalled is first noted as a roundish bladder pushing anteriorly and upward to the right from beneath the curled tail. The crescentic allahtoic outgrowth of the Pig rapidly works its way around the amnion, pushes aside the now useless yolk-sac, and eventuTHE PLACENTALIA 537

ally extends everywhere throughout the extra-embryonic space of the vesicle except in the extreme ends (Fig. 272). The mesoderm which covers the allantois carries the umbilical blood vessels, and this mesoderm together with the capillaries of the vessels becomes closely adherent to the mesoderrn of the chorion into which these capillaries penetrate. In this manner the fetal vessels come close enough to those of the uterine mucosa for the necessary exchanges to occur. Thus is constituted the Ungulate (in this case Pig) placenta, which as will be noted, comprises almost the whole surface of the blastodermic vesicle.

It is to be especially noted that in the processes just described there is absolutely no erosion of the uterine epithelium.‘ Instead the chorionic folds simply fit in between those of the endometrium from which they may be easily stripped away at any time. Indeed during gestation the endometriumicontinues to secrete nutritive substances between itself and the chorion. This is absorbed by the latter and taken up by the embryonic vessels, so that in this case, as in some others, the embryonic nutriment is not all obtained directly from that which is carried in the maternal blood. A placenta in which the contact. between fetaland maternal tissue is such as indicated is often defined as indeciduate. This term implies that at the time of parturition, the wall of the uterus is literally not deciduous. That is, there is no tearing away of maternal tissue when the fetal part of the placenta separates from that of the mother.

In concluding this discussion of implantation in the Pig a curious fact may be noted which apparently applies also to other Mammals which have two horned uteri and produce litters. Thus it is well known that the number of eggs ovulated by the two ovaries may be quite unequal as indicated by the corpora lutea present. Yet Corner has demonstrated that the number qf embryos developing in each uterine horn is practically the same. This can only mean that enough of the embryos from the side which produced more eggs have migrated to the opposite side to equalize the numbers in the two horns. How this is brought about no one knows, but in the case of the Pig it apparently occurs previous to the elongation of the blastocysts.

The Carnivores. The Yolk-Sac. —As in the Ungulates, the period of the pro-oestrum results in the accumulation within the uterine hornsof a nutritive mix 3 According to some authorities there is erosion of the inaternal epithelium in the Ruminants. 538 EARLY MAMMALIAN DEVELOPMENT

ture somewhat similar to that already described. In some cases, however (e.g., the Cat), it appears to be less abundant than in the Ungulates, and of a more watery consistency. The uterine mucosa is of course also hypertrophied in the usual way, and everything is ready for the


Fig. 274.-——Fetal membranes and placenta of the Dog. From Jenkinson (Vertebrate Embryology). After Duval. '

all. Allantois. am.c. Amniotic cavity. In. Mesometrium, or sheet of connective tissue attaching the uterus to the body wall. pl. Zonary placenta. (See text under description of the placenta of the Carnivores for the definition of this term.) y.s. Yolk-sac. The fetal mesoderm, connective tissue and blood-vessels are in black.

reception of the blastocyst, which in this instance is oval, never at any time threadlike. Again the latter begins its development by absorption of the nutrient fluid. A yolk-sac has meanwhile developed, in_ the usual Mammalian manner, and apparently it plays about the same part in this process as was noted in the Ungulates. As in that order, also, this appendage later becomes relatively insignificant (Fig. 274) .

The Placenta and the Allantois. —— While these events are occurring, 3. change is taking place in the uterine wall. In a band which completely encircles this wall the epithelium disappears. Likewise, in the THE PLACENTALIA 539

‘7‘;;-~;-‘'7‘/=‘7‘-—--— 8"’:/’ %g___,.

tr.

rn.b.c.

f. c. t. f. b. c.

In .b.v.

Fig. 275.—Section through the placenta and uterine wall of the Cat. From Jenkinson (Vertebrate Embryology). all. Epithelium of allantois. f.b.v. Large fetal bloodvessels. f.b.c. Fetal capillaries. f.c.t. Fetal connective tissue. tr. Trophoblast (finely shaded). m.b.c. Maternal blood capillaries; these are immediately surrounded by maternal connective tissue (coarsely stippled). m.b.v. Maternal blood-vessels passing through the maternal glandular tissue (d). cp. Compacta (necks of glands). sp. Spongiosa (dilutions of glands).

region of a corresponding band about the equator of the oval blastecysts, the latter begins to adhere to the prepared uterine wall. During this process of implantation, trophoblastic villi similar to those of some of the Ungulates begin to develop from the wall of the blastocyst in the region of its adherence. Because of the obvious band or zone-like

shape of this region, the type of placenta which develops in this order A

is called zonary. The villi of the chorion, which may contain a core of 540 EARLY MAMMALIAN DEVELOPMENT

mesoderm, now push their way directly iillio the mucous tissue of the uterus. As they do so, they absorb any remaining epithelial debris which comes in their way. In this manner, they soon.become firmly embedded in the maternal tissue and surrounded by maternal blood vessels. While this is going on, the allantois has grown out, and as in the Ungulates, soon becomes the chief appendage of the embryo. When the allantoic mesoderm comes into contact with the chorionic mesoderm in the zone of implantation, the allantoiccapillaries penetrate the villi, and the placenta is virtually complete. During subsequent development, however, it becomes thickened somewhat by growth and branching of the villi and capillaries, and also of the maternal connective tissue in which they are embedded. The glands of the latter continue to supply debris and fat, which is absorbed by the chorionic villi up to the end of gestation. The main source of embryonic nutrition, however, is presumably material contained in the maternal blood (Fig. 275).

It will be noted that the attachment of the fetal and the maternal parts of the placenta is much more intimate in this case than it was in the Ungulates. This has resulted from the disappearance of the uterine epithelium, which allows the capillaries in the fetal villi to come that

much nearer to those of the mother. Because of this very close attach-.

ment, it also happens that at birth a large portion of the maternal tissue is torn away with the fetal portion of the placenta. For this reason, this type of placenta may be regarded as deciduate. Indeed, as will appear from a study of the remaining groups, the Carnivores are probably the only animals possessing a placenta of which this is true in any large degree.

The Rodents.—-As in the forms previously studied, the uterine epithelium of the horns is in, a hypertrophied condition following the proioestrum and oestrus, and is thus ready to receive the blastocysts (“ egg cylinders ”) when they reach the uteri. The method of attachment and of placenta formation which now follows varies somewhat in different Rodents, although it is fundamentally similar in all of them, and leads to practically the same results. It will further be found that in this case, the former process, i.e., attachment or implantation, is somewhat elaborate, and therefore requires more detailed attention than has hitherto been necessary. The chief conditions with respect to this process as well aslto the general character of the yolk-sac, may be illustrated by reference to two forms, the Mouse and the Rabbit. _

Implantation and the Development 0/ the Yolk-Sac. —— In the case of the Mouse, each elongated uterine horn becomes lined with pits upon its anti-mesometric side. This is the side opposite its point of attachment to r_

THE PLACENTALIA 54.1

the coelomic wall, the latter region being termed the mesometric side. Each of the ovoid blastocysts, of which there are several in the -Mouse, becomes embedded in one of these pits with the embryonic knob facing the narrow lumen of the uterus (Fig. 276, B). That this anti-mesometric


Fig. 276.—-Five stages in the formation of the placenta in the Mouse. From Jen» kinson (Vertebrate Embryology). A. The blastocyst free in the uterus. B. The blastocyst attached and the placental thickening of the developed allantoidean trophoblast (trophoderm) (a.t.r.). C. Later stage, after closure of the amniotic cavity (am.c.) and the obliteration of the uterine lumen. D. Placenta becoming established, and reappearance of uterine lumen (l’u-.). E. Elaboration of the placenta. l()isap)pearance of the distal wall of the yolk-sac and omphaloidean trophoblast 0.tf. . c. Extra-embryonic coelom. l'u. New uterine lumen on the anti-mesometric si . lu. Original lumen of the uterus. y.s. Yolk-sac. ;v.st. Yolk-stalk. u.c. Umbilical cor m.. Mesometrium.



implantation is not the result of gravity has been clearly demonstraf in the Rat by Alden (’45). He cut out the middle portion of a uter '‘ horn, leaving blood vessels intact, and replaced it in an inverted « . tion. Implantation in this section was still on the anti-mesometric,‘; now dorsal, side. Continuing with the case of the Mouse the furth tory of a single blastocyst will suflice. ’ ..

As soon as the embedding has occurred, the trophoblast imm N starts to erode the epithelium of the pit, and to devour the debris ' 542 EARLY MAMMALIAN DEVELOPMENT

results. Meantime the blastocyst enlarges sufliciently so that the side containing the embryonic knob crosses the uterine lumen and comes in contact with the opposite wall (Fig. 276, B, C). In this way, each blastocyst obtains attachment at every point, and completely obliterates the cavity of the‘ ‘uterus where it is situated. At every place where contact is thus

97- am.

Fig. 277.--Fetal membranes and placenta of the Rabbit. From Jenlrinson (Vertebrate Embryology). After Duval and Van Beneden. pr.am. Proamnion. Other letters as in Fig. 276.

established, i.e., on the bottom and sides of the original pit, and also upon the uterine wall opposite to it, erosion of the uterine epithelium is carried on. The placenta, which will presently he described, is established on the mesometric side of the uterus at the second point of contact, and therefore next to the embryo. Then, owing to the intimate relation of trophoblast and allantois in this region, the thickened trophohlast (trophoderm) on this side of the blastocyst is called allantoideon. On the opposite side, i.e., at the original bottom of the pit, the uterine lumen is later again established. Here for a while epithelium once more develops, and covers both the wall of the uterus and the blastocyst (Fig. F______ _. .. .Hhm_a_

THE PLACENTALIA 543

, 276, D). Inside the latter, the yolk-sac has meanwhile formed, and on its 3 upper surface has acquired an area vasculosa. Its lower wall, on the other hand, which is in contact with the trophoblast of the blastocyst, finally degenerates. The trophoblast (in this region termed omphaloidgun) and the newly formed epithelium at this point then also vanish, and thus the interior of the yolk-sac is placed in immediate communication with the re-established uterine cavity (Fig. 276, E) .9

Tufning now to the method of implantation in the Rabbit, it is found to be somewhat less complicated. Here a pair of folds arise upon the mesometric side of the uterus, and the blastocysts become attached to these. Each blastocyst in this case lies between the folds and becomes i attached by the trophoblast on either side of the embryonic disc. In 3 these regions, the uterine epithelium is eroded, and two placentas are established which later merge into one (Fig. 277). The opposite side of the blastocyst forms no intimate contact with the uterine wall and presently disappears. Concurrently the ventral wall of the yolk-sac also disappears, so that again, as in the case of the Mouse, the cavity of the sac x is directly continuous with that of the uterus (this stage not shown in the figure).

Having thus described the two chief types of implantation among the Rodents, we are now in a position to discuss the nature of the placenta and other means of nutrition common to all this group.

The Placenta and the Allantoi.s.———During the erosion of the uterine epithelium indicated above, the allantoidean or placental trophoblast becomes greatly thickened, to form trophoderm. This trophoderrnthen continues to eat down into the mucous layer of the uterine wall, engulfing, as it does so, maternal blood vessels, together with glycogen from the glycogen-filled cells (maternal glycogen tissue). There next appear in the trophoclerm numerous lacunae, and into these is emptied the maternal blood from the vessels whose walls have been destroyed (Fig. 278, A). Meantime an allantois has arisen. In the Rodents, the endodermal portion of this organ containing the cavity is usually small, although in the Rabbit, which in this as in most other respects is more primitive, the allantoic cavity attains a considerable size (Fig. 277). The mesodermal part, however, is always well developed, and soon reaches the trophoderm of the placental region, bringing with it the umbilical blood vessels (Fig. 278, B). The capillaries of these vessels then

” The assumption has been that in this as in other cases the vascularized wall of the empty yolk-sac functions in obtaining nutrimc.-nt for the early embnyo. Recent

experiments on the Rat. however, involving the tying 03 of‘ the vitelline vessels.

seem to indicate that such a function is negligible, at least in this animal (Noer’47). 544_._ EARLY MAMMALIAN DEVELOPMENT


a. m. f. b. v.


\\\\

vs‘ \§.\ .\

it

\\\\ ( ‘ .t\\\ r ‘~" ‘L


Fig. 278.—Placentation of the Mouse. Details of the five stages of Fig. 276. From Jenkinson (Vertebrate Embryology».

A. Strip of a section through the allantoidean trophoblast (trophoderm) and overlying maternal tissues in stage C, Fig. 276.

a.t.r. Allantoidean trophoderm. mu. Muscularis. m.v. Maternal bloodvessel, opening below into I. lacunae of the trophoderm. Lu. Original lumen of the uterus. m.g.c. Maternal glycogen tissue.

B. Similar strip of the same parts in stage D, Fig. 276.

_ fjmv. Fetal blood-vessel. a.m. Allantoic mesoderm. Other letters as in .

C. Similar strip of the last stage, Fig. 276.

tr.g.c. Trophodermal glycogen tissue. Other letters as in 3.

Note that ,ultimately this placenta is very largely composed of trophoderm, which is a non-maternal tissue. Hence, since at parturition the line of separation passes through the placenta (the trophodermal glycogen tissue), little or no maternal tissue is lost, and the placenta is essentially indeciduate. (See text.) l

THE PLACENTALIA 545

penetrate the trophoderm so as to come near to the cavities containing the extravasated maternal blood. This blood is being constantly poured into the central space of the placental region, and withdrawn at the periphery through the maternal veins. Gradually, toward the maternal side, the trophoderm surrounding the lacunae becomes further vacuolated through the secretion of glycogen, thus establishing a trophoder. mal glycogen tissue (Fig. 278, C). Eventually through the increase of the latter, the layer of original maternal glycogen tissue is entirely eliminated.” Such is the character of the completed placenta of the Rodents, which, because of its development upon only one side of the blastocyst, has the general shape of a disc or button. It is, therefore, termed discoidal, as distinguished from the zonary form found in the Carnivores.

Comparing the placenta in this case with that noted in the Carnivores, the chief difference will be found to be that, in the completed organ of the Rodents, maternal tissue plays very little part. The placenta indeed is principally composed of the fetal trophoderm with its capillaries, lacunae, and glycogen tissue. This difference seems to be achieved by the fact that the trophoderm erodes not only the uterine epithelium, but a large part of the mucosa and its blood vessels as well. Because of this peculiar structure, it happens at parturition that, aside from the blood in the lacunae, very little real maternal tissue is lost. This follows from the fact that the actual line of separation runs through the region of vacuolated cells which have now lost their glycogen and collapsed, and this region, as noted, is held to be entirely trophodermal. On account of this lack of maternal tissue to be torn away, many authorities regard the term deciduate as a misnomer when applied to placentas of this type. If the above description be correct, it apparently is a misnomer. Nevertheless, such placentas are still commonly classified under this head.

As regards the method of nutrition in this order, it is apparent that, aside from the glycogen, nutriment is chiefly obtained, so far as the placenta is concerned, from the maternal blood. It will be remembered, however, that among the Rodents, the yolk-sac is always eventually open to the uterine cavity. Thus, for instance in the Mouse and the Rabbit,

the lower epithelial wall of this organ was found to disappear com- ‘

pletely, while in the Guinea Pig it is never even formed. This being the case, the upper wall of the sac may, in’ some cases at least, function throughout gestation in the absorption of uterine secretions. To the ex 1° The maternal glycogen tissue is said to be more abundant and persistent in the Rabbit. 546 EARLY MAMMALIAN DEVELOPMENT

Fig. 279.——Diagrams illustrating the formation of the umbilical cord and the relations of the allantois and yolk-sac in the Human embryo. From McMurric_h (Development of the Human Body). The heavy black line represents the embryonic ectoderm; the dotted line marks the line of the transition of the body (embryonic) ectoderm into that of the amnion. Shaded areas, mesoderm.

Ac. Amniotic cavity. Al. Allantois. Bc. Exocoelom. Bs. Body-stalk. Ch. Chorion. P. Placenta. Uc. Umbilical cord. V. Chorionic (tropho dermal) villi. Ys. Yolk-sac.

tent that this is true, therefore, the Rodent yolk-sac, both in its form and in its activity, differs markedly from the types previously studied within the strictly placental group.

The Primates.“ The Allantois and the Yolk-Sac. —— In the order of Primates, the nature of the yolk-sac and allantois is somewhat unique, while the latter

11 The characteristics of the embryonic appendages which are ascribed to this order apply to only'une of the family of Lemurs, i.e., Tarsius. This animal, in respect to these organs, may be classed with the lower Monkeys. So far as is known, however, all other Lemurs are similar to the Ungulates as regards the yolk-sac and allantois, and also even in the possession of a difluse indecidiiate placenta. This exception must be home in mind with reference to all statements concerning the Primates as a whole. THE PLACENTALIA 547



Fig. 280.——Diagrams of sagittal sections through the Human blastoderrnic vesicle, showing the formation of the amnion and trophoderm. From Kellicott (Chardate Development). /1-D, after Keibel and Elze. E. From McMurrich (Development of the Human Body), after Graf von Spec. In all the figures the anterior end is toward the left, and in all the figures except E the following conventions. are used: Black, embryonic ectoderm: heavy stipples, trophoblast and trophoderm; light stipples, endoderm. Ohlique ruling, mesoderm except in A. A. Hypothetical early stage; oblique ruling represents magma reticulare (see text). 8. Amniotic cavity and wide exocoelom established; endoderm limited to a small vesicle beneath the embryonic ectoderm. The exocoelom in reality contains scattered mesenchyme cells. C. Blastodermic vesicle enlarged and covered with trophedermal villi, into which’ the mesoderm is extending. Endodermic vesicle (yolk-sac) very small (stage of Peter’s ovum). D. Embryonic portion only, of an older vesicle showing the neurenteric canal, primitive streak (in the plane of the section posterior to canal), and body-stalk. The mesoderm of the yolk-sac is becoming vascular. E. %;a;gi)ttal section through a Human embryo of 1.54 mm. (Graf von Spec’: embryo

C a. Amniotic cavity. at. Allantois. am. Amnion. B. Body-stalk‘ (umbilical cord). ch. Chorion. e. Exocoelorn. nc. Neurenteric canal. V. Chorionic villi. Y. Yolk-sac. y 548 EARLY MAMMALIAN DEVELOPMENT

organ is also peculiar in its method of development. An account of these structures will be given, therefore, before proceeding to the matter of implantation and placenta formation within this group.

First, as regards the allantois, it will be found that the endodermal sac is even more limited than it was in the majority of the Rodents. Furthermore, the mesoderm of that organ does not comprise, as in most


Trophcblosl‘

.. Ex traembryonic

mesoblusi Pfimmve Exccoelo "c cndodmn ,,,,,,,,,,;“,;

Extrcemrycmc mdoderm Uterus ring,“ 5"," db“ Trophoblufl mesoblast Amnion Gerrfldigk


xh-cembryonic ‘"‘l°d"’"‘ mesobtast


E 1 A Primitive ",:.::ni,:::. endodtrm

Fig. 281.—Mid-sagittal sections through four Human blastocysts (“ ova") and surrounding uterine wall. After Hertig and Rock. A and B are estimated as 11 days old plus, while C and D are estimated as 12 ‘days old plus. B is the Miller “ovum,” while D is the Werner (Stieve)

previous cases, a mere covering for the sac; instead, it forms a thick stalk, the body-stalk, or umbilical cord, which attaches the embryo to the chorion or wall of the blastocyst. Into the proximal end of the mesoclermal cord, the hollow endodermal element then projects for only a short distance (Figs. 279 and 280). This condition is brought about as follows:

From what is known of the earliest human embryos (7-15 days, see i ‘ below I} the blastocyst, following cleavage and gastrulation, contains the § _ following structures and materials. First there is the blastoderm, con” E ‘ sisting of a layer of ectoderm and endoderm with a small amniotic cav; ity derived appariantly from a split in the embryonic knob (Method II, Type b, seeahove): Second, the greater part of the blastocoelic space is

,Ԥ THE PLACENTALIA 54,9

occupied by a reticulate material, the magma reticulare, which probably consists of coagulated protein containing fluid. Scattered through this reticulate substance, and lining parts of the trophoblast, are a few mesoderm cells ':(extraembryonic mesoblast) presumably derived from the blastoderm L,‘( Fig. 281, A, B). At about the center of the blastocyst in these human specimens there occurs a particularly definite space

bou_nded laterally and ventrally by an especially clearly defined layer of the reticulum, termed the exocoelomic membrane or Heu.ser’s mem Remnant exocoelamic membrane


Fig. 282,-Mid-sagittal section of a Human blastocyst and surrounding uterine wall with an estimated age of 15 days, the Edwards-.lones-Brewer “ovum.” After Hertig and Rock.

brane (Fig. 281). Dorsally this space is lined by the endoderm of the

blastoderm, and it has therefore been interpreted by some as the yolk— '

sac. Others maintain that the true yolk-sac does not appear until slightly later, about the 13th day. It is difiicult, however, to distinguish the

_ “endoderm” of this later yolk-sac from the exocoelomic membrane

bounding the central “ exocoelomic space ” of the earlier embryos. At all events in these later stages the magma reticulare has mostly disappeared and the trophoblast is lined by a definite layer of mesoderm. This also extends around what is now termed the yolk-sac, up over the amnion, and at what proves to be the posterior end of the embryo, serves to attach the blastoderm to the trophoblast (Figs. 280, D; 281, D; 282). This mesodermal attachment later comes to constitute the umbilical stalk already referred to, and into it there presently grows a small outpushing from one side of the sac where the latter joins the blastoderm. It is the beginning of the very small allantois (Figs. 279, 280, D, E). 550 EARLY MAMMALIAN DEVELOPMENT

Although at first located somewhat dorsally, the embryonic end of the stalk soon moves around so as to be attached to the embryo on its ventral side. It retains, however, its original point of attachment to the chorion since it is here that the placenta is to be formed.” From this description it is evident that in the Primates, the allantois, or more strictly in this case, the umbilical cord, does not grow out from the embryo to the trophoblast. It is there from the first.”

As concerns the yolk-sac, it is only necessary to state that it is very rudimentary, having little or no function. The space which might otherwise be occupied by these appendages, however, is eventually filled in this order by a very large amnion.“

Implantation and Placenta Formations-—According to previous accounts ovulation occurs following what amounts to a pro-oestral uterine hypertrophy, and the blastocyst reaches the uterus while the latter is under the influence of the progesterone of the succeeding corpus luteum. Here implantation takes place through the erosion of the hypertrophied endometrium by the newly arrived blastocyst between one or ‘two weeks following ovulation. This is of course previous to the time of the menstruation which would have occurred had pregnancy not intervened.

As in the case of the Rodents the details of the implantation process vary somewhat. In this instance, the chief variation occurs. so far as is known, between two groups, i.e., Tarsius, together with the other lower Monkeys, and the higher Apes, together with Man.

As regards the first group, i.e., that of Tarsius and the Monkeys, the description may be brief. The region of implantation may occur on the dorsal or ventral wall of the uterus, depending upon the form in question, and is not marked by either pits or folds, as in the Rodents. When

" In Tarsius the placenta is’ formed on the opposite side of the blastocyst, and the stalk shifts its point of attachment to the trophoblast accordingly. V

‘3 In a more recent human specimen. the Martin-Falkiner blastocyst C38), estimated at seventeen days of age, a somewhat different theory is expressed concerning the development of these structures. These investigators seem to think that both the yolk-sac and allantois may arise as vesicles developing in the inner cell mass itself, and that they may later all run together. If this is true it involves a somewhat novel method of gastrulation, and a peculiar fate for the allantois. Since there is some question about the normality of this embryo, theories based on it should await confirmation from the study of more specimens.

“ Though not (iertainly known, it appears that the amnion in the Primates (excepting the Lemurs, in this instance including Tarsius) is formed in a manner similar to that described under method II, i.e., by the development of a cavity in the embryonic knob!" The process in this group differs from that described under types I) or c of the second method, however, in that in this case the embryonic knob does not move down to the opposite side of the blastocyst. THE PLACENTALIA 551

the trophoblast of the blastocyst comes into contact with the hypertrophied uterine endometrium it promptly erodes the epithelium. A discoidal placenta which is very similar, if not identical, with that described for the Rodent, then develops at the place in question. Later, a

Fig. 283. —— Development of the fetal membranes in Tarsius. From Jenkinson (Vertebrate Embryology). After I-lubrecht.

a. Blastocyst before Rauber’s cells have disappeared. I). The embryonic knob (e.k.) is being folded out to the surface; the yolk-sac is complete. c. The embryonic plate (c.p.) is at the surface, the extra-embryonic coelom (c) is formed. (1. The

tail fold of the amnion is growing forward (t.am.), the allantois (all.) has pcnc-'

trated the mesoderm of the bodystalk, a placental thickening has been developed at the anti-embryonic pole. e. The amnion is closed and the body-stalk or umbilical cord (u.c.) is shifting its position, to be attached to the placenta (pl.).

second similarly shaped placenta may form where the blastocyst comes in contact with the opposite side of the uterus. The umbilical cord, of course, reaches only one of these, but the two are connected by blood vessels (Fig. 283, only one placenta in this case). ‘

Considering now the second group, i.e., the higher Apes and Man, it unfortunately happens that as regards the earliest ‘stages relatively little is definitely known, chiefly because of the scarcity of material. Some of 552 EARLY MAMMALIAN DEVELOPMENT

the earlier classic cases which have been studied comprise the Miller blastocyst Streeter (’26) with an estimated age of ll days and a diameter of 0.4 mm., the Bryce-Teacher blastocyst, estimated age 12—14 days, diameter 0.64 mm., and the Peters blastocyst, estimated age 14-15 days. diameter 1.1 min.” Somewhat more recently others have been added to

m. b.v. _ d. b. tr.


d. r. ep.

Fig. 284.——Early Human embryo with its membranes. From Jenkinson (Vertebrate Embryology). After Peters. "

am.c. Amniotic cavity. c. Extra-embryonic coelom. d.b. Decidua basalis (serotina). d.r.ep. Uterine epithelium covering the decidua reflexa or capsularis. l. Lacuna in trophoblast (tn). gl. Uterine gland. m.b.v. Maternal blood-vessels opening here and there into lacunae. cl. Clot marking (probably) the point of entrance of theblastocyst; here the uterine epithelium is interrupted. y.s. Yolk-sac.

the list, all of about the same or slightly greater estimated age. Thus there is the Werner (Stieve) blastoeyst at 12 days, and the EdwardJones-Brewer blastocyst (Brewer, ’37) at 15 days with internal dimensions of 1.85 x 1.71 x . 1.01 mm., and the previously mentioned Martin-Falkner hlastocyst, estimated age 17 days with possible abnormalities. Latest of all, are the Hertig-Rock blastocysts, one of which (not shown in the figures) is estimated at about 7 days, the youngest yet dis 15 Whether some of these specimens have quite reached the blastocyst stage is

perhaps open to question: but they are certainly not “ ova ” as they have sometimes been designated. ' ' v »


__ .... _,.,, A,.,._ THE PLACENTALIA 553

covered (Hertig and Rock, ’4l; Figs. 281, 282). The additional data from all the clearly normal sources, however, has not substantially modified the conclusions previously held concerning the early stages already described, and the processes about to be discussed. From information obtained from these early specimens, and from conditions which are known to exist later on, implantation and development both in Man and the higher Apes is thought to be as follows:

The blastocyst usually becomes attached to the dorsal (i.e., posterior) wall of the uterus in Man, and to the ventral (i.e., anterior) wall in the Apes; here the trophoblast promptly starts its work of erosion. In this case, however, the process goes much further than in the instances so far noted. In fact, it is thought that by this means the blastocyst becomes completely buried in the mucous layer of the uterus, while the epithelium closes behind it. It thus virtually occupies the position of an internal parasite within the uterine tissue (Fig. 284). As growth now proceeds, the blastocyst, covered by a layer of uterine mucosa and some epithelium, begins to project into the cavity of the uterus. Meanwhile, it appears that changes are taking place in the trophoblast, or chorion, as it may be called, quite similar to those which occurred in the Rodent, i.e., a thickening, and the formation of lacunae. In this case, these processes by which the trophoblast is thus converted into the trophoderm at first occur on every side of the blastocyst. Presently, however, the trophodermal development becomes much more marked on the inner side, i.e., that side away from the cavity of the uterus, and it is here that the permanent discoidal placenta is soon formed.

Throughout the trophoblast or chorion (now trophoderm) but especially on the placental side, the embryonic blood vessels, surrounded by a sheet of connective tissue (chorionic mesoderm), are working their way among the lacunae, into some of which they project. These vessels and their connective tissue are covered with a’ thin trophodermal cell layer known in human embryology as the cell layer of Langhans. Outside of this, there is an added layer of the trophoderm which is syncytial, and is apparently derived from the cells of Langhans, the latter being gradually used up. Thus, where the blood vessels, pushing their trophodermal and mesodermal layers before them, project into the lacunae, they have something like the appearance of villi, and are often so referred to (Fig. 285). It should be clearly understodd, however, that these “ villi” are in no sense homologous with the true villi described in connection with the indeciduate placenta of the Ungulates. They are not indeed essentially different from the capillaries‘ which push into, 554 EARLY MAMMALIAN DEVELOPMENT

Fig. 235.~— Diagrams illustrating the development of the “villi” in the Human placenta. From Kellicott (Chonlate Development). A, B. After Peters. C. After Bryce. A. Chorionic mesodetm just beginning to extend into the villi. B. Mesoderm invading the villi which are now branched. Layer oi Langhans cells forming beneath the syncytintrophoderm. C. Continued branching of the villi, all now covered only by the syncytiotrophoderm and the single layer of Langhans cells.

_ b. Decidua basalfs. cb. Capillaries of the decidua basalis. cv. Capillaries of the villi. e. Endothelium of the maternal capillaries. f. Fibrin deposited at the junction of the trophoderm and decidua basalis. i. lntervillous cavity (i.e., lacuna or sinus) filled with maternal blood. L. Langhans ‘cells. In. Chorionic mesoderm. s.

Syncytiotrophoderm. t. Trophoderm. 1:. Villi. vf. Fixation villi, i.e., those which extend clear across a sinus. THE PLACENTALIA 555

Fig. 286. —A. A diagram of an idealized section through the inner portion of the wall of the non-pregnant uterus a short time previous to the beginning of menstruation. The muscular layer is very thick, and only a small portion of it is shown. Beyond this layer on the outside of the uterus would come the peritoneal covering or serous membrane which here as elsewhere is quite thin. B. A diagram of a similar section through the Human placenta at a slightly later stage than that shown in Fig. 2§S {according to Jenkinson). The trophoderm, it will mired, has pen. etrated slightly into the compacta in this stage, so that the_ villi are more firmly attached. Note that these “ villi ” are quite different in their relation to the niaternal tissue from that observed in the Ungulates, (Compare Fig. 271). No attempt has been made to distinguish between affereiit and efierent hlood vessels, although itdis to be understood that both types exist on both the embryonic and maternal si es.

.bc. Blood capillaries in the mucosa. c.l.L. Cell layer of Langlians, still clearly in evidence. Chr. Chorion consisting of trophoderm plus extra-embryonic imz.-tvoderm. co. Compacta. d. Decidua; for explanation of terms see further in text. f.bz-. Fetal blood vessels. m. Muscular layer of uterus, or muscularis, ,only a small portion of which is shown. mbv. Maternal blood vessels. n.ugl. Necks of uterine glands in the compacts. s. Sinus lined by syncytial trophoderm, and filled with maternal blood. That the syncytial layer and cells of Langhans line the sinuses on the side of the decidua is questioned by some authors. sp. Spongiosa. str. Syncytial trophoaerm. tunes. Tgophodelrrlrlial ”(chorionic) rnesoderm. u.ep. Uterine epithelium. u.gl. Uterine g an s. v. i us.

1 556 EARLY MAMMALIAN DEVELOPMENT

and are hence covered by, the trophodermal material in the Mouse or Rabbit. As regards the lacunae, they are again filled with maternal blood, and are often termed “ sinuses.” They also are lined by a syncytial layer of the trophoderm augmented to some extent by a layer of the cells of Langhans, similar to, and continuous with, that which covers the connective tissue of the fetal capillaries (J enkinson) . Outside of the discoidal placental region, the whole blastocyst is growing out so as to fill the"cavity of the uterus (Figs. 287 and 288) . Its wall in this area consists internally of extra-embryonic mesoderm, and externally of the trophoderm, the two together as usual constituting‘ the chorion, while within this chorionic trophoderm the “ villi ” and lacunae are only slightly developed. Lastly, tightly adherent to, and covering this trophoderm, comes the uterine mucosa and epithelium which covered the blastocyst after its embedding in the

Fig. 287.——-Human embryo of the fourth uterine wall‘ A5 growth con’

month in ulero, showing the arrangement of tinugs, this epithelium is even. the membranes and placenta. From Kellicott

(Chonlate Development). After Strahl. many bound to come in con‘ c. Chorion and amnion. p. Placenta. LL. tact with that which lines the

Umbilical Cord‘ walls of the uterus at other points. By the time this occurs; however, the uterine epithelium and mucosa covering the growing blastocyst has become distended and is disappearing. Thus the trophoderm of this region is brought into direct relations with the epithelium which elsewhere still remains on the walls of the uterus, and this epithelium too presently disappears. Concurrent with the complete filing of the uterus and the disappearance of all its

epithelium the chorionic layer of the blastocyst is everywhere united to .

the sul)-epithelial mucosa of the uterine wall. It is only in the region THE PLACENTALIA 557


I.-u.

d. v.

Fig. 288.—Diagrammatic section through the pregnant human uterus and embryo at the seventh or eighth week. From Jenltinson (Vertebrate Embryology). After Balfour, after Longet.

am. Amnion. a.m.c. Amniotic cavity. The latter has enlarged until it occupies nearly all of the extra-embryonic coelom (c), the amnion being reflected over the umbilical cord (u..c.) and yolk-sac (y.s.). The yolk-sac, it will be noted, is very small. d.b. Decidua basalis (serotinal, in connection with which the trophoderm or chorion, represented everywhere by fine stippling, gives rise to the placenta. Thus the chorion in this region is the chorion frondosum. d.r. Decidua capsularis (refiexa), consisting of a thin layer of. uterine epithelium and mucosa. It soon disappears, exposing the vacuolated trophoderm (chorion) beneath, which in this region becomes the chorion laeve. d.v. Decidua vera, whose epithelium also disappears when the trophoderm beneath the capsularis (chorion laeve) comes in contact with it. Lu. Lumen of uterus, presently obliterated. o.d. Oviduct whose direction in the non-pregnant uterus would be nearly horizontal. pl. Placenta; for details see Fig.

of the placenta, however, that the chorion normally continues to be vascularized and to thicken by the growth of villi.

The placenta, as so far described, consists then essentially of a greatly thickened layer of trophoderm containing lacunae or sinuses filled with maternal blood, while into and across these sinuses extend chorionic processes or “ villi” containing fetal connective tissue and capillaries. The layer thus indicated is obviously essentially tissue of embryonic origin, and is sometimes known as the “ placenta proper.” Between it and the muscular wall of the uterus there still exists a certain amount of 558

EARLY MAMMALIAN ‘DEVELOPMENT

the uterine mucosa, i.e., that part of the mucosa which the trophoderm has not destroyed. It now remains to state that in some of the higher Apes and Man (as well as in certain of the lower animals already discussed, e.g., the Cat) this portion of the ‘mucosa is itself differentiated


Fig. 289. —— Reconstruction of a human embryo of 2.6 mm. From Minot (Laboratory Text-Book of Embryology). After His.

/1. Aortic limb of heart. All. Bodystalk. A0. Dorsal aorta. Au. Umbilical arteries. Car. Posterior cardinal

vein. Jg. Anterior cardinal vein (internal jugular). Om. 0mphalomesenteric vein. op. Optic vesicle. or. Otocyst. V It. Right umbilical vein.

This completes the description

into two main layers. The outermost of these layers adjacent to the muscularis is filled with glands, and is known as the spongiosa. The second layer, to which the trophoderm is firmly adherent, and in which it is in fact slightly embedded, is occupied by the straighter smaller portions of these glands, i.e., their necks, and is called the compacta (Fig. 286). Moreover, the compacta and spongiosa not only exist in the region of the placenta, but likewise at all other points around the uterine wall.“ Thus, when the non-placental trophoderm of the enlarging blastocyst eventually comes into contact with this wall from which the epithelium soon disappears as indicated in the preceding paragraph, it becomes here also adherent to the compacta. During the later stages of pregnancy, both the compacta and spongiosa tend to degenerate and to become stretched and thin. It is then through the region of either one or both of

these layers that the tissue breaks at the time of parturition. of the placenta and the adjacent re gions in Man and the Apes. It remains, however, to indicate the names by which the various parts are known in human embryology. To understand the significance of this nomenclature, the student must bear in mind the older idea that placentas of this type were truly deciduate.

16 The spongiosa and compacts indeed occur not only in the pregnant Primate uterus, but in the non-pregnant uterus as well, particularly just previous to men struation. THE PLACENTALIA V p . 559

That is, it was thought that a large part of the uterine wall was deciduous, i.e., torn away or shed at parturition. Hence those layers of the wall (i.e., the mucosa) which were supposed so to behave were termed the decidua. Also in correlation with this idea, most of the placenta and the covering of the blastocyst was supposed to be formed out of this decidua, rather than out of trophoderm. With this in mind, the reasons for the following names are fairly evident:

That part of the uterine wall to which the placenta is attached is known as the decidua serotina, or decidua basalis (Fig. 288). The portion of uterine mucosa and epithelium which, during the earlier development, covers the blastocyst on the side opposite the placenta, is called the decidua reflexa or decidua capsularis. That is, this portion is, as it were, reflected

Fig. 290.—Human embryo of about 23 days (4.0 mm.). From Minot (Laboratory Text over the blastocyst, forming 300/t of Embfyolvgfb After His ‘Emb1‘:v'0 0) . dl. Fore-limb bud. BS. Body-stalk. Op. Op31 cover or capsule for It‘ tic vesicle. pl. Hind-limb bud. IV. Fourth ven L t1 the 1-emainin art of tricle of brain. 1. Mandibular process. 2. Hythaes uiérine wan witghpwhich oid arch. 3, 4. Third and fourth visceral

arches.

the thin chorion, now lack ing the overlying decidua reflexa, finally comes in contact, is known as the decidua vera, and as this contact occurs the decidua Vera disappears down to the compacta. Not only are the parts of the uterus thus named, but the parts of the chorion are also defined. That part which forms the placenta and adheres to the decidua serotina is termed the chorion frondosum. The remainder, at least after its loss of the first slightly developed “ villi,” is the chorion laeve.

Comparing the means of embryonic nourishment in the Primates with those in the Rodents, there appears at least one notable difference. In the Rodents the yolk-sac probably plays at least some part in obtaining nutriment for the embryo throughout development; in“the Primates (except the Lemurs), on the other hand, this function, as well as that of respiration, is entirely subser-ved by the placenta. Coming to the actual structure of this organ itself, there exists a striking similarity between 560 EARLY MAMMALIAN DEVELOPMENT

the two orders. There is also, however, a slight difference here, which is perhaps worth noting. At the time of parturition in the Rodents scarcely any maternal tissue, save blood, is lost, and hence the placenta is not at all deciduate in the strict sense of the word. In the Primates, on the other hand, there is a certain amount of the compacta and perhaps of the spongiosa lost at birth, and this is maternal tissue. Hence the Primate placenta, at least to this slight extent, may be said to be truly deciduate. The body—stalk in the two groups is in general similar in lack ing any extensive endothelial element. As has been noted, however, its method of formation is different. 15

EVELOPMENT OF THE PIG TO THE TEN MILLIMETER STAGE

I N the preceding comparative discussion of the early stages of various representative groups of Mammals we have carried the history of the Pig in particular to about the thirteenth day of its development. This means of course thirteen days from the time of fertilization in the upper part of the oviduct. During this time, as we have seen, the egg has reached the uterus, developed into an elongated blastocyst, and the blastocyst is becoming implanted. The embryo itself is represented by a blastoderm in which a primitive groove and notochord are evident, and in which the three primary germ layers have already been diHerentiated as previously described. The nature of the archenteron, and its re lation to the blastocoel has also been indicated.

Having reached this point, we are now prepared to proceed with a description of the further development of this animal. In doing so we are once more faced with the problem of whether to describe the complete development of one system at a time, or to carry all systems along together as it were, in a series of stages. For fairly obvious reasons it is not practical in the case of the Mammal to proceed very far by daily periods. Furthermore, through study of the Frog and Chick we are now familiar enough with the vertebrate plan of development so that we are aware in a general way of what other systems are doing while we concentrate our attention upon one. For these reasons a sort of compromise between the system plan and the stage plan becomes possible. Beginning at the present point therefore we shall carry each system of the Pig to completion in two main steps. The first step will take us to the condition which exists at the 10 mm. stage (20-21 days), a condition more or less comparable with that of a 4-5 day Chick. The second step will then bring the system in question to completion, or as near to it as it is necessary to go. As we proceed with these steps, however, it is desirable from time to time to mention the number of somites present, and also the approximate length of the embryo. In the latter connection certain facts concerning the general form of the animal need to be mentioned, 562 THE PIG TO TEN MILLIMETERS

and we shall take those up at this point, together with a few comments on other external features.

Embryonic Flexions and Rotation. — As in other Vertebrates, so in the Pig, the very early stages pose no question as to what line constitutes the longitudinal embryonic axis. This is obviously indicated by the line of the primitive groove and notochord, and presently also by the line of the fused neural folds, and the contours defined by the folding oil of the embryo. This simple condition persists up to about the ten somite stage, when the embryo is approximately fifteen days old and measures from 3 to 4.5 mm. in length (Fig. 291). Shortly after this, how="¢U"3' §"°°V° ever, as in the Bird, vari



T‘ eural fold

Cgtedgfi “ ous curvatures begin to o ammon .

- r , , develop, and certain flex smus rhomboldahs . _ d pmnmve streak: ures are again recognize .

The cranial and cervical flexures are the same as

in the Chick, and in addi Fig. 291. — Surfacfi View of a Pigf ernbrylp fofd7 {ion two others are named somites (3 mm.), 5 owing c osing o neura 0 s. . . . Amnion removed. After Keibel. whlch mlght 3150 be de5‘g'

nated in the Bird, but usually are not. These are the dorsal and lumbo-sacral flexures which refer

simply to the successively more posterior parts of the continuous curvature. The caudal flexure mentioned in the account of the Chick also exists in the Mammal as a continuation of the lumbo-sacral flexure, but is not generally especially designated (Fig. 294-). It should also be noted thatlfor a brief interval before the caudal and lumbo-sacral flexures develop there is, as was also true of the Chick, a slight ventral bend in the m_id—body region due again apparently to the pull of the yolkstalk (Fig. 292). This, however, is quite transitory. As soon as these curvatures develop the question at once arises as to which of the infinite number of straight lines which might be drawn through the embryo is to be designated as its length. In Mammalian embryos, including Man, there are two such lines which are quite commonly used. One is a line passing from the most anterior point of the cranial flexure (mid-brain) posteriorly through the “ rump.” The latter may be defined as a point at about the middle of the convexity of the lumbo-sacral flexure, i.e.,

3 EXTERNAL FEATURES 563

somewhat posterior to a point dorsal to the origin of the hind-limbs. This line of measurement is the crown rump axis. The other is a line. from the posterior side of the cervical flexure, i.e., just over the ear, anteriorly, and again terminating at the rump posteriorly. Because of the position of the anterior point above the ear this may be called the

auricular rum p axis. All measurements referred to in this account will be those of the straight embryo previous to the development of its flexures, and later those of approximately the crown rump axis.

In this general connection one further matter pertaining to the curvatures of cut edge Mammalian embryos may ‘a’:‘3':h";‘:i';n;. be mentioned, though it i» has no reference to the E problem of measurement. It will be recalled that when the Chick developed its various flexures it also _ 1 acquired a lateral rotation . under chorion or torsion. In that case this i " ‘ rotation prevented the

burying of the anterior end Fig. 292. -— Surface view of a Pig embryo with

. about 16 somites (4.5 mm.), showing outpush“1 the yolk‘ In the Mam‘ ing of allantois beneath chorion. After Keibel.

cut edge of yolk sac


mal of course there is no

yolk, but it is an interesting fact that the lateral torsion still takes place to some degree (Figs. 292, 293). It is quite variable, as all vestigial structures and activities are apt to be, and soon vanishes entirely.

Other External Features.—Finally before proceeding to a dis-.

cussion of the specific systems a few further remarks are pertinent with regard to general external features, aside from the various curvatures. As will be apparent from Figure 294, four visceral arches and four “ clefts ” are in evidence, while about the two posterior clefts is a general depression termed the cervical sinus. As sections‘ reveal, however, these are not true cleft's since they do not normally actually open through into the corresponding visceral pouches, but- it is convenient to

refer to them as such. Also from the figure itmight at first be supposed" 564 THE PIC TO TEN MILLIMETERS

that there are five-clefts and five arches rather than four. The apparent first cleft, however, is really the space between the maxillary process and mandibular arch, and is therefore not counted as a cleft, nor is the maxillary process an arch. Immediately anterior to the maxillary process is still another depression separating this process from the front parts of the face (see below). This depression is the lachrymal groove. At its dorsal end is the eye, and at its ventral end the nasal pit. In this connection it may be appropriately noted that one of the few rather striking difierences between the appearance of the head of a 4-5 day

Chick and that of a 10


hyomndibuhr def‘. ':- mm. Pig is the much auditory Pit Jolt ,3; greater size of the eye in 2nd optic vgfldg the Bird. "l“°"l‘l°f“ 3rd 0" i Viewing the embryo somites' llnmd‘ from the front it will fur. amnion;

ther be seen (Fig. 295i _‘ that antero-ventral_t.o,the

eyes, between them and ‘ the olfactory pits, lie the naso-lateral processes, which as in the Bird bound the pits laterally. Medially the pits in the Pig are bounded by the naso-medial processes, structures not indicated in the Bird. A comparison of these forms, however, reveals that these last named processes are really only special differentiations (prominences) of the lateral parts of the naso-frontal process, which in the Chick is shown bounding the pits on their medial sides. In the Pig the region between the naso-medial processes, i.e., the middle of the “ naso-frontal process ” is sometimes termed simply the frontal process. However, this region is soon (10 mm.) merged with the naso-medial processes which may then be said to join each other in the mid-line. The oral cavity of the Pig soon appears therefore as an opening immediately beneath the fused naso-medial processes. This cavity as usual is bounded ventrally by the mandibular arches, while the maxillary processes are pushing into it from either. side. The latter are separated from the naso-lateral processes by-the lacrymal groove. Finally, among external features of the 10 mm. Pig, are the prominent paddle-like fore and hind limb buds and the numerous well-marked

somites. Both of course are highly reminiscent of the appearance of these structures in the Chick in a corresponding stage.


Fig. 293.-—Surface view of a 3.5 mm. Fig embryo

with chorion removed to show allantois. After Keibel. NERVOUS SYSTEM: EARLY DIFFERENTIATION 565

THE NERVOUS SYSTEM

As in the case of the Chick, much of the general form of the early mammalian embryo, as well as various prominences appearing upon it, are determined by the developing nervous system. It is therefore convenient to consider this system first.

Illrd viscera! arch

h 'd Nth visceral arch yo. arch



'mandibu|ar arch cervical sinus

forblimb bud - maxillary process‘


33% 5. :2 6””

7 mm. erribryo

Fig. 294.—Lateml View ‘of a 7 mm. Pig embryo with amnion and chorion removed.

EARLY DIFFERENTIATION

The System as a Who1e.—The nervous system first appears in embryos of about 2 mm. as the usual groove in an ectodermal medullary plate immediately anterior to the primitive streak (Fig. 264). Slightly later definite folds arise upon either side of this groove in essentially the same way as in the Bird (Fig. 291). The location where the folds most closely approach each other represents the future hindbrain region, while the wide open part immediately anterior to this is the future fore-brain. The neural tube proper is obviously not yet repre566 THE PIG TO TEN MILLIMETERS

sented, which means that the anterior parts of the system are as usual the first to form, and as in other cases maintain their advantage in precocity till very late in development. It will be noted that the chief difference between the situation in the Chick and the Pig at this stage is the wider flare of the folds in the anterior region of the latter. Slightly later,


frontal PTOCCSS olfactory plt

naso-lateral process _ '

- naso~medlaI process maxillary process

mandibular arch

hyomandibular clef: hyoid arch

lllrd viscera! arch 1

from 7 mm. embryo

Fig. 295.——Antero-ventral view of the head of a 7 mm. Pig embryo showing parts constituting jaws and face.

at about 10 somites, another difference becomes evident in that, as previously stated, the optic vesicles of the Pig are much less prominent than were those of the Chick at a comparable stage, and this remains true throughout the earlier periods of development. As will be apparent from

the figures, these vesicles, at their earlier stages, are also somewhat differently shaped from those of the Bird.

DIFFERENTIATION TO TEN MILLIMETERS

The Brain. —— Following this early condition the cranial flexure makes its appearance (13 somites), and shortly thereafter the cervical and caudal flexuresiare also under way. Thus by the 25 somite stage the anterior extremity is almost touching the heart in about the manner of NERVOUS SYSTEM: TO TEN MILLIMETERS 567

a 48-hour Chick with the mid-brain at approximately the most anterior point of the embryo. By this time also the various divisions of the brain are evident, and are the same as those in the Bird, i.e., the prosence phalon, mesencephalon and rhombencephalon. As will presently be noted these main parts are soon further subdivided, and give rise to the same structures as enumerated in the previous form. Thus at 10 mm. (Figs. 296, 297) about the same degree of development of the brain exists, with the same parts in evidence as in a 4-5 day Chick. The proscncephalon is divided into telencephalon and diencephalon, and the former is giving rise to outgrowths (telencephalic vesicles) which will become the cerebral hemispheres. The diencephalon, which is separated from the telencephalon by the same features as characterized the Bird, has, as before, given rise to the optic vesicles and the infundibulum. The chief difference between this part of the Pig brain at this time, and that of the 4-5 day Chick, is the lack of an epiphysis in the Pig, in which it does not appear until considerably later. The mesencephalon is as usual 3. very prominent region whose protruding anterior side marks the apex of the cranial flexure. It is, however, not so well developed as that of the Chick at a corresponding stage. This is correlated with the fact that this region is the site of the future optic lobes of the Bird, which are more prominently developed than the partially comparable ‘corpora quadrigemina of the Mammal. A sharp fold, the isthmus, separates the mesencephalon from the following rhombencephalon, and the division of ‘the latter into metencephalon and myelencephalon is now distinguishable by the thickened sloping roof which characterizes the former (Fig. 297).

The Neural Tube and Crests. —- Passing posteriorly we find that, as in the Frog and Chick, the neural tube has been formed by the closing neural folds so that its dorsal and ventral walls are thin and its lateral walls relatively thick. By the 10 mm. stage the cells in these walls are becoming differentiated into several different types, some of which have already been mentioned in the case of the Chick. Near the delicate internal limiting membrane lining the neural canal the original germinal cells have given rise to spongioblasts and the latter to supporting cells with long fibers running toward the outer periphery of the cord. Again as in the Bird these supporting elements are called ependymal cells. The larger part of the cord, however, is occupied at 10 mm. by the mantle layer, consisting of other germinal cells in process of further division and differentiation as follows: Some of the germinal cells become spongioblasts which in this layer eventually form other types of supporting cells known as short and long-rayed astrocytes. The remain568 THE PIG TO TEN MILLIMETERS

tier of the germinal cells in the mantle layer are neuroblasts which later differentiate into actual nerve cells. Finally outside the ependymal and mantle layers, beneath a thin outer" limiting membrane, there occurs a non-nucleated region termed the marginal layer. Because of the lack of

myelencephalon Vlllth and Vllzh (genleulate) ganglia





lX“(‘ 8‘"8l:)°" audkor), “Sid, metencephalon Xth gangllon jugula . '¢ Vth(Gasserian) ganglion

' A lVth nerve Xlth spina'laccess_ory nerve '5ml°'::;";‘°:;:l°" Fig.1” Frorlep sgangluo . F3’. 2” xnth-he.-.,¢.,-00;; - ophthalmic nerve petrosal ganglion

. maxillar nerve ganglion nodosum Y ‘ 'diencephalon


Fig. 302 ' F?s- 302 xth nu,” / Rathke's pocket esophagus ‘ Seesell‘s pocket ' OptIC cup Fis_ 3°“ ‘ ' Fig. 301 _mng telencephalon F‘ 305 W c:narndIib‘ular n rveF;'_ 305 ---?{7;--— ° 3 0 Y P yuzel Inelyolldstalk 533.306 Fin» 306 t ch " - _

a:t":..a 3» 3;; d°rsa s allantoie stalk , Fig. 3l0 FIg.3l0 l ncreas . ventrzamabladder postncloacal gut. Fig. an “9~ 3"

a,.:m “-9- 313 l spinal ganglion C mm

mesonephros

nephrogenous tissue of metancphr mcsonephricvduct

Fig. 296.——Reconstruction of a 10 mm. Pig embryo, designed to show primarily the main features of the nervous, digestive, respiratory and excretory systems at this stage. Drawing made chiefly from a study of sections, with aid from a wax reconstruction produced under the author’s direction in the Oberlin College Zoological Laboratory. Lines at the sides with figure numbers over them indicate where the sections represented in these figures pass through the embryo. By laying a ruler along any pair of lines the structures cut by the respective section may be seen. *

nuclei, it stains very lightly compared to the darker more central regions. It will further be noted in sections of the 10 mm. Pig that portions of the mantle layer extend ventro—laterally somewhat, causing the lower sides of the cord to bulge slightly. These extensions are the beginnings of the ventral horns (Fig. 298).

Aside from the cord itself it will be found, as in the case of the Frog NERVOUS SYSTEM: TO TEN MILLIMETERS 569

and Chick, that as the neural folds come together a hand of cells is pinched off between the tube and the overlying ectoderm. The cells of this band soon become concentrated on either side to form the continuops neural crests. The latter are then further concentrated segmentally

pharynx metencephalon




notochord

mesencephalon

Ra:h$<e's pocket v Seesell’s pocket

./ optic chiasma , Optic recess

lamina terminalis

um bi Iical artery

vltelline vein

posterio vena cava


mesoneph ros

dorsal root ganglion

Fig. 297.-—Mid-sagittal section of a 10 mm. Fig embryo.

to form the groups of neuroblasts which develop into the spinal ganglia. By the 10 mm. stage each such ganglion is clearly defined, and has given rise to the dorsal roots of the spinal nerves which are definitely connected with the cord. y The Cranial Nerves. —— In the 10 mm. Pig all the cranial ganglia -and nerves are represented except the I or oljactorf, and the II or optic, the optic stalk not yet containing any actual nerve fibers (Fig. 296). 570 THE PIG TO TEN MILLIMETERS

The III or oculomotor nerves can be plainly seen emerging from the ventral side_ of the mesencephalon, while the IV or trochelar nerves are just starting from the dorsal side of the fissure (isthmus) between midand hind-brain. The V or trigeminal nerve ganglion of each side appears on the ventro-lateral side of the myelencephalon near its anterior end. It is united to the brain by a large root, and from it emerges anteriorly the ophthalmic nerve, while more posteriorly and ventrally arise



external llmltlng membrane

lumen of neural tube

mantle layer prlmordlum of

ventral horn blood vessel

K

I .- 1.1‘

»‘3 ventralnerve root ~:


internal Ilmltlng Vf membrane


Fig. 298.———-Transverse section of the center and right side of the nerve cord and a spinal ganglion of a 10 mm. Pig embryo.

-the maxillary and mandibular nerves. The entire complex lacks the distinct V shape which it had in the Chick due to the large mass of the ganglion proper which obscures the base of the V. More ventral than the V nerve ganglion, at about the middle of the myelencephalon the VI or abducens nerve of either side takes its origin, while above it at about the level of the V ganglion occur the ganglia of the VII and VIII nerves. These latter ganglia are somewhat dorso-ventrally elongated structures much less massive than the V. The VII or geniculate ganglion is very close to the VIII pr acoustic, but is slightly anterior to it, and the branches of the VII or facial nerve are little developed at this time. The acoustic or auditory ganglion in turn is in contact with the auditory vesicle which lies posterior to it, the short branches of the auditory nerve not being in evidence as yet. There is no single glossopharyngeal NERVOUS SYSTEM: TO TEN MILLIMETERS 571

ganglion in the Pig. Instead the erve cells which would constitute this ganglion are divided into two groups, a dorsal and a ventral. The dorsal group is in close contact with the posterior side of the auditory vesicle, and is called the superior ganglion of the IX or glosso pharyngeal nerve. The ventral group occurs both ventral and slightly posterior to the superior ganglion, and is known as the petrosal ganglion of the same nerve. As in the Chick, the X or vagus ganglion occurring just behind the IX is also divided into two parts, the ganglion jugulare and the ganglion

lXth Xth


}cranlal nerve ganglion

hind-brain (metencephalon) 1.3-‘

branches of anterior cardinal velni

mid—brain (mesencephalon)

Xlth cranial nerve (spinal accessory)

cndolymphatic duct

Fig. 299.—Transverse section through the brain region, including some of the spinal ganglia, of a 10 mm. Fig embryo. See reconstruction Fig. 296.

nodosum. The former is so closely in contact with the superior ganglion of the IX at this time as to be scarcely distinguishable as a separate ganglion (Fig. 299). From it there arise two thick strands of nerve fibers. The more dorsal of these proceeds posteriorly to meet the XI nerve, along whose posterior part it extends for a way, as the elongated commissural or accessory ganglion. The second strand passes postero-ventrally, and shortly enlarges to form the ganglion nodosum indicated above. From the latter the vagus nerve containing both afferent and efferent fibers is evident at this stage proceeding toward the viscera. The fibers of the XI or spinal accessory nerve, already referred to, also pass antero-dorsally from the nodosum toward the ganglion jugulare along with those of the X nerve. Before reaching this ganglion, however, these fibers branch off in a well-defined strand which curves dorsad, and proceeds along the side of the myelencephalon until it ends in F r0riep’s ganglion. This latter ganglion later disappears, and the nerve is entirely motor. The XII or hypoglossal nerve is also entirely motor, and

J‘: 572 THE PIG TO TEN MILLIMETERS

hence has no ganglion. It arises as a g oup of fibers ventral to the spinal accessory, and these shortly unite to form a single trunk (Fig. 296).

The Spinal Nerves. — We have already noted the origin of the dorsal root ganglia and the fibers connecting them with the dorsal part of the spinalicord. These are of course sensory nerves. The ventral root motor nervefibers originate in the ventro-lateral portions of the mantle layer of the cord, whence they emerge opposite each dorsal root (Fig. 298). As in the Chick, they then very shortly join the sensory fibers running outward from the dorsal root ganglion, and from near the point of union three branches arise. The most dorsal branch of each spinal nerve is a dorsalsomatic ramus, and the middle one a ventral somatic ramus, both containing mixed sensory and motor fibers just as they did in the Bird. The third and most ventral branc-h, also as in the Bird, is a ramus conzmunicans of the sympathetic system, except in the sacral region whose communicating rami belong to a part of the parasynz pathetic system. The cell bodies which give rise to the fibers of all these rami lie, as in previous cases, within the nerve cord, and are known as preganglionic Izeufanes. On the other hand the neurones ( postganglionic) which constitute the chain ganglia of the sympathetic and parasympathetic systems to which the fibers of the rami run, have as usual migrated thence from the nerve cord, the dorsal root ganglia, or both. This is also of course true of the neurones in the various visceral plexuses. In the case of the Pig, however, it has not been possible to analyze the exact sources of these postganglionic and visceral neurones as carefully as in the Frog and Bird. This is because of obvious limitations on experimental procedure. Also there seems to be no data as to whether the permanent system is preceded by a temporary primary one as in the Chick-. Lastly, in connection with the parasympathetic system referred to above, it may be noted that the preganglionic neurones of this system not located in the sacral region, occur in the brain. The parasympathetic and sympathetic systems together are often referred to as the autonomic system.

One interesting point concerning the spinal nerves which is true of all the vertebrate embryos with appendages, comes out especially clearly inrthe 10 mm. Pig. This is the modification in the original strictly segmental arrangement of the spinal nerves. Though this arrangement is still marked, the fusing of several branches in their respective regions to form the brachial and sacral plexuses is very evident. Also the caudal migration of the appendages is indicated by the fact that the branches which form the respective plexuses arise from regions of the cord considerably anterior to the limbs which they supply. The caudal movement DIGESTIVE SY STEM: EARLY STAGES 573

of the diaphragm is likewise evidenced by the anterior origin and backward extension of the phrenic nerve it this stage. In later stages this nerve continues to follow the diaphragm as it moves posteriorly.

The Organs of Special Sense. — As inthe case of the parts of the nervous system just described, the organs of special sense in the 10 mm. Fig are also developed to about the same extent as those of a 4-5 day Chick. Thus the olfactory pits already noted in the account of the exterior, are present opposite the prosencephalon. Further back the optic vesicles have formed cups in the usual manner, and each cup is oc} cupied by a hollow sphere of cells destined to become the lens. As in] dicated above, these forerunners of the eye are definitely much smaller 1 relatively than they were in the Bird, but they have formed in the same

fashion from the same parts. Likewise the auditory vesicles have arisen on either side of the hind-brain by invagination from the surface ectoderm in a way already familiar. They are about the same shape as those of a 5-day Chick with the endolympliatic ducts extending dorsalward in the usual manner. As in previous cases these parts are in close proxim- . ity to the hyomanclihular pouch which will form the middle ear and Eustachian tube (Figs. 296, 299, 302).

THE DIGESTIVE SYSTEM ‘ EARLY STAGES

The Primitive Gut and Related Parts. —— We have already noted , that in the Pig. as in the Chick. the embryo forms from a fiat plate of

cells by a folding off process. Also by the time this occurs the germ lay‘ ers have arisen and the. mesoderm has been more or less completely split into the somatic and splanchnic sheets. Hence the innermost layers of the folds which form the gut will consist as usual of the splanchnic mesoderm and the endoderm (splanchnopleure) . As in the Bird, the folding ' off is accompanied by the outgrowth of the distal rim of the fold, especially anteriorly and posteriorly. Thus the fore-gut and hind-gut are lengthened (Fig. 300). As in the Bird the proximal rim of the fold, on the other hand, either remains stationary or actually draws together i somewhat. Insofar as this latter movement involves the splanchnopleure Q it produces a great relative narrowing of the yolk-stalk or yolk-sac um‘ bilicus (see Chick, Fig. 190), so that the gut cavity is more and more I 1

sharply separated from the remainder of the extra-embryonic portion of the archenteron. The folds of the somatopleure of course follow, thus narrowing also the somatic umbilicus, or as it is called in the Mammal, the body stalk, or later the umbilical cord. 574 THE PIG TO TEN MILLIMETERS

In connection with this process there are, however, certain differences to be noted between the Chick an l Pig. In the first place it appears that the folding off is somewhat more nearly simultaneous anteriorly, laterally and posteriorly in the Pig than it was in the Chick, though even in the former the head fold is a little precocious. A second difference is perhaps more striking, and has already been referred to. It is the fact that at a very early stage the mesoderm develops anteriorly as well as lat amniotic heiad told

,7

"method Mung PI“: amniotic tail fold ' anal plate



A °"3lPlfl€ periczrdtal coelorn Ik mflodflm yo 5“ endoderm chcfionk uaphabhn amniotic head fold neural tube amniotic nail fold amnion


eczoder chorionic trophohlasl ,,,,m°n notochord . Fla“ cmdum

\ mesoderm

mesoderm ‘_ ‘O \‘

hind-gut


yolk sac mesoderm yolk sac endod:rm/ perlardial coelom

B

Fig. 300. —-— Diagrammatic mid-sagittal sections through early Pig embryos to show primarily the method of origin of the allantois which is slightly difierent from that in the Chick. See Fig. 198. Note also the relatively equal growth of the head and tail amniotic folds as compared with their unequal growth in the Bird.

erally and posteriorly, so that there is no proamnion region which is free of it. Hence the mesoderm is involved in the head fold of the Pig from the first, the same as everywhere else. Still a third dilierence between Bird and Mammal has to do with the behavior of the mesoderm beneath the forming gut. In both organisms it will be noted that as the lateral folds of the splanchnopleure press toward each other the layers of endoderm are the first to meet. Wliereupon they fuse and at once close off to form the completed endodermal tube, save for the opening of the yolk-stalk. The splanchnic mesodermal layers of the splanchnopleure meet next and fuse, but do not close off. Instead they remain as a double sheet, the ventral mesentery, which unites the gutto the ventral body wall formed by the subsequent fusion of the somatic mesoderm and ectoderm. In both Bird and Mammal the dorsal part of this mesentery persists to help support the heart and liver. In the Bird, however, the most ventral part, i.e., the part which makes contact with the body wall, DIGESTIVE SYSTEM: EARLY STAGES 575

it may be recalled, almost immediately disappears. In the Mammal, on the other hand, this part persists much longer. Indeed in the latter, as

we shall see, some of it exists permanently, and we shall have occasion to return to it later on.

The Yolk—Sac. — While the folding of the splanchnopleure is forming the gut‘ and yolk-stalk, what remains ventrally of the original archenteric space becomes the yolk-sac. The endodermal lining of this sac

mcdullary plate


splanchnlc _ mesoderm ‘

somatic mesoderm

chorlonlc trophoblast

Fig. 301.——-Transverse section through a Pig blastocyst cutting the blastoderm and embryo at the level of the second somite. After Streeter, modified to complete the blastocyst ventrally. The embryo is the same as that reconstructed in Fig. 265. and measures 1.56 mm. in length.

has of coursebeen completed ventrally by the growth of this layer clear around the inside of the original blastocoel. The downgrowth of the mesoderm followed by its split into two layers, however, proceeds more slowly. Thus there is a time when this split mesoderm is pushing its way ventrad and medially from both sides, but has not yet met ventrally (Fig. 301). Shortly, however, it does meet, thus everywhere separating the endoderm of the yolk-sac from the trophoblast by a layer of extra-embryonic splanchnic mesoderm, the extra-embryonic coelom and a layer of extra-embryonic somatic mesoderm.

The Allantois. — As the above events are taking place (2—4.5 mm.) , it should be noted that at the posterior end of -the embryo a condition exists which at first seems very similar to that which prevailed in the Bird. Thus as in that case there is the same fold of the splanchnopleure which in the Bird we have called hind-gut, but which some have 576 THE BIG TO TEN MILLIMETERS

chosen to interpret as allantois. So far as the detailed events in this region have been described for the Pig, however, the subsequent differentiation of the actual allantois and the definitive hind-gut appear to dif~ fer somewhat from the history of these parts in the Chick. Thus in the latter the original fold constituting the primordial hind-gut (by some labeled allantois) is, according to our previously stated position, only partly allantoic. This was on the ground that it is not until after the tail-bud has swung around to the ventral side that a portion of this re lnrq visceral‘ arch Xth cranial nerve

end of 4th visceral pouch




mandibular arch

maxillary process

Pl‘3")’"* _/ i « _ -. , ' i ‘ portion of ' ' ' ' ‘ ' « cerebral hemisphert,

nerve I'O0C

dorsal spinal , nerve root ganglia ‘

cervical nerve


anterlor cardinal veln

3rd vlsceral clef: hyommdl I "I" dd‘

Fig. 302.—Transverse section through the eye and visceral arch region of a 10 mm. Pig. See reconstruction Figs. 296, 318, 320.

gion gives rise to an anterior outgrowth which is entirely allantoic. In the Pig, on the other hand, all of the original posterior fold continues its backward growth to form allantois. Shortly afterward another fold develops in the dorsal splanchnopleure slightly anterior to the allantoic

outpushing, and grows posteriorly above the latter to form the definitive hind-gut (Fig. 300). '

FURTHER DEVELOPMENT OF THE GUT

The Stomodaeum. — As in the Chick the fore-gut does not at first open to the outside. Soon, however, the ectoderm becomes invaginated to meet the endoderm at a point slightly posterior to the extreme end of the gut. This invaginated ectoderm is as usual the stomodaeum, and the double membrane formed by its fusion with the endoderm is the oral plate. Sometime between the 15 and 25 somite (4.5—-6.5 mm.) stage, this plate breaks through, and puts the stomodaeal cavity in communication with the future pharynx. The short portion of gut extending anterior to the stomodaeum isii temporary structure known as the pré-oral gut, or FURTHER DEVELOPMENT OF THE GUT 577

in the Mammal as Seesel’s pocket (Figs. 296, 297) .’ The stomodaeum itself later gives rise to the oral region involving the nasal, maxillary and mandibular processes. At 10 mm., however, the only structure which it has produced is an anterior outgrowth in the direction of the infundibulum of the brain. This diverticulum, as in the Chick, is Rathke’s pocket,

Fig. 303.——Reconstructions of the developing bronchi of a Pig’s lung at the stages indicated. After Flint. The arteries and veins, though only labeled in one figure, are represented in the same manner in each.

and is of course, the primordium of the anterior part of the pituitary. (See footnote on this topic in the section on the Frog.)

The Pharynx.——This region of the gut is rather shallow dorsaventrally, and at an early stage begins to show the lateral outpocketings which form the visceral pouches. There are usually four pairs of these in the Pig, the hyomandibular and three posterior to that pair, though

, the last (fourth) pair aresmall and sometimes entirely lacking (Fig.

302). In a 10 mm. specimen all the pairs destined to appear are well developed, and have come in contact with the corresponding ectodermal

“ clefts ” (Figs. 294, 296). As already indicated, in the case of the Pig, it is to be noted that, as in most other Mammals, these regions of con578 THE PIG TO TEN MILLIMETERS

Xth cranial nerve endocardi! cushion


ductus Cuvier valvulae venosae

Fig. 304.—~Transverse section through the heart and trachael region of a 10 mm. Pig. See reconstruction Figs. 296, 318, 320.

esophagus


mesonephros

“mg posterior vena cava subcardinal vein

Fig. 305. ——Transverse section through posterior of heart and the lung region of a 10 mm. Pig. Umbilical stalk not included in figure. See reconstruction Figs. 296, 318, 320. FURTHER DEVELOPMENT or THE GUT 579

tact seldom become perforated, so that no real visceral slits are formed. In occasional instances, however, such perforations do occur even in Man, as reminiscent anomalies, while in the Cow the second pair regularly develop slits for a brief period (Anderson, ’22).

The Trachea and Bronchi. — Just posterior to the visceral pouches the pharynx develops a deep ventral groove which, as in the

stomach fore- limb bud


left umbilical vein(ductus venosu§

coelom ericardial cavity

ventricle

ventral vein of mesonephros

Fig. 306.———Transverse section through the region of the stomach, liver, and posterior tip of heart of a 10 mm. Pig. See reconstruction Figs. 296, 318, 320.

Bird, is the laryngo-tracheal groove. As in that case also it shortly hecomes converted into a separate tube the trachea, which at the 7.5 mm. stage has already produced a couple of outgrowths at its posterior end. These of course are the primordia of the main bronchi, though they are commonly referred to as lung buds. At 10 mm. they in turn are just starting to give rise to stubby outpushings, the beginnings of the branchial tubes (Figs. 296, 303, 304, 305).

The Esophagus and Stomach. —— Above the trachea the part which remains after the former structure has been pinched off beneath it, is the esophagus. Between the 5-10 mm. stages a dilation develops in the enteric tube at the posterior end of the esophagus just behind the limb buds. It is the beginning of the stomach (F igs.296, 306). 580 THE TO TEN MILLIMETERS

The Liver and Related Parts. ——- In the Pig the liver primordium arises as a single rather wide diverticulum from the ventral side of the gut immediately caudal to the stomach region (duodenum) at about the 4 mm. stage. In the Bird, it will be recalled, there were two original hepatic outgrowths. The single outgrowth of the Pig, however, very

shortly gives rise to several anteriorly directed buds which grow out ,

into numerous hepatic ducts. The posterior part of the same outgrowth becomes extended as the cystic duct while its end enlarges as the gall


Fig. 307.—Reconstruction of the stomach, dorsal

and ventral pancreas and gall bladder of a 10 mm. Pig, enlarged from Fig. 296.

bladder. The anteriorly growing hepatic ducts and the posterior cystic duct remain connected with the gut by the original single outgrowth which becomes extended as the common bile duct or ductus cholcdochus (Figs. 296, 307, 308, 309). All these structures, it should be noted, do not just lie freely in the coelom, but are, as in the Chicl-:, embedded within the ventral mesentery whose existence in this region has

_ beenipreviously explained. Their development to the pointindicated

occurs between the 5-10 mm. stages.

The Pancreas. -— At about the same time that the liver diverticulum first appears (4 mm.) a dorsal evagination occurs, in this case within the‘ dorsal mesentery, and slightly posterior to the liver outgrowth. It is the dorsal part of the pancreas. At 5 mm. a single ventro-lateral pancreatic rudiment has grown out from the ductus choledochus near the point of union of the latter with the gut. It may be recalled that in the Chick there were two of these ventro-lateral. pancreatic primordia from the common bile duct,'as well as the single dorsal one. At 10 mm. each single dorsal and ventral pancreatic primordium in the Pig consists of

numerous -budding cords of cells, and the two parts are almost fusing (Figs. 296, 307, 308, 309). FURTHER DEVELOPMENT OF THE GUT 581i

The Mid-gut Region.——Immediately posterior to the liver and pancreatic diverticula the intestine of the Pig, like that of the Chick, turns ventrad. It proceeds in this direction as far as the origin of the yolk-stalk, and then passes dorsad again to the region of the rectum. By the 10 mm. stage the gut in this region has become a rather small tube,

. and its ventral bending has become a very clear cut loop whose sides

are quite closely‘ approximated. At the most ventral point of this loop,

30,53‘ Pancreas ventral vein of mesonephros

Pegterior cardinal v


posterior vena ca

8l°m hepatic portal vein

Fig. 308.——Transverse section through the region of the anterior and of the mesonephros, the bile duct and liver of a 10 mm. Fig. Umbilical stalk not included in figure. See reconstruction Figs. 296, 318, 320.

from its rather sharp apex, the yolk-stalk still takes its origin. By this time, however, this stalk is extremely constricted to form an even smaller tube than the intestine, and the yolk-sac at its extremity exists merely as a shriveled vestigial diverticulum within the body-stalk (Figs. 296, 297, 309, 310). In some instances at this time a small enlargement appears on the posterior ascending limb of the loop. It is the beginning of the caecum.

The Hind-gut Regi0n.——_,-Continuing posteriorly it has already been noted that an evagination or fold has arisen in the dorsal wall of the splanchnopleure of this region just anterior to the allantoic outgrowth to form the hind-gut (Fig. 300) . The crest of this fold is almost from the first in contact with the ectoderm above it, the fusion constituting the anal plate. Thus this plate is at first dorsal.just as in the Chick. With the outgrowth of the tail bud the caudal portion of the hind-gut region is. drawn posteriorly and ventrad. The result is that the anal 582 THE‘ PIG TO TEN LMILLIMETERS

genital ridge dorm Pancreas

posterior mrdinzl vein




I

for

ventral pancreas ventral vein of mesonephros

Fig. 309.--Transverse section through the region of mesonephros, pancreas and

posterior of liver of a 10 mm. Pig. Only a part of the umbilical stalk included in the figure. See reconstruction Figs. 296, 318, 320.

vltelline vein subcardinal veins left umbilical vein vitclline vein ’ ‘ K gut loop


umbilical arteries


ventral vcln ofmesonephros

right umbilical vein Fig. 310.——Transverse section through the region of mesonephros, gut loop, um bilical and vitelline argeries and veins, allantoic stalk and ti

p of embryo of a. 10 mm. Pig. See reconstruction Figs. 296, 313, 320. FURTHER DEVELOPMENT OF THE GUT 583

plate, as in the Bird, is presently swung clear around to the ventral side. With the further outgrowth of the tail bud a small portion of the hind-gut is pulled out into this bud a short distance beyond the anal plate. As in the Chick this extension is the postanal gut, but unlike the case of the Chick it is entirely a temporary structure with no future function, and so need not be referred to again. Both it and the anal plate, it should be noted, are nowcaudal and ventral to the allantoic stalk. Thus with the shift in these parts the latter no longer extends pos ventral vein of mesonephros

fused subcardinal veins 7 ’ ‘- \ umbilical veim


posterior cardinal vet


mesonephros 'w-- i’ - T " ‘ ’ T \. — —* ut umbilical arteries mesonephric duct

Eig. 311.— Transverse section through the region of rnesonephros, gut, umbilical veins, allantoic stalk and cloaca of a 10 mm. Pig. See reconstruction Figs. 296, 318, 320.

teriorly, but rather proceeds at first dorsad before curving antero-ventrally into the body-stalk (Figs. 296, 311). Just within the embryo postero-dorsal to the anal plate, the slightly enlarged end of the gut constitutes the cloaca, and the anal plate may now be termed the cloacal membrane. This enlarged region of the gut is called the cloaca because as in the Chick it presently receives not only the gut opening (anus), but those of the urinogenital ducts and the allantois. The opening of the anus is furthest postero-dorsal, those of the urinogenital ducts, slightly more cephalad and ventro-lateral, and that of the allantois more antero-ventral (Fig. 296). By the time this situation has developed, e.g., in a 6 mm. embryo, there has also occurred, according to some, the usual depression in the ectoderm surrounding the cloacal membrane to form the proctodaeum. The latter, though, seems not to be much in evidence at 10 mm. Thus we have a condition essentially similar to that in forms previously studied. From this point onward, however, the situation in the Mammal begins.to diverge from that previously observed. 584 THE PIG TO TEN MILLIMETER_S

The divergences just suggested, though not far advanced in the 10 mm. stage, are definitely underway, as a result chiefly of one process. Within the cloaca a crescentic sheet of tissue, the urorectal fold, is growing from the postero-dorsal wall toward the cloacal membrane and from the lateral walls toward the median line. When completed the result will be to divide the cloacal chamber into two parts. One, the postero-dorsal into which opens the large intestine, will constitute the rectum. The other, antero-ventral, part is called the urinogenital sinus, and constitutes essentially an extension of the neck of the allantois which now receives the urinogenital ducts (Figs. 311, 337). Although this change has been initiated in the 10 mm. embryo, the cloacal division is not yet complete, nor is the cloacal membrane yet ruptured as is the case with the oral plate.

MESODERMAL STRUCTURES

Under the headings of systems, we have thus far considered the nervous system, which of course is exclusively ectodermal, and the digestive system. The latter because of its lining is often thought of as primarily endodermal, though of course much of its walls are derived from mesoderm. Now, however, we are about to consider systems which are exclusively mesodermal in origin, e.g., the circulatory system, and the urinegenital system. Before embarking upon our discussion of these definite systems, however, it is also necessary to make a few further comments regarding the condition of the mesoderm in general.

The Sornites.-—— We have already discussed the origin of the lateral plate mesoderm, but there has been no occasion to refer to the somites except in a general way as criteria of development. It may now be noted that these structures develop in the Pig in almost exactly the same manner already made familiar in the Chick. As in that case the first ones formed turn out to be the most anterior, each new. one being added between the most anterior old one and Hensen’s knot. Not only is the order of their origin similar but their character and method of development is the same. Thus the original ridges of mesoderm adjacent to the notochord and nerve cord flrst become segmented. Then each segment (somite) becomes a roundish mass with the cells radiating from its slightly hollow center. Next the cells adjacent to the notochord and nerve cord become loosely arranged about these structures as sclerotome. At the same time the cells of the dorsal part of the remaining outer wall grow ventrad between this wall and the sclerotome. Thus is formed a new dorso-ventrally elongated double layered structure with THE CIRCULATORY SYSTEM 585

a space between the layers. The outer layer as before is called dermatome, and the inner wall myotome, the space between them being myocoel. The question of what these layers eventually give rise to, is still uncertain in the case of the Mammal as it was in the Bird. The inner layer certainly goes largely to form skeletal muscle, but to what extent the outer layer or dermatome really forms dermis is not so clear. Probably only part of it so behaves. The sclerotome, however, again unequivocally gives rise to the parts of the vertebrae. By the 10 mm. stage the parts of the original somites indicated above are no longer evident, except to a slight extent toward the posterior (Fig. 310).

The Intermediate Mesoderm. ——Though this term was not used in the case of the Frog and Chick its equivalent was present. It is merely the mesoderm between the somites and each lateral plate, i.e., it is the part previously designated as nephrotome. The latter term indicated its fate in the previous cases, and it is the same here. The details of this will of course be taken up in connection with the urinogenital system.

The Somatic and Splanchnic Mesoderm.——The origin of the somatic and splanchnic mesoderm, has already been discussed, and need not be gone into here. However, it is pertinent to note that by the 10 mm. stage the intermediate mesoderm on each side no longer connects the lateral sheet of that side with the disappearing somites, but throughout much of its length forms a discrete mass, the developing mesonephros (Figs. 305, 309) . As the latter pushes out into the coelom it ofqcourse carries a layer of mesoderm before it as its covering of coelomic epithelium. It thus comes about that on the median side of each mesonephros this covering passes dorso-medially until the two sheets of epithelium are separated only by the mesentery of the gut. With this arrangement the division between somatic and splanchnic mesoderm might now seem to be somewhat confused. It is customary, however, to designate only the mesodermal covering of the outer body wall as somatic. The remainder covering the mesonephros (and later the metanephros), the mesentery and the viscera is then splanchnic.

THE CIRCULATORY SYSTEM The Blood Islands. -——- It will be recalled that in the Bird one of the

first manifestations of the beginning of the circulatory system is the _

formation of blood islands in the area vasculosa, which is of course extra-embryonic. Virtually the same situation obtains in the Pig where the blood islands also appear on the surface of the empty yolk-sac corresponding to the area vasculosa of the Chick. It will be recalled that 586 THE PIG.TO TEN MILLIMETERS

in the Bird, however, the mesoderm from which they arise in this region is supposed to have migrated out from the area pellucida. It then forms blood islands, and these in turn bud 0H mesoderm cells between them and the ectoderm. No such indirect method seems to occur in the Pig. The mesoderm is already in this area, and is divided into somatic and splanchnic layers. The blood islands are then organized out of cells from the splanchnic layer between it and the endoderm. As before, these cells become aggregated into clum-ps, and while those around the periphery of each clump become flattened to form blood vessel endotlzelium, the more central ones 'transform into blood corpuscles. It should be noted also that in the Mammal this activity is not confined to the mesoderm of the yolk-sac. The allantois, which is somewhat more precociously developed than in the Bird, likewise produces blood islands in a similar manner. It has recently been demonstrated, moreover, that in certain Monkeys red blood corpuscles continue to be formed from the endothelial walls of the blood sinuses of the chorionic villi during early pregnancy (Wislocki, ’4-3). It is further claimed that in the Baboon even the amnion produces red blood cells (Noback, ’46). While early genesis of blood cells occurs in these various extra-embry . onic locations their later formation is relegated to special organs such

as the mesonephros, liver, spleen and finally the bone marrow. Meanwhile the differentiation of the endothelium of numerous vessels goes on constantly throughout the embryo. As the circulatory system thus develops it is quickly supplied with both corpuscles and fluid from the various blood islands, and later from the other sources just indicated. Whether these later centers possess their capacity as a result of the migration to them of blood forming mother cells from the original blood islands is still an open question. Some hold this view, while others maintain that the later centers give rise to their own blood-forming cells from local mesoderm. Possibly both methods occur. In any event there are of course many kinds of blood cells produced from the original mother cells, and their varied diiferentiations make a complicated subject which we shall not go into. '

The Heart. — One of the first parts of the intra-embryonic circulatory system to develop is the heart, and the method of its early formation is virtually identical with what we have already described in the Chick. On either side of tlie pharyngeal region, before this part has been closed in ventrally, the endothelium of a blood vessel forms between the splanchnic mesoderm and the endoderm in the manner described above. As the closure occurs these two blood tubes fuse beneath the pharynx to THE CIRCULATORY SYSTEM 587

4 t t 6 dorsal acme truncus arterloxus somlte posterior cardinal veln


vitelline (omphalomesenteric) veins

amum duct of Cuvier

1 anterior cardinat vein i truncus arteriosus

_' . - g”


dorsal aortae



vitelline(omphalomesenteric)veins, arteries

Fig. 312.—A. Partial injection of the vessels of a Pig embryo of 14- somites, 4‘ mm. in length. After Sabin. B. Partial injection of the vessels of a Pig embryo of 1 27 somites, 6 mm. in length. After Sabin. 588 THE PIG TO TEN MILLIMETERS

form the usual single heart tube. The splanchnic mesoderm follows the endothelium and while the latter constitutes the endocardium, the mesoderm covers it to form the epicardium, and the dorsal and ventral mesocardia. Because of the latter the two coelomic spaces on either side (_in the Bird called the amnio-cardiac vesicles), as in that case, do not at first communicate. Presently, however, the ventral mesocardium disappears, and the two parts of the pericardial space are united. The dorsal mesocardium, as in the Chick, persists somewhat longer. This condition is reached at about the 4.5-5 mm., or 13 somite stage. (See Chick, Fig. l 79.)


Fig. 313.—Frontal section through the heart of a 10 mm. Pig.


The next steps in cardiac development in the Pig are again very familiar. The dorsal mesocardium in its middle region disappears, leaving the double-walled tube free to bend. Then as the latter increases in length it becomes thrown into the usual curve to the right, and this shortly becomes a loop whose apex is rotated backward. As in the Chick, the postero-dorsal part of the loop becomes the atrium, the apex of the loop and a portion of each limb the ventricle, and the antero-dorsal end of the more anterior limb the truncus arteriosus. These parts then rotate so that the atrial region becomes antero-dorsal, and the apex of the ventricle postero-ventral with the truncus running cephalad along the antero-ventral face of the ventricle. From a comparison of this description and of the figures of the heart of the Frog and Chick at similar stages the essential Ilikeness will be apparent (Figs. 108, 184-, 312). By 10 mm. the befidings and shiftings indicated above are complete, and the heart presents externally almost the adult appearance. Internally a crescentic septum, the septum primum (I) has grown from the antero-dorsal wall of the atrium, and has partially divided it into right and left chambers. Postero-ventrally, i.e., toward the ventricle, however, the growth is not quite complete, and the very small opening briefly remaining is all that is left of the originally wide-open orifice between the atria, the interatrial foramen primum (Figs. 313, 314). Meanwhile dorso-anteriorly a new opening has developed in the septum called the interatrial foramen secundum. Also another septum, the septum secunclum (II), is sometimes slightly in evidence to the right of the septum primum (Fig. 313). The further fate of these septa, their openings and their functions will be fully discussed in the section on ‘later development. Another conspicuous structure apparent within the right atrium at 10 mm. is a pair of flaps guarding the orifice from the sinus venosus to this atrium, the valvulae venosae (Fig. 304). Later on one of these valves forms a minor ridge, the septum spurium, which soon disappears.


Fig. 314.-—Reconstruction_of the heart of a 7.9 mm. Fig with the right atrium and right ventricle opened from the right side. After Morrill.


Between the atrium and the ventricular region the heart is somewhat constricted to form the atria-ventricular canal, and this also has become almost or quite divided by growths proceeding from its dorsal and ventral walls. When complete these growths, as in the Bird, will form the so-called cushion septum (Fig. 304). At the same time a third septum, the interventricular, is growing from the apex of the ventricle toward the atrio-ventricular canal (Fig. 304). All these septa will shortly meet to divide the entire organ into completely separated right and left chambers, save for the existence of one of the interauricular foramina which persists until birth and even after. Finally the walls of stages of development as indicated by the number of somites are not always exactly correlated with the relative lengths of the embryos. The former is usually the more accurate criterion of degree of general development in the earlier stages. Hence both items are given.


Fig. 315.—St_ages in the development of the aortic arches and other anterior ar . 4.4 mm., 10 somites. B. 4.15 mm., 19 somites. C. 3.8 mm., 26 sornites. D. 4.57 mm? 28 somites. E. 4.46 mm., 30 somites. F. 6 mm.,



Fig. 316.—Stages in the dgvelopment of the aortic arches" and other anterior arteries of the Pig. After Heuser. A. 24 somites. B. 4.3 mm., 26 son-mites. C. 6 mm., 36 somites. D. 8 mm. E. 12 mm. '


Fig. 317.—-Stages in the development of the aortic arches and other anterior arteries in the Pi . After Heuser. A. 12 mm. B. 14 mm. C. 17 mm. D. 19.3 mm.


the ventricles become definitely thickened, and muscular bands, the trabeculae carneae project into the ventricular lumen.

The Truncus and Aortic Arches. ——.The truncus arteriosus has already been mentioned as it comes up underneath the pharynx. As in



F:g.3oz I RF?th|<e's pockeg pulmonary artery I 9"”: vertebralarter Ii: Interatrigfomcn V subciaviaingdrtery ’ fi"3°“


Fig. 318. —-—Reconstruction of a 10 mm. Pig embryo designed to show primarily the main features of the arterial system at this stage. Drawing made by same methods as used for Fig. 296. As before the lines at the sides indicate where the sections denoted by the figure numbers above the lines, pass through the embryo.

the case of the Chick this large vessel does not, contrary to what most diagrams suggest, really extend any distance cephalad in a horizontal position before giving off the aortic arches. Instead it extends dorsally and only ‘slightly cephalad directly into the -midst of the pharyngeal region (Fig. 318). Here it gives rise to the six aortic arches, but again as in the Bird, not all at one time. The mandibular aortic ‘arch appears first, then the hyoid, and by the time the other four pairs have developed in

the remaining visceral arches (10 mm.) the first two aortic vessels have _

disappeared (Figs. 315, 316). Also again as in the Chick, the‘ fifth pair 594 THE PIG TO TEN MILLIMETERS

are vestigial, sometimes appearing briefly as loops on -the front sides of the sixth arches, and sometimes on the posterior sides of the fourth. With respect to the sixth arches themselves it must be noted that as early as 7.5 mm. each has given rise to a small posterior outgrowth which



Fig . 319.——Semi-diagrammatic representation of the development of the aortic

arc es and other anterior arteries of the Pig. A. Arteries at the 10 mm. stage. B. Arteries of a specimen near term.

left subclavlan artery

reaches the developing lung buds. These outgrowths, together with the proximal parts of the arches, constitute at the 10 mm. stage the pulmonary arteries (Fig. 316, E). It may be noted that in other Mammals studied the proximal parts of both the sixth arches continue to form a part of these arteries. In the Pig, however, as we shall see, only the proximal part of the left sixth arch persists as a part of the pulmonary system (Figs. 317, A, B; 319). Anteriorly, the first two pairs of arches THE CIRCULATORY SYSTEM 595

have disappeared, and each member of the third pair has given rise near its base to a new vessel. These vessels are the external carotids, and appear at lffmm. as very tenuous strands extending cephalad toward the

ventral part of the head (Fig. 318). Both fourth arches at this time remain well developed.

The Dorsal Aortae. —— At their dorsal ends the arches of each side are connected anteriorly and posteriorly by the two dorsal aortae. Cephalad these aortae remain separate, and extend into the head as the internal carotids. Posteriorly they also continue separately at first (Fig. 312, B), but at about 6.5 _mm. (17 somites) they become united at ap proximately the middle of the embryo to form the single dorsal aorta. '

By the 10 mm. stage this fusion has progressed to the tail, and as far forward as the anterior appendages (Figs. 316, 318).

Other Arteries Anterior to the Heart.——ln the Pig and other Mammals the internal carotids are not the only dorsal arteries extending into the head. There early arise from the aorta throughout most of its length small branches between each pair of somites, the inter segmental (or segmental) arteries. These were also noted in the Chick. In the Pig, however, these arteries soon form antero-posterior anastomoses

in the region extending from the seventh cervical somite into the head,‘

and at the same time lose their connections with the dorsal aorta. As a result of this process there are established in the neck region anterior to the seventh cervical intersegrnental arteries, a pair of longitudinal vessels called the vertebral arteries (Fig. 317). These arteries, however, do not continue separately clear into the head. Beneath the myelencephalon they fuse into a single median vessel termed the basilar aitery. As re - gards the seventh cervical intersegmentals, it may be noted that they are

starting to enlarge slightly to take part in the formation of the subclavian arteries, whose development will be described further in the next stage. The fate of the intersegmentals posterior to the seventh cervical will also be noted at that time. Meantime by the 10 mm. stage the internal carotids have each sent a branch medially to unite with the basilar, thus producing a part of the future circle of Willis about the hypophysis (Figs. 317, 318, 319).

Arteries Posterior to the Heart.—To complete the history of the arteries at this stage we find that somewhat caudad from the middle of the embryo, the two omphalomesenteric or vitelline arteries are among the first to‘ arise from the dorsal aortae. These arteries connect the aortae with the vessels formed in the wall of the yolk-sac, and since the vitellines arise before the dorsal aortae have fused, they are at first double (Fig. 312, B). Their function of course is to take blood from the embryo to the yolk-sac, where it receives nutriment absorbed by this organ from the uterine walls prior to the development of the allantoic placenta. At 10 mm. the aortae in the region of the origin of the vitelline arteries have fused and with them the arteries, so that a single




fig. 299

j H9299 anterior cardinal vein external jugular vein Fig-302 F:‘g.302 right duct of Cuvier valvulae venosae I-75.304 Fig. 301! “CW5 V¢"°‘"‘ omphalornescnteric vein Fig-305 Fig.305 posterior vena cava Fi .306 Fig. 306 right hepatic vein _

p;s_3o8 Fig. 303


Fig. 320.——Reconstruction of a 10 mm. Pig embryo designed to show primarily the main features of the venous system at this stage. Drawing made by the same methods as used for Figs. 296 and 318. As in these figures the lines at the sides indicate where the sections denoted by the figure numbers above the lines, pass ‘throughthe embryo.

vitelline artery extends along the mesentery into the body-stalk (Fig. 318). With the disappearance of the yolk-sac this vessel persists within the body as the anterior mesenteric artery. A short distance anterior to it the coeliac artery has developed at~10 mm., and extends toward the stomach region, but the posterior mesenteric artery has not yet appeared. In addition to the segmental arteries already mentioned the aorta also gives off numerous small’ branches at the level of the mesbnephros to the glomeruli and tubules of that organ, the renal arteries. Lastly, so far

as branches from the aorta are concerned, are the umbilical arteries to 2 . THE CIRCULATORY SYSTEM 597

the allantois. These arise quite early before the two aortae have fused in this region, and even after their fusion at 10 mm. the umbilicals rernain separate. By this stage also each has produced a small branch in


Fig. 321.—Reconstructions of stages in the development of the veins of the liver and immediate vicinity. A. The veins in a. 5-6 mm. embryo, semi-diagrammatic. Veins in the liver according to Butler, with the omphalomesenteric (vitelline) veins extended posteriorly to show their relation to the gut. B. Veins in a 6 mm. Pig embryo, semi-diagrammatic. Again the vessels within the liver are according to Butler, with the omphalomesenterics posterior to it added. C. Veins in the liver of a 10 mm. Pig embryo viewed from the right side (enlarged from Fig. 320). D. Veins in the liver of a Pig at the same stage as C, but viewed ventrally.

connection with the developing hind limb bud, the external iliac. The aorta itself continues on as a single vessel into the tail (Fiv. 318).

, The Omphalomesenteric Veins.—As in the Bird, among the i earliest, if not the earliest, veins to develop in the Pig are the am phalaA mesenteric or vitelline veins. They. arise just as they did in the Chick coincidentally with the formation of the cardiac tubes which fuse an-_ teriorly to form the heart. Posterior to the region of fusion these tubes extend caudad and laterally out onto the yolk-sac where _theyi’become continuous with the capillaries and blood islands which we have noted

ventral vein 0! mesonephrot

posterior ardlnnl veln

-right subcardlnal vein

Early stage in any young 5-6 mm. Fig embryo. mammalian embryo.

sinus venesus


anterior ardlnal vein duct of Cuvler

subclavian Vein

posterior ardlnal vein

I I rlghl umbilical vcln e E umbmal "In

hepatic portal vein

3-7 mm. Fig embryo. 12-14 mm. Pig embryo.

Fig. 322.--Diagrams of developing venous system posterior to heart in: A. Any very young mammal; B, C, E, F, H, I, J, in Pig at stages indicated. D. Transverse section of C at level shown by arrow.

as originating there. As development proceeds the fusion of the vitellines continues for a very short distance posterior .to the atrial region of the heart to form a thin walled sac, the sinus venosus (Figs. 312, A; 322, A, B); At about this time also (3.5—4 mni.) the previously noted interatria prirrium begins to develop, and in such a way that the sinus l ._ 'j‘,e*‘6pa1-in\to"“l:Z1e right atrium (Fig. 304). K.


Fig. 322 cont.—F, H, I, J, as noted ahove. G. Transverse section of F at level shown by arrow. All stages after Butler. Princeton Embryological Collection.

At this point a difference may be noted between the further development of the vitelline veins in the Chick and that in the'Pig. The two veins in the Pig do not continue their fusion to form may large part of the ductus venosus as in the Bird, the major portion of that trunk arising from a different source in a way to be described be ' remain mostly separate, the liver and pre ' fl t9-fie 600 THE PIG TO TEN MILLIMETERS

stage their middle portions have broken up into a capillary network. Their anteriorstumps, however, remain as the two hepatic veins, while their posterior parts persist for a time in the caudal half of the liver as two distinctuvessels (Fig. 322, A, B). From there these vessels issue to pass along either side of the gut to the regressing yolk-sac. As the latter

disappears they become simply two veins bringing blood from the intes tine, and by the 10 mm. stage a further change has occurred, resulting in the reduction of these two vessels to the one hepatic portal vein. The method by which this takes place, producing the peculiar spiral course of this single vessel about the gut, is illustrated in figure 321. It involves essentially the same process as in the Chick, i.e., a fusion of the vitelline vessels first above the intestine, and then below it, with the subsequent disappearance of the left and right sides of the loops thus formed. The chief diiierence between the Chick and the Pig in this connection is that in the latter both sides of the loop are formed before ei ' ther disappears, but as indicated the end result is the same.

The Allantoic (Umbilical) Veins. —— Another pair of veins which develop very early in the Mammal are the allantoic or umbilical veins. In the Bird these are somewhat slower in forming, and it will also be recalled that at first the allantois is drained by a transitory vessel, the subintestinal vein, which opens anteriorly into the vitellines. This preliminary arrangement does not occur in the Pig. Instead the umbilical veins develop at once in essentially the same way that they ultimately do in the Bird. They arise as vessels in the lateral body wall which open anteriorly directly into the sinus venosus (Fig. 322, A). Posteriorly they extend around the sides of the wall, and thence via the bodystalk onto the neck of theallantois (Fig. 273). This is the situation at first, but by 10 mm. certain changes have developedas follows: Anteriorly the two veins no longer empty directly into the sinus venosus. Instead as the liver comes into contact with the body wall, the umbilicals in that wall develop new channels connected with the hepatic capillaries (6 mm.) (Fig. 322, B). By the 10 mm. stage some of these capillaries in line with the flow of blood from the two umbilicals have developed into well marked channels which soon become definite vessels within the liver. The left one even at this stage is larger than the right, which soon disappears in this region. Hence the part of the left umbilical within the liver now forms the major part of the ductus -venogms, the short anterior section which opens into the sinus, being derived from the very limited fusion of the vitellines indicated above (Figs. 320, 321, 322, C). Thus, as noted, the ductus has for the most part a quite difl'erTHE CIRCULATORY SYSTEM 601

ent origin from the similarly named vessel in the Chick where it arose entirely from the posterior fusion of the vitelline veins. Caudad to the liver the two allantoic or umbilical veins continue at this time to exist as separate vessels as far as the umbilical stalk, but within this stalk they have become fused into one. Thus there is but one umbilical vein in the stalk, but two umbilical arteries. Even at this stage, however, the right umbilical vein within the body wall is becoming smaller.

The Anterior and Posterior Cardinal Veins. —— So far we have considered venous systems which are both intra- and extra—embryonic. It now remains to indicate the development of those veins which are entirely within the embryo. Among these the most prominent up to the 10 mm. stage are the various cardinals, whose development very closely parallels that in the Bird. Thus the anterior cardinals arise anteriorly on either side of the neck and headregion slightly dorso-lateral to the aortae, and soon develop a capillary network connecting with the latter vessels. The posterior cardinals likewise develop in the same relative position to‘ the aorta posterior to the heart. Dorso-lateral to that organ the anterior and posterior vessels of each side dip.downward slightly, and join one another to form the wide, short ducts of Cuvier which slope ventrally and medially to enter the sinus venosus. A short distance cephalad to the point where the anterior cardinals enter the ducts each cardinal is joined by a ventral branch coming from the region of the mandibular arch. It is of course the future external jugular. Very slightly posterior to, or at its junction with, the respective duct of Cuvier each posterior cardinal receives the subclavian from the adjacent forelimb bud. This vein, as was the case with the corresponding arteries, results simply from the enlargement of one of the numerous intersegmental veins which drain into the posterior cardinals (Fig. 321, 304).

The Subcardinals and Posterior Vena Cava. ——Again as in the Chick, with the development of the mesenephros the original cardinal circulation is supplemented by certain new vessels which in a 10 mm. embryo are well established. Indeed by this time the posterior cardinals have actually begun _to degenerate, and their functions to be taken over by these new vessels as follows:

Along the ventro-medial border of each mesonephros a plexus of capillaries is formed (5-6 mm.) , and soon these have anastomosed so as to constitute continuous vessels running the length ‘of each mesonephros. These are the subcardinals, and through further mesonephric capillaries they are soon more or less connected with the posterior cardinals‘ (Fig. 322, B). In fact anteriorly these connections presently become quite 602 THE PIG T0 TEN MILLIMETERS

definite and direct. Now as the mesonephroi grow the suhcardinals are crowded still nearer the mid-line, and at about the middle antero-posteriorly, ofthe mesonephroi they fuse into a single large sinus (Figs. 311, 322, C, D, E). Into this drain all the surrounding capillaries. This comes about because, as this sinus is formed, the posterior cardinals at this level disappear entirely, though they persist for a time both anteriorly and posteriorly. Thus it happens at 10 mm. that among the capillaries draining their blood into the median subcardinal sinus through the mesonephros are many from the posterior parts of the posterior cardinals (Figs. 320, 322, C, E). At the same time anterior to the subcatdinal sinus, the left subcardinal begins to become smaller, and to lose its connection with the anterior part of the left posterior cardinal, though this is still functioning at 10 mm. (Fig. 322, C, E). The right subcardinal, however, just as in the Bird, becomes more prominent, and at 10 mm. has affected a connection with still another new vessel. This vessel has formed from capillaries within the liver mesentery, and also from some of those within the liver itself. It is the mesenteric and hepatic part of the posterior vena ctwa, the subcardinal sinus and the anterior portion of the right subcardinal, being the other parts developed at this time (Figs. 320, 322, C, E). Anteriorly the part of the new vessel developing in the liver opens into the ductus venosus near its anterior end, where it also receives the two hepatic veins. As the caval vein grows, the anterior part of the ductus between this vein and_ the sinus becomes the anterior end of the vein (Fig. 321). The complete development of its posterior end will be explained in our discussion of the next stage.

In connection with the description of this vessel up to the present point, however, there is, already one feature concerned with its posterior part which is becoming evident, and which merits attention. This feature is the development of a renal portal system in essentially the same way that it was formed in the Bird (Fig. 322, E). When fully developed, these systems function more or less like that of the Frog, though they arise somewhat difierently, there being no subcardinals in the Frog.‘ It is interesting of course that this system exists in all these forms, yet in the Bird and Mammal is only temporary. It is perhaps even more remarkable that it is always the right side (in the Bird and

1 It appears that in the Pig,‘ and very probably the Bird, not so much of the blood coming from the posterior of the embryo is actually supplied to the mesenpheric tubules as in the Frog. Instead more of it seems to be routed more directly

through the organ, while the tubules, as well as the glomeruli, are supplied more from arterial sources.


Mammal the right subcardinal (in the Frog the right posterior cardinal) which enters into the formation of the posterior vena cava. Such facts can scarcely be entirely coincidental.

One minor feature regarding the cardinals in the 10 mm. Fig which differs from that in the Chick should be mentioned to avoid confusion. In the Chick there are no other vessels than those just described. In the Pig, on the other hand, some of the capillaries along the ventro-latera-I side of each mesonephros also anastomose to form a small vessel extending antero-posteriorly along this region. It is called the ventral vein. of the mesonephros, and since it also connects through capillaries with the respective posterior cardinal, it might be mistaken for a subcardinal. Its smaller size and superficial ventral position, however, distinguishes it and it soon disappears (Figs. 320, 322, C, D, E).

The Pulmonary Veins.-—0ne other important intra-embryonic venous system which has no relation to the cardinals, but which also starts to develop at an early. period is the pulmonary. Since the pulmonary arteries have been seen to arise as early as the 7.5 mm. stage, the development of the veins at about that time might be anticipated, and they have in fact arisen. There is some question, however, as to just how these vessels have been formed, e.g., whether as an outgrowth from the atrium, or as in so many other cases, by an anastomosing of plexuses along their course. In any event they exist at this stage as small

i veins which proceed from each lung bud, and unite in a common trunk which enters theleft atrium. Later as in the case of the arteries the pulmonary veins also suffer certain alterations which will be noted in due course.

THE URINOGENITAL SYSTEM

Although these systems are ordinarily considered together because of the close association of some of their parts both embryologically and anatomically, it is convenient as previously, to describe their development separately. We shall begin with the excretory systemsince it is the first to become clearly evident.

E THE EXCRETORY SYSTEM

I The Pronephros. —— In the Pig, as in the Bird, there is a gesture made toward the development of a pronephros. On-each side its rudimentary tubules arise as usual from the intermediate mesoderm, and occur in the cephalic region from about the sixth to the fourteenth somites. These vestigial organs are of course without functional significance, but

I . ‘T

604 THE PIG TO TEN MILLIMETERS

the tubules turn and grow caudad to give rise to the pronephric ducts, in the way with which we are already familiar. By 10 mm. all parts of this system, save the ducts, have virtually disappeared. , _ The Mesonephros.—The mesonephros arises in the intermediate ‘ mesoderm from about the fourteenth to the thirty-second somite of the I Pig.‘ As usual it first appears as spherical concentrations in this meso- ' ii derm, three or four such concentrations being developed opposite each somite. These form vesicles, and the vesicles produce tubular outgrowths which become coiled, and open into the old pronephric, now mesonephric, duct. The vesiculariportion of each tubule is invaginated by the usual knot of capillaries forming a glomerulus, supplied with blood by branches from the aorta, and draining into tributaries to the subcardinal veins. The invaginated part of the tubule of course constitutes Bowman’s capsule. Anteriorly the mesonephric duct is often difficult to distinguish in cross section from the numerous mesonephric tubules, but more caudally it can generally be located along the ventral border of the organ. Poste rior to the mesonephros this duct continues to the cloaca, and by the 6 mm. stage has entered it. By 10 mm. the antero-ventral region, into the sides of which this entrance was affected, is beginning to be separated from the postero~dorsal part by the urorectal fold in the manner already described (Fig. 337). Thus the ducts are coming to open into the part of the cloaca termed the urinogenital sinus which is in the process of being added to the neck of the bladder (allantois). These arrange— ments in the cloacal region are the beginnings of changes which will ultimately bring about fundamental diflerences between conditions in these parts in the Bird and the Mammal. These dilierences will be discussed in detail later in connection with the development of the external genitalia. At this time, however, the most striking peculiarity of the mammalian excretory system lies in the remarkable relative size of the mesonephroi themselves. Thus in a 10 mm. Pig these organs are far larger than at any period in the Chick, being in fact much the largest structures in the embryo (Figs. 296, 310, 311).-The functional significance of this difference is not known. The Metanephros and Ureter. ——As the student is already aware, the mesonephric kidney in all Amniotes is ultimately replaced by a third or metanephric kidney. This kidney starts to appear at the 5-6 mm. stage as a very smalldiverticulum growing out from the posterodorsal side of each mesonephric duct just dorsal to the point where if these ducts enter thelcloaca. By 10 mm. the diverticula still issue from the mesonephric ducts rather than the neck of the bladder, but have grown anteriorly somewhat, and the cephalic portion of each is enlarged slightly. The enlarged portion represents the lining of the future pelvis of the kidney, and is already surrounded by a concentration of intermediate nephrogenic mesoderm (Figs. 296, 323). This mesoderm is carried forward with the pelvic portion, and later furnishes the material from which the kidney tubules are made. The remainder of the outgrowth of course becomes the future metanephric duct or ureter.


Fig. 323. —Transverse section through the region of the mesonephros, umbilical arteries, mesonephric and metanephric ducts and hind limb buds of a 10 mm. Pig. See reconstruction Figs. 296, 318, 320.


The Genital System

The Gonads. These are barely in evidence at the 10 mm. stage. They may sometimes be detected, however, as very slight thickenings on the medial sides of the mesonephroi, somewhat anterior to the middle. 16

THE LATER DEVELOPMENT OF THE PIG

HA V I N G completed our descriptions of the Pig embryo as a whole, and of the various systems at the 10 mm. stage (20—21 days), we are now prepared to indicate the further development of this animal as far as it is profitable to carry it. This means in most instances, either to the adult condition, or to a condition near enough to it so that the ‘steps required to attain the adult state are quite obvious. As in the discussion of the earlier development we shall begin by a consideration of external features. E ' '

The Flexures. — Following the 10 mm. stage the Pig embryo grad ually straightens to some extent. "This pr'ocess first involves mainly the dorsal flexure (15-20 mm., Fig. 324), and later the cervical and lumbesacral flexures. As in other vertebrates the cranial flexure is permanent, but since it concerns chiefly the brain it also ‘becomes less obvious externally as development proceeds.

External Features Posterior to the Head and Neck Region. —At 15 mm. the boundaries of the somites are still clearly visible, and the milk ridge has become evident. By 20 mm. the ,somite markings have pretty much disappeared, while along the lower border of the milk ridge fiveior six mammary anlagen are present. Ventral to these anlagen in both these stages the abdomen protrudes greatly, due to the developing mass of viscera within it. By the 50 mm. stage, however, these have been drawn up, and the ventral contour is about _that of a well-fed adult. Throughout all these periods there has been relatively little growth of the umbilical cord. Its diameter does ultimately increase, however, due to growth of the contained blood vessels and connective tissue, so that at term it measures from 8-10 -mm., while the length of the whole animal may be as much as 25-30 cm. The paddle-like appearance of the feet at 10 mm. has been referred to, and this condition still prevails at 20 mm. By that time, however, the existence of five toes in each foot is clearly in evidence, and the limb joints are slightly suggested. In the Pig and other Artiodactyls, as is well known, the first digit (homologue of the thumb or great toe in Man) soon vanishes entirely. The third and fourth digits develop evenly to form the cloven hoof, while the second and fifth digits remain short and more or less vestigial. This condition is well advanced in an embryo of 40-50 mm.

The Head and Neck Regions. — Probably the most striking changes of all in any mammalian embryo are those connected with the head and neck, especially with relation to the face, and we shall now indicate these changes in their main outlines.


Fig. 324. +A 20 mm. Pig embryo viewed from the right side.

When last described at 10 mm. it will be recalled that there were four visceral clefts and four arches visible in a side view, the first arch being the mandibular (Fig. 294). Also apparent were the maxillary processes and nasal pits. Each pit was bounded laterally by a nasclateral process which was separated from the adjacent maxillary process by'a groove running from oral cavity to eye, the lachrymal groove. Viewed anteriorly (Fig. 295) the frontal process separated the nasal pits, and adjacent to each pit this process was thickened to form the naso-medial processes. Reference to the appropriate figures makes evident the great similarity of these facial anlagen in a 4-5 day Chick and a 10 mm. Pig. It may now be added that the resemblance between Pig and Man at comparable stages is even closer. Indeed the latter are so much alike not only with regard to facial features, but in other respects, that to a casual observer the differences between a 10 mm. Pig embryo and a 10 mm. Human embryo would be scarcely noticeable. The changes which gradually ensue to produce the condition in the head of the adult Pig will now be indicated.


naso-lateral process naso-lacrymal groove naso-medlal process

eye external naris

maxillary process

mandibular arch tdngue

auditory opening

Pl"“3 °f °a" (hyomandibular cleft)

Fig. 325. A view of the face of a 17 mm. Pig embryo from the antero-ventral side. '

The lower jaw, it may at once be noted, is derived entirely from the mandibular arches which grow antero-medially until they meet. Posteriorly they form an angle with the maxillary processes which constitute the larger part of the upper jaw. However, these latter processes do not meet one another anteriorly, and hence do not form the antero-median part of this jaw. Instead this part is comprised of the naso-medial processes whose forward extremities grow together. In so doing they crowd the original median region, i.e., the frontal process, backward (Figs. 295, 325). Thus the naso-medial processes come to form the pre-maxillary part of the upper jaw, and the nasal septum, while the frontal process forms only the nasal bridge. While this fusion between the naso-medial processes is occurring in tlie mid-line, each of these processes is also fusing postero-laterally with the respective maxillary process, and also with the respective naso-lateral process. These fusions serve to bound the nasal pits antero-laterally, and cut them off from the edge of the oral cavity, thus producing the external nares (Fig. 325). Posteriorly these pits breakthrough into the oral cavity, and so give rise to the temporary internal nares, of which more will be said in connection with the development of the mouth proper. While the bridge of the nose is formed as noted from the frontal process, its sides (alae) are constituted by the naso-lateral processes. Also the lachrymal groove separating these processes from the maxillary processes is closed over so as to form a tube, the lachrymal duct connecting eye and nose.

Further development of the Pig’s face consists largely of the outgrowth of all these parts. Indeed the whole procedure from 10 mm. onward may be roughly pictured thus: It is much as though all the above processes were approached from the front by invisible fingers which grasp these processes, squeeze them together, and then draw them out anteriorly to make the Pig’s snout. Essentially these same changes occur in the development of the human face from the same original parts, except that, fortunately from our point of view, the “ drawing out ” procedure is not carried to such an extreme. It is of some interest to note in this connection that a failure in the fusion of the naso-median processes with the respective maxillary processeson one side or both results in the formation of the defect known as “ harelip.” An inspection of Figure 325 will show why this is true.

On the sides of the head the almond shaped eyes do not possess lids,

even at 20 mm., though the follicles of the coarse bristles constituting the Pig’s eyebrow _a_re,, clearly visible. Both upper and lower lids appear very shortly, however, ‘at about 24 mm., as folds of skin. Eventually these folds meet and fuse so that the eye is completely covered for a time, and in some animals this condition even persists for a while-after birth, e.g., in the Cat, in which case the animal is said to be born “ blind.” As regards the eye itself, it has previously been indicated that one prominent difference between the Chick and the Mammal is the fact that in the earlier stages the eyes of all mammalian embryos are definitely smaller than those of comparable Bird embryos. This is still true at the stage of the latter corresponding to that of the 20 mm. Pig, and it may be further remarked that the Pig eye is even smaller relatively than that of many other Mammals, e.g., Man pr Rat.


The Nervous System

In the preceding chapter the development of the nervous system was carried to the point characteristic of a 10 mm. Pig, and in so doing it was found convenient to treat it by parts. These involved the brain, the neural tube, the cranial nerves, the spinal nerves and the organs of special sense. We shall now proceed with the further development of these parts so far as seems profitable.



Fig. 326.—Lateral views of two stages in the development of the Pig brain. In B the corpora quadrigemina are entirely covered by the cerebrum and cerebellum.


The Brain

The Telencephalon

This structure is of course the anterior part of the prosenoepharlon which is separated from the posterior part (diencephalon) by the same boundaries already familiar in the Chick. As previously noted it has already started to give rise to its most important and conspicuous products, the cerebral hemispheres. As in the Chick THE BRAIN 611

these antero-lateral outgrowths contain cavities, the lateral ventricles, which communicate with the small remaining space within the telencephalon by the foramina of Monro. This latter space as usual constitutes a small part of the anterior portion of the third oentricle.

It was noted in the discussion of this region in the Chick, that although the cerebral hemispheres are relatively prominent structures in that form, they never attain the size and complexity characteristic of the Mammal. In the latter animal their size eventually causes them to constitute by far the larger part of the brain, and to cover entirely the mammalian homologues of the Bird’s conspicuous optic lobes. In addition to their mere size, in the Pig and most other higher Mammals, their surface area (cortex) is increased by complex foldings, the narrow depressions or fissures between the folds being known as sulci. It should now he noted that one of the more conspicuous of these sulci extends horizontally along the ventro—lateral region of each hemisphere, serving to separate the upper portion, or neopallium, from t.he lower portion or rhinencephalon. It is therefore called the sulcus rhinalis. Other sulci within the neopallium serve to divide it into the frontal, parietal, temporal and occipital lobes or regions, which in turn are still further subdivided (Fig. 326). The rhinencephalon does not contain conspicuous sulci, but does give rise at its anterior extremity to the olfactory lobes or bulbs, while its lateral walls constitute chiefly the pyriform lobes. Quite evidently the.rhinencephalon is phylogenetically the older part of the telencephalon, while the neopallium is a recent addition reaching its most conspicuous development in Man.

The Diencephalon

This posterior portion of the prosencephalon, whose laterally compressed cavity comprises most of the third ventricle, has already been noted as giving rise to the optic vesicles and infundihulum. The connection of the optic stalks with this part of the brain is marked as usual by the optic recess which really constitutes the ventral boundary between telencephalon and diencephalon. Immedi p ately posterior to this recess and hence definitely in the wall of the di encephalon, is a thickening which, as in the Bird, is the optic chiasma, within which eventually the fibers of the optic. nerves cross each other. Adjacent to the chiasma on the posterior side (i.e., the floor) occurs a thin region of wall termed the lamina post optica, and immediately beyond that the pouch-like infunklibulum presently makes contact with Rathke’s pocket growing antero-dorsally from the stomodaeum. As previously indicated these two latter structures together produce the adult pituitary or_ hypophysis. The anterior part of this organ, comprising the pars distalis, pars intermedia and pars tuberalis, is derived entirely from Rathke’s pocket, while the posterior part forming the pars nervosa. and the stalk are derived entirely from the infundibulum.


Upon the anterior side, i.e., the roof of the diencephalon, two structures appear. The more posterior, or really dorsal, is an outpushing whose lumen later becomes occluded, and which develops into the epiphysis. Anterior to this the rather thin roof of the third ventricle becomes invaginated, and this invagination divides into two parts which extend forward into each lateral ventricle. These invaginations or folds are partially produced and augmented by the development of blood capillaries within their walls, and they thus come to constitute the anterior ‘choroid plexus or plexuses.

The sides of the diencephalon. are eventually thickened to form the optic thalami, the thalami of each side being connected by a median fusion of the walls. The transverse band of tissue formed by this fusion is called the massa intermediu.

The Mesencephalon

As previously indicated, the roof of this region, which in the Bird forms mainly the optic lobes, in the Mammal gives rise to the corpora quadrigemina. As the name suggests, these consist of four, instead of two, thickened outpushings which, as already noted, are well covered in the adult by the large cerebral hemispheres. The more anterior pair are apparently more or less homologous in function with the avian optic lobes, and might be so named, but are not. Instead they are called the superior colliculi. The posterior pair are cen s ters for auditory reflexes, and hence might be referred to as auditory

lobes, but again their actual names are the inferior colliculi. The sides and floor of the mesencephalon become greatly thickened by fiber tracts connecting the anterior andposterior parts of the brain. In the Bird they were designated as the crura cerebri, though this term is not so commonly employed ‘in the Mammal. Here these regions are often referred to as peduncles. At all events the growth of these parts com-4 presses the lumen of this region of the brain into a narrow canal connecting the third and fourth ventricles, and universally termed the aqueduct of Sylvius.

The Rhombencephalon

It will be recalled that in the Mammal, as in the Bird, thenposterior part of the brain, i.e., the rhombencephalon, is early divided into two parts, the anterior metencephalon and the posterior myelencephalon. The former is the shorter region, and indeed consists primarily in itsdorsal aspect of the thickened ‘sloping roof of the posterior side of the isthmus fold (Fig. 297). As in the Chick this dorsal region presently undergoes extensive growth to form the cerebellum, a part of the brain especially concerned with muscular coordination. The division of this organ into a median lobe, the vermis, and lateral lobes, which appeared to some extent in the Bird, is still further emphasized in the Mammal, and in addition each lobe develops, extensive foldings (Fig. 326). Ventro-laterally beneath the cerebellum the walls of the metencephalon are greatly thickened by fiber tracts, partly from fibers originating in the cerebellum itself, and partly from fibers passing through these walls to and from anterior parts of the brain. In this region, as in the mid-brain, the thickenings so caused are often designated as peduncles. The ventral thickening becomes so pronounced eventually as almost to comprise a sort of reversed flexure. It is called the pans, and because of the eflect just indicated is sometimes referred to as the pontine flexure (see the Chick). Beside the thickenings caused by the fiber tracts there is also at deeper levels the development of numerous neurones connected with the cranial nerves which arise from the sides of this part of the brain. The lumen of the metencephalon remains fairly large, and is considered a part of the fourth ventricle. Posterior to the metencephalon the myelencephalon becomesa tube which tapers off into the spinal cord, and is designated as the medulla. In most respects the medulla resembles the cord except that it is wider, especially anteriorly, and its extensive roof consists of a thin membrane into which blood capillaries soon press. This produces a vascular ‘infolding similar to that described in connection with the diencephalon, and in this case termed the posterior choroid plexus. The broad shallow cavity of this region into which these folds push is also quite extensive, and constitutes the larger part of the fourth ventricle. The ventralateral walls of the medulla are essentially similar to what has already been described with respect to the walls of the neural tube. They consist internally of a lining of ependymal cells, a middle mantle layer of neuroblasts which become nerve cells, and an outer marginal layer of iibers. It may be further noted that dissection, or cross sections, show that a groove runs along either side of the internal wall of this region, termed the sulcus limitans, dividing it into a dorsal and ventral part.

The Neural Tube

When last noted at 10 mm. the essential layers and types of cells in the tube were already beginning to differentiate. Further development consists mainly in the continued production and difierentiation of these cells, so that the cord not only becomes larger, but assumes its characteristic shape. Thus in cross section we find the ependymal cells lining the now relatively small central canal, and sending their supporting processes transversely through the substance of the cord. Within the mantle layer the spongioblasts ultimately all become supporting cells of other types, while the neuroblasts all finally become transformed into nerve cells. As a result of growth this layer finally assumes in cross section a somewhat butterfly shape (i.e., with wings extended), constituting the so-called gray matter of the cord. The dorsal andrventral extensions (horns) of the “ butterfly wings ” serve to divide the outer marginal layer into four tracts of relatively white material. These tracts or columns consist of bundles of medulated fibers, the myelin substance in the fiber sheaves giving the tracts their white appearance. The dorsal column consists mainly of sensory fibers conducting impulses to the brain, while the two lateral columns and the ventral column are motor paths from the brain to the various spinal nerves.

The Cranial Nerves

The origins of all cranial nerves, save the I and II, have already been indicated, and there is little more that need be said about them except to note briefly the parts which they ultimately innervate in the Pig. In general the relationships of nerves and parts are the same as in the Chick in so far as comparablestructures exist. Thus the III or oculamotor nerve as usual supplies the inferior oblique, and the superior, inferior and internal (anterior) rectus muscles of the eye. The IV or trochlear nerve innervates the superior oblique eye muscle, while the external (posterior) eye muscle is innervated by the VI or abducens nerve. Passing to the most anterior of the mixed neigves we find that the ophthalmic branch of the V or trigeminal nerve comes to supply the snout, eyeball, and upper eyelid; the maxillary branch supplies the upper lip, jaw, palate, face and lower eyelid; the mandibular branch supplies the tongue, lips, muscles of the jaw, the lower jaw itself, and the external ear. The VII or facial’ nerve was but slightly developed at 10 mm. As its name suggests, it supplies the face, and is primarily motor, though the existence upon it of the geniculate ganglion shows that it contains some sensory fibers. These fibers come eventually to join the mandibular branch of the V nerve and evidence indicates that they concern the sense of tiiste. The VIII is of course" the auditory nerve, and is ‘entirely sensory, being concerned with both hearing and the sense of equilibrium. Though at first closely associated with the VII its ganglion later becomes more distinct, and eventually divides into two parts the vestibular ganglion and the spiral ganglion. The branch from the former supplies the semicircular canals, is termed the vestibular nerve, and is concerned with equilibrium. The cochlear nerve from the spiral ganglion innervates the cochlea, and is concerned with hearing. The IX or glossopharyngeal nerve fibers are mainly sensory, and come to sup-V ply the pharynx and tongue. Such motor fibers as there are pass to the pharynx. The X or vagus nerve develops further as follows: Sensory fibers from the ganglion jugulare come to innervate the external ear, while sensory fibers from the ganglion nodosum eventually reach the pharynx, larynx, trachea, esophagus and thoracic and ‘abdominal viscera. Motor fibers of the X nerve innervate the pharynx and larynx, while other motor fibers connect with the sympathetic ganglia, and supply the visceral musculature. The XI or spinal accessory nerve, as previously noted, loses Froriep’s ganglion (which disappears), and thus this nerve becomes entirely motor, and its fibers are very closely associated with the motor fibers of the vagus. Many of them also run to sympathetic ganglia, and thence to the viscera. Other motor fibers of this nerve help to. innervate the pharynx and larynx, while still others originating along the cervical region of the cord proceed to the trapezius and sterno-cleido-mastoid inuscles. The XII or hypoglossal nerve is the motor nerve oflthe tongue. The muscles which it innervates originate further back and migrate anteriorly as the tongue develops, carrying the branches of the XII nerve along with them. Indeed phylogenetically the tongue muscles are probably derived from the occipital myotomes, and the XII nerve was -originally a spinal nerve which has recently become cranial. '

The origin and development of the I and II cranial nerves will be taken up in connection with the organs of special sense along with which they develop.

Spinal Nerves

The Somatic Nerves

As regards the further development of the somatic spinal nerves, it may be said that their afierent and efferent fibers grow until they come in contact respectively with skin or muscle. Then as the latter parts develop and move further away the. fibers grow so as to maintain their contact. The sheaths of these fibers have two.

sources. The neurilemma is formed of cells of ectodemial origin which accompany the fibers as they grow out. The myelin sheath. on the other hand is not itself cellular; but is a cell product which accumulates at numerous points between the neurilemma and the nerve fibers. These accumulations then spread until they meet, the meeting points forming the nodes of Ranvier.

The Autonomic Nerves

The origins of the autonomic nervous system have already been stated, and the fact that it involves both parasympathetic and sympathetic parts. Each part of course has to do with controlling the involuntary movements of the viscera, and as in the case of the somatic nerves, when the fibers make contact with the organs which they are to innervate they grow with them. It is of interest that the two parts of the system largely overlap with respect to the structures which they reach, and that they have opposing functions. Thus the symp_athetic fibers reaching the heart from certain postganglionic neurones carry accelerating nerve impulses. On the other hand, impulses in the parasympathetic fibers from the brain via the vagus nerve to postganglionic neurones on the organ itself, have a retarding influence.

The Organs of Special Sense

The Olfactory Organ and I Nerve

Following the formation of the olfactory pits, and the establishment posteriorly of their communications with the oral cavity, the further development of the olfactory organs proceeds as follows: In the lateral walls of each nasal chamber folds develop known as conchae or nasaturbinals, these folds being more numerous in many lower animals and in the human fetus than in the human adult. Meanwhile the epithelium, at first simple cuboidal, soon becomes more or less stratified columnar throughout a large part of its extent, with the occurrence of many ciliated and goblet cells. On the more dorsal conchae, and on the median septum formed by the fusion of the naso-median processes, however, the original cuboidal epithelium becomes transformed into that of the specifically olfactory type. In these regions no goblet cells are formed, and the tall columnar cells which develop here lack cilia.‘Also just beneath the surface certain of the cells turn out _to be neuroblastic. From each of these a fine bristle-like process projects through the epithelium to the surface. At the same time from its opposite pole each of these cells sends an axone to the olfactory bulb or lobe of the brain. The bundle of axones from each of the two olfactory areas then come to constitute the I or olfactory nerves’. Eventually the various nasal sinuses, i.e., the ethmoid, maxillary and frontal are developed by the invasion of the bone by the non-olfactorys nasal mucosa which gradually excavates the bone substance, and then lines the spaces so formed. The further development of the posterior nasal passages and the internal nares will be referred to in connection with the account of the oral cavity.

The Eye and Optic Nerve

Except for one feature the development of this important organ is essentially the same in the Mammal as in the Bird, where it was described in some detail. The vascular pecten, presumably an organ aiding in the nutrition of the inner parts of the Bird eye, does not exist in the eye of the Mammal. There are, however, blood vessels of course which supply the mammalian retina and lens. These are capillaries arising from a branch of the ophthalmic artery. This branch enters the optic cup along the groove on the ventral side of the optic stalk by way of the proximal part of the choroid fissure. It is atfirst called the Ityaloid artery because it supplies only the developing lens, but later it supplies the retina also, and is then called the central artery of the retina. Shortly after it appears, axones from the cells of the neuroblasts (future ganglionic) layer of the retina start growing back along the artery which they soon come to surround. As the number of these fibers increases they encroach on the tissue of the original stalk. Finally they become medullated and surrounded by a connective tissue sheath, while the old stalk cells are virtually eliminated. Thus are produced the I or optic nerves. As is well known, in the case of the mammalian eye the fibers from the median sides of the two retinas cross in the optic chiasma, while those from the lateral sides do not.

As suggested the development of the eye proper, aside from the points noted, is so similar to that of the Chick that no further comment on it is deemed necessary.

The Auditory Organ

The Membranous Labyrinth

In the 10mm. Pig the only indication of the auditory organ was the occurrence of the usual otic vesicle with its upgrowing endolymphatic duct. It now remains to state that from this vesicle the membranous labyrinth of the inner ear develops essentially as in the Bird, except that 'n the Mammal one feature of it develops considerably further. Thus it wi 1 be recalled that in the former case the semicircular canals arise from the upper part of the otocyst termed the utricle. Then the lower portion of the otocyst partly con- _ stricts away, and produces an outpocketing called the sacculus. Up to this point the situations in the Bird and Mammal are similar. In the Bird, however, it will be remembered that the larger part of the ventral portion of the otocyst is not involved in the sacculus, but grows out into a relatively short tube termed the lagena. In the Mammal these same parts exist, but here'the whole “ lagena ” is called the ductus cochlearis or cochlear duct, and its connection to the utricle becomes narrowed to a slender tube, the ductw -reuniens. Furthermore the remainder of the mammalian ductus cochlearis continue: to grow until it has produced an extensive spiral tube on whose floor the cells eventually become re. arranged and differentiated to form the organ of Corti, and the tectorial membrane. These last named structures, the most elaborate parts of the organ of hearing, have no counterpart in the Bird. This, it may be suggested, is a somewhat remarkable fact in view of the auditory stimuli which some members of this latter group can produce, and hence presumably appreciate. Surely the song of the Nightingale should require a more complicated organ of reception than the Pigs grunt! Finally it remains to state that, as in the Chick, the whole membranous structure derived from ectoderm is closely covered by a mesenchymal layer, the membrana propria (Fig. 327).


Fig. 327.--A,'B, C and D, stages in the development of the membranous labyrinth of the Human ear. After Sireeten Although this is the Human ear and not that of the Pig, the latter is presumably very similar, as are those of all Mammals so far as known. All views are of the left ear from the left, i.e., lateral, side. A. The otic vesicle from a 6.6 mm. embryo, showing rudiments of the membranous semicircular canals» starting to form, also the beginning of the endolymphatic duct. B. Membranous labyrinth from a 13 mm. embryo. C. Membranous labyrinth from a 20 mm. embryo. D. Membranous labyrinth from a 30 mm. embryo. E. A semidiagrammatic representation of the middle and inner ear opened from the side. Modified from various sources. F. A diagrammatic section through one side of the cochlea, including of course the scala tympani kind vestibuli and the cochlear duct, showing the organ of Corti.


The Bony Labyrinth

Again as in the Bird, there has been developed around the membranous labyrinth and its mesenchymal membrana propria a bony labyrinth, the two labyrinths being separated by the perilymphatic space. Naturally, however, in this case the bony capsule or labyrinth has also to be more elaborately formed in order to encase the spiral ductus cochlearis. Not only does it also become spiral in order thus to encase this region, but in doing so it becomes divided into two channels. One, dorsal to the ductus cochlearis, is the scala vestibuli, while the other ventral to it is the scala tympani. At the apex of the spiral, at the end of the ductus cochlearis these channels communicate. At the other end surrounding the sacculus and the utricle the wall of the scala vestibuli contains the fenestra ovalis to whose membranous covering is attached a bone of the middle ear. The wall of the scala tympani in this region contains the fenestra rotunda also covered by a membrane.

The Middle Ear

Considering next the middle car we find again the same parts involved as in the Chick, but once more with a slightly diffierent outcome in certain respects. The first or hyomandibular pouch grows out-until it makes contact with the ventral part of the corresponding visceral furrow. This initial contact, however, does not long continue. The upper part of the pouch enlarges, but at the same time withdraws somewhat from the ectoderm of the furrow, while between them mesenchyme develops. Presently within this mesenchyme cartilaginous concentrations arise, representing the developing ear bones or ossicles. In this case, however, instead of there finally developing only one such bone, the columella, three of them appear— the malleus, incus and stapes ( Fig. .327). At the same time that the cartilaginous anlagen are becoming ossified to form these bones, the mesenchyme surrounding them is being absorbed. As this occurs, the upper end of the visceral pouch once more extends so that it surrounds the developing ossicles, including a little of the disappearing mesenchyme. It also again almost reaches the outer ectoderrn, being separated from it only by a thin sheet of mesenchyme. Thus there is formed the permanent cavity of the middle ear, or tympanic cavity. The part of the visceral pouch between this cavity and the pharynx remains, of course, as the Eustachian tube. It thus also comes about that the tym panic membrane or tympanum consists, as in previous cases, of tissue derived from each of the germ layers, the outer lining being ectodermal, the middle layer mesodermal, and the inner lining endodermal. On its median side the lining of the tympanic cavity is in contact with the bony capsule of the inner ear, and so forms a membrane over each of its two fenestra. To the membrane covering one of these, the fenestra ovalis, the stapes is attached, while at the other end of the bony chain the malleus of course is fastened to the tympanum. Though most of the mesenchyme about the ear bones is ultimately absorbed, some of it becomes dilferentiated into the small muscles attaching the ossicles to the wall of the tympanic cavity. It is also interesting to note that in Man this mesenchyme does not entirely disappear until a few months after birth. This apparently serves to prevent free movement of the ossicles, and thus to protect the ear of the infant from too strong stimulus by loud noises.

Homologies

Turning now to the possible homologies of the mammalian ear bones, it will be well to recall the situations which were described in the Frog and Chick. Thus in the former animal, though only one bone, the columella, finally existed as a separate entity within the completed middle ear, there were originally two elements concerned. For, fused to the inner end of the columella, there was also the operculum, lying within the fenestra ovalis. At its outer end, moreover, the columella connected with a ring of cartilage around the tympanic membrane called the annulus tympanicus. In the Chick there was again a columella which fused with an opercular element, in that case called the stapes, but the -annulus tympanicus was lacking. In these cases it was suggested that the columella was possibly the homologue of the hyomandibular element ofthe hyoid arch of the primitive fishes, and that the annulus tympanicus might be the homologue of the pa1atoquadrate cartilage of such forms. In the Mammal, where there are three separate ossicles, the question of possible homologies again arises. It has been suggested that the mammalian stapes corresponds to the columella, and hence ultimately to the hyornandibular, the incus to the palato-quadrate (primitive upper jaw) and the malleus to Meckel’s cartilage (primitive lower jaw). This obviously leaves the opercular element of the Frog and the stapes of the Chick quite out of the picture. As stated in connection with the Frog, there is good evidence, experimental and otherwise, to support these suggested homologies, and they are, therefore, quite generally accepted. Thus the intriguing notion that parts once connected with the coarse work of seizing food have finally been promoted to the delicate “ white collar ” task of transmitting sound waves, seems to be well established. It probably affords an example of functional adaptation correlated with a changing environment.

The Digestive and Respiratory Systems

The Oral Cavity

Originally the anlage of the oral cavity existed merely as the stomodaeum, a relatively shallow pocket lined with ectoderm. By the 10 mm. stage, the oral plate which constituted the stomodaeal union with the fore-gut had broken through, and the roof of the stomodaeal cavity had given rise to Rathke’s pocket. Subsequent to 10 mm. the stomodaeum becomes greatly deepened to form the actual oral cavity, while Rathke’s pocket becomes separated from it, and as already noted, gives rise to the anterior part of the pituitary. The deepening of the cavity as just suggested is extensive; so much so in fact, that eventually we find the tonsils occurring "at about the original site of the oral plate. This enlargement is brought about chiefly by the outgrowth of the mandible, and the various processes giving rise to the face, nose and upper jaws. The external aspects of this procedure have already been described, but it remains to indicate some of the details more especially concerned with the mouth itself. Thus it will be recalled that the maxillary processes formed the sides of the upper jaw (maxillae) , while the anterior tip was derived from the fused naso-medial processes. This tip is the premaxillaryt region, and from it there grows backward a small median plate constituting the more anterior portion of the palate, and termed the median palatine process (Fig. 328). By far the larger part of the permanent roof of the mouth, however, is formed by the two lateral plates, the lateral palatine processes. These are simply median extensions of the maxillary processes which soon meet and fuse in the middle line. The more posterior plate so formed then unites with the median palatine process and thus together these parts constitute the complete hard palate. It is now to be recalled that ‘the temporary internal nares open into the oral cavity through its original roof fairly near the front.,The formation of this new roof beneath the first one, however, creates a new chamber between the two roofs into which the nares open.


Fig. 328.——Illustrations to show the development of the roof of the mouth and the nares of the Pig. A and B. The roofs of the mouths of specimens of the sizes indicated, the lower jaw having been removed. C and D. Transverse sections of the snouts of the same specimens at the levels indicated by the lines at each side of A and of B. E. A transverse” section, made with a microtome, of a snout of a somewhat older embryo than D at about the same level. This section appears somewhat smaller than D because it does not show the surrounding parts of the head, and because it was apparent1y.somewhat compressed laterally in cutting.

The further development of the nasal septum to fuse with the new or 1 lower roof then divides this chamber into two lateral parts. In this way ' there is produced essentially a posterior extension of the nasal cavities so that the definitive internal nares eventually open well back toward the throat.




Fig. 329.—-A. Transverse section through the right side of the lower jaw and tongue of a Pig embryo somewhat older than the oldest in Fig. 328, showing the beginning of tooth development. BThe same section shown in A, but at a much lower magnification soas to show the whole jaw, with an indication of the part from which A was taken. Connection of enamel organ with dental ledge has gone.


While this is going on in the roof of the month, the tongue is being formed in the-floor. As in the Chick it is made up of three thickenings, a median one called the tuberculum impar, and a pair of lateral ones. These lateral primordia soon overgrow the median one to form a single mass which for a time lies between the lateral palatine processes. As these come together, however, the tongue drops down to its adult posi tion (Fig. 328).


Finally by the 23-30 mm. stage a thickening of the oral epithelium (ectoderm) has developed around the border of both jaws. This thickening, termed the labio-clental ledge or lamina, pushes into the underlying mesenchyrne, and presently its inner and outer edges become particularly developed. The outer edge or part is called the labia-gingival lamina (later a groove), and serves to separate the lip from the inner part of the originally single thickening (Fig. 329). This inner part is called the dental ledge or lamina, and within it the teeth eventually develop. Since these latter structures do not occur at all in modern Birds, and were not mentioned in the Frog where they are not highly evolved, we shall consider their formation separately along with that peculiarly mammalian product, hair. _

The Pharynx

The pharynx begins at approximately the line where the oral plate disappears, and thus is the most anterior part of the alimentary and respiratory tracts to be lined by endoderm. It is also the part which is flanked laterally by the remains of the visceral arches posterior to the mandibular, and by the pouches. These arches and pouches very shortly disappear as such, but as will be apparent, their remains give rise to Various adult structures as follows:

Thus the second or hyoid pair definitely produce the styloid processes and lesser horns of the hyoid. There is also the possibility, as noted, that the columella (mammalian stapes) of the car may be derived from it. The third pair of arches give rise to the greater horns of the hyoid, while from the fourth pair of arches is derived the thyroid cartilage of the larynx. No distinct fifth arches are ever visible, in the Pig, but from the region where they should lie come the cricoicl and arytenoid cartilages. All of these parts are of course involved in the formation of the larynx, and immediately adjacent structures.

Turning to the products of the visceral pouches we find that, as we have already noted, the first or hyomandibular pouches take part in the formation of the Eustachian tubes and tympanic cavities. The second pair in connection with ingrowths of lymphoidtissue produce the main or palatine tonsils. The third pair give rise to the main or definitive thymus bodies (thymus III), which migrate posteriorly until they are eventually located in the upper part -of the thorax. It is interesting to note that in the Guinea Pig the thymus bodies are permanently in the neck instead of the thorax. This is apparently because the third pouches in this case are so firmly fused to the ectoderm that they cannot be carried backward (Klapper, ’46). In addition to becoming transformed into thymus tissue this third pouches also produce outgrowths which become the chief pair of parathyroids (parathyroid III). These are located in the neck where they are ultimately associated closely with the posterior parts of the thyroid. With respect to the fourth pair of visceral pouch derivatives there has been some disagreement. So far as the Pig is concerned Godwin ( ’4~0) concludes that, as noted, this pair of pouches are not always present. When they are, he thinks that the remains of the pouches proper become incipient thymus bodies (thymus IV) which later disappear. In addition there are produced in this animal two distinct outgrowths either from the pouches if they are present, or if they


Fig. 330.—The pharyngeal region of a 10 mm. Pig embryo, showing diagrammatically the regions iroin which the thyroid, thymus and parathyroid bodies either have been, or will be, derived. are not, from the region of the pharynx where they would be. One of these outgrowths is an additional pair of parathyroids (parathyroid IV), each of which, according to ‘Godwin, soon divides into two parts which persist. Others, however, have claimed that they disappear. The other outgrowths are the pair of post-branchial bodies. Each of these bodies eventually becomes embedded in the thyroid gland. According to Godwin, however, there is nothing to indicate that they ever become actual thyroid tissue as believed by some (Fig. 330).

The thyroid gland as in other forms arises as an evagination from the floor of the pharynx between the first and second visceral pouches. It soon loses its connection with the pharyngeal floor and becomes almost, though not quite, completely divided into two lobes (Fig. 296). These lobes then migrate posteriorly somewhat to lie eventually at the base of the neck. As noted the parathyroids are closely associated with the thyroid, and the ultimo-branchial body becomes imbedded in it, whether a part of it or not. Though the thyroid becomes separated from its point of origin this point at the future root of the tongue“ is marked, in Man





Fig. 331.—A, .C and E are semi-diagrammatic representations of the developing stomach and mesenteries of the Pig, as viewed from the ventral side. The dash lines in C and E represent the part of the mesogastrium on the dorsal side which is‘ covered by the stomach in this view. The liver and ventral mesenteries (gastro hepatic otnentum and falciform ligament) are not shown in these figures as they would obscure the stomach. B, D and F are diagrams of transverse sections through A, C and E viewed from the anterior. G is a diagram of a transverse section of liver, stomach and colon in Man at a later stage when the stomach and colon have become transverse to the body. Hence this section is mid-sagittal for the body as a whole The great ofnenturn, which does not occur in the Pig, is obviously an extension of the fall}. of the original dorsal mesentery down across the anterior (ventral)

wall of the abdomen. It,is largely this fold which accumulates fat in older persons.

THE ESOPHAGUS 627

at least, by a permanent depression, the foramen caecum. The histological differentiation of the thyroid is fairly simple. The endodermal derivatives become broken up into nests of cells which form the secreting follicles, surrounded by mesodermal connective tissue ‘and blood capillaries.

One other structure of the pharynx remains to he mentioned, the epiglottis. It arises as a thickening in the floor of the pharynx just posterior


esophagus



Fig. 332.— Stages in the development of the intestine of the Pig from the gut loop stage to that in a 35 mm. embryo. After Linehack.

to the lower ends of the third pair of visceral arches. It grows posteriorly, and eventually overhangs the slit-like opening to the larynx, i.e., the glottis.

The Esophagus.—At the back of the pharynx the original gut canal had become separated at 10 mm. into a dorsal and ventral division, and the latter was starting to become differentiated into the respiratory system. The dorsal part, on the other hand, was already becoming narrowed to constitute the esophagus. In carrying on the description of these parts it will be convenient to discuss the digestive portion of the originally undivided gut separately from its respiratory derivatives. In so doing we shall consider the former first.


The esophageal part of the digestive tract posterior to the pharynx is, as previously indicated, already relatively constricted. Its inner endodermal lining becomes differentiated into a smooth non-ciliated epithelial layer, and into mucous glands which extend into the connective tissue (submucosa) beneath the epithelium. The connective tissue and muscular coats are of course derived from»-mesoderm. ~

The Stomach and Its Mesenteries. — At 10 mm. the stomach was represented by an enlargement in the primitive gut posterior to the esophagus. As elsewhere this part of the gut was attached to the dorsal body wall by its dorsal mesentery (dorsal mesogastrium). This enlarged region is already slightly bent with the convex side dorsal, and very shortly three things happen to it. (1) The bend increases, (2) the anterior end shifts to the left, and (3) the whole structure rotates on its longitudinal axis in a clockwise direction when viewed from the esophageal end. As these movements take place it is obvious that some adjustment must be made by the attached mesenteries. What occurs is that the dorsal mesogastrium is extended to accommodate the bending and rotation of the stomach. Furthermore, since the line of attachment of mesentery to stomach does not change as the stomach rotates, ‘this line necessarily rotates with it. Thus in the new position the line of mesenteric attachment simply follows the curve around the left convex side of the organ. As these changes occur with respect to the dorsal mesentery, the ventral mesentery has likewise had to shift its position so that it now leaves the stomach on the concave side of the latter (Fig. 331).



Fig. 333. —A continuation of the development of the Pig intestine shown in Fig. 332 with special reference to the region of the colon. After Lineback. .


In connection with these alterations certain further facts need now to be noted as foliows. We have seen how, as the stomach changes its position, the dorsal and ventral mesenteries change to accommodate it. In the course of this accommodation it is clear that the dorsal mesentery must increase in extent. It remains to add, however, that this mesontery increases more than would be required by the shift of the stomach. As a result a fold of the mesentery comes to extend out beyond the stomach so as to form a sort of wide pocket. This fold and pocket are called the omental bursa, the spleen later developing within the walls of the fold. Inspection of Figure 331 will show that an opening from the general coelom into this more restricted pocket area occurs from one side. This opening, at first quite wide, becomes much narrowed later on, and is known as the epiploic foramen. In Man the fold itself also develops further to form still another structure which will be noted in connection with the development of the intestine.

The Intestine

The intestine at 10 mm. consisted anteriorly of a short region to which the liver and pancreas were attached, the duodenum, followed by a loop whose limbs passed into and out of the umbilical stalk. At the ventral apex of this loop a very narrow tube still represented the yolk-stalk, while the upper end of the posterior limb bent around caudally to the rectum (Fig. 332, 12 mm.). The whole structure was of course supported by a mesentery. By the 24« mm. stage the anterior limb of the former simple loop has become very markedly coiled, and it is this region which forms the main part of the small intestine. Upon the posterior limb of the loop a short distance from the apex, a slight outpocketing or caecum was evident at 10 mm., and shortly thereafter it becomes a distinct diverticulum (Fig. 332, 24 mm.) . In Man this caecum gives rise to a finger-like extension, the vermiform appendix. From the point where the caecum grows out the distal part of the original posterior loop becomes the large intestine or colon. Eventually this part bends so that the small intestine enters it at a right angle. Also it too becomes coiled, forming a loop, a condition not found in Man (Fig. 333). In correlation with all this bending and coiling the dorsal mesentery of these parts of the intestine also becomes thrown into somewhat involved configurations which it is not necessary to go into. It is of interest, however, to note a further development of the mesentery in the region of the stomach which occurs in the case of Man, but not in the Pig. It occurs as follows:

The fold of the bursa, as previously described for the Pig continues subsequently to increase in extent in the human embryo, and to grow caudad, until eventually it comes into contact with the‘ parts of the colon occupying a transverse position in Man. When this condition is reached the bursal fold fuses with theepaetitczmeal covering of the colon, and later, after birth, continues ‘to grocsw still further in a caudal direction. At the same time the two liimlitsctftltie fold beyond the line of fusion with the colon unite with ome antotlzflier no form a double sheet. This sheet, the great omenlum, thus co-nstiitutmesa. sort of apron covering the lower abdominal viscera on their veentrz-3 al( anterior) side between them and the ventral body wall (Fig. 3311]." This is possible because in this region the ventral mesentery haslnng‘; sithnce disappeared. Later this part of the omentum usually becoxrnesastoontgeptt lace for fat, a feature which is frequently all too obvious in caldeerirz:-en .and women.

The Recturn.—At the 1(1) Ir::-.1111. stage the cloaca, into which the large intestine opens, vtras in garoczess of being divided by the urorectal fold to form the rectum arid tjhe urimogenital sinus. The cloacal membrane also had not yet rutptumerl I. Tlte completion of these processes, however, is more readilydescr"ihoo din. connection with the description of the development of the exte» rnulg<=_=2nitalia. and related parts. It will therefore be deferred until that subojeci-tis discussed.

The Liver and Its Mesenteries

We are now prepared to return to the develop‘me1:1‘o‘E th:-istx_)utg:roWth of the duodenum. It will be recalled that in the Pig th_ere is only one hepatic diverticulum insteadof two. This single outgr owtth 0 (ductus choledochus), moreover, had produced several anter iorl ytllireoctecl buds, the anlagen of the liver tubules, while the remainso ftlneo outgrowth was extending posteriorly as the anlage of the cystic duct zantllgall bladder (Fig. 307). This anlage rapidly elongates to form theieefiuiiive duct while its end. enlarges to produce a bladder. Me anwhiloethaeamteriorly directed tubules grow out into the ventral mesentery’ wlr:1ete-ethey soon come into contact with the Vll"‘lliI16 (oniphalozmesenteric ]v-veins; into which they push. They thus break these vessels up in to finnr umeerable sinusoidal capillaries which ramify amongst the liv’ert:uh1..t1les.a.ln this manner the tubules and capil laries come .to constitute the manin mass of the hepatic substance with only a relatively small arnountttcif supporting connective tissue. Having completed our description of ties dervelopment of the organ itself it remains to say a few words zregs arrli ing its mesenteries.

It has been repeatécllyslatecdthliat the liver develops within the ventral mesentery of the Stomach ancfiitnodeanum. It may now be ‘added that the part of this mesentery which .at ztachnes the hepatic mass to the intestine and stomach is known as the: lesaser orrrentum, or sometimes the gastrohepatic omentum (gastro—lie1::patio cligarnent in the Chick). Beneath the liver, i.e., between it amdtzlto ' van-ntral body wall, a small portion of mesentery also permanently persists in the Mammal, where it is termed the falciform ligament, connecting liver and body wall. This ligament is absent in the Bird as previously noted (Figs; 331, 335).

The Pancreas

Even as the liver in the Pig has only one origin instead of two, so the Pig pancreas has only two origins instead of three. The two primordia in question were already in evidence at 10 mm. One consisted of an outgrowth from the dorsal side of the intestine of a mass


Fig. 334.—-Later development of ‘the dorsal and ventral pancreas. Slightly modified from Thyng.

of cords at a level slightly caudad to the origin of the ductus choledochus. The other arose from the ventro-lateral side of the duct itself (Fig. 307). The two growing masses soon fuse, and the cords of which they consist become tubular. These in turn produce numerous buds which develop into one of two things. Part of the buds remain connected with the tubules, and form the pancreatic acini which produce digestive secretions. The remaining buds become segregated, and constitute among the tubules little aggregations of highly vascularized tissue, the islets of Langerhans. Although the pancreas in the Pig has two origins as indicated, the adult organ has only one duct. This is derived from the dorsal outgrowth, and hence connects directly with the duodenum. The ventral connection with the ductus choledochus in this case disappears (Fig. 334).

It is of interest to note at this point that in the Mammals generally this double, rather than triple, origin of the pancreas is the common procedure. Whether one or both primordia are to persist as ducts, however, and if only one, which one, varies in different animals. Thus in the Horse and Dog there are two permanent pancreatic ducts. In the Sheep and Man on the other hand there is only one, and in these cases the ventral one opening into the base of the common bile duct. In the Ox, and in the Pig (as already indicated), however, the dorsal duct is the persistent one, opening as noted into the duodenum.

Lastly, it should be recalled that as the liver outgrowths occur into the ventral mesentery, so the pancreatic outgrowths push into the dorsal mesentery. Furthermore, though they start into this mesentery at the level of the duodenum, the fused pancreatic elements soon extend anteriorly into that part of the mesenterylsupporting the stomach, i.e., the rnesogastrium. Then later as this forms the omental bursa we find the pancreas in the more dorsal limb of the bursal fold, which eventually becomes adherent to the dorsal wall of the coelom (Fig. 331).

The Respiratory System

The cartilages of the larynx have already been noted in connection with the fate of the visceral arches. Also the initial development of the trachea and bronchial outgrowths were indicated as present at 10 mm. Following this period the main bronchial tubes and their branches continue to push out into the coelomic spaces (pleural cavities) beneath the esophagus and above the heart‘( Fig. 303). The lining of the tubules is columnar or cuboidal, but at their terminals the tubules produce little sacs, the lung alveoli, and here the epithelium becomes thin and flat.

It must now be pointed out that when these endodermal outgrowths first occur they do not really lie in the pleural cavities. Rather they lie in a thick sheet of mesoderm which hangs from the dorsal body wall like a rnesentery, and which, in addition to the trachea and lung buds, also contains the esophagus. It is the dorsal part of the mediastinum. Though within this structure at the start, the branching bronchi, as indicated, soon push out of it into the antero-lateral extensions of the coelom termed the pleural canals or cavities. As they do so they carry, reflected over them, a layer of mesoderm. This produces the mesothelium of the visceral pleura, the connective tissue about the alveoli and bronchi, and the cartilaginous rings of the bronchi.‘ At the roots of the lungs the mésothelium is of course reflected laterally onto the outer wall of each pleural canal to form the parietal pleura. Finally it remains to note that the pleural (coelomic) spaces within which the lungs lie are not at first separated posteriorly from the rest of the coelom. This and the completion of the pericardium comes about in a manner which will now be described.


1 It has been claimed (Clements, '38) that the endoderrnal epithelium of the alveoli in the Pig (and probably other Mammals) later disappears entirely, leaving the blood capillaries covered only by a very thin sheet of connective tissue. ~c,.a_..


Fig. 335. ——Diagrams to illustrate the separation of the pleural, pericardial and abdominal cavities, and the formation of the diaphragm in the Pig and other Mammals. A. Transverse section of the body just behind the septum transversum. B. Transverse section of the body through the lung region. C. Lateral view of median region showing forming septa in relation to heart, liver, lungs and gut.

Completion Of The Division Of The Body Cavity

The Diaphragm. ——The development of the pericardium and diaphragm has already been described somewhat in the case of the Bird where, however, the strictly diaphragmal parts are incompletely formed. Also the structures involved are somewhat different in their origin. We shall therefore start from the beginning in the Pig.

The first part of the diaphragm to appear is the septum transversum. In this case it consists of a layer of tissue growing dorsad from the ventral body wall just anterior to the liver to whose face the septum is fused. The median part of this septum also forms the posterior wall of the pericardial cavity, i.e., the part of the parietal pericardium separating the cavity from the coelom posterior to it. The sides of the septum, however, form the ventro-lateral parts of the diaphragm separating the ventral portions of the pleural cavities from the coelom posterior to them. The dorso-lateral parts of the diaphragm completing this separation are formed by a pair of membranes, the pleura-peritoneal folds, growing out from the body walls-(Fig. 335, A). In the middle they meet the dorsal mediastinum and complete the diaphragm. These folds also extend anteriorly in such a way as to bound the pleural cavities (canals) ventrally and the pericardial cavity dorsally. The ventral and caudal growth of the lungs then occurs, causing these organs to lie more on either side of the heart than above it. As this takes place the lungs split off more and more of the pleural-peritoneal folds from the body walls, and push these augmented folds before them._As this occurs

on the median side next to the heart, the folds come to constitute the _

lateral and ventral as well as the dorsal pericardial wall, and likewise the medial pleural walls. Hence these parts of the pleural-peritoneal folds (septum) are called the pleura-pericardial septum (Fig. 335, B, C ) .

The posterior pericardial wall formed by the median part of the septum transversum has already been noted. Anteriorly where the vessels of the heart emerge, the parts of the parietal pericardium come together, and are reflected over the heart muscle as the visceral pericardium. Here also these parts fuse to form the dorsal mesocardium, attached to what was the ventral edge of the dorsal part of the mediastinum. It is to be noted, however, that though the pleuro-pericardial folds meet and fuse ventrally, the pleural cavities never become coextensive. Hence the ventral wall of the parietal pericardium is attached to the ventral body wall. Thus the pericardium and heart now form a central mass connecting the former ventral edge of the dorsal part of the mediastinum with the body wall. This mass might then be referred to as the ventral part of the mediastinum. Actually because of shifts dur ing development the various parts of the mediastinum are difierently named, but the details of this need not be gone into here.

The Circulatory System

When this system was previously discussed we began with a description of the blood islands, and followed with the development of the heart, leaving the intra-embryonic blood vessels until last. Nothing further need be said of course about the blood islands which soon disappear, and for various reasons it is more convenient to begin with the blood vessels rather than the heart. We shall therefore start with the arteries.

The Arteries

The Aortic Arches and Related Vessels. -—It will be recalled that at 10 mm. the first pair of aortic arches had disappeared, while the third, fourth and sixth remained, the fifth being vestigial. From the base of the third pair the external carotids were just beginning to develop, while the sixth pair had produced rudimentary pulmonary arteries. Dorsally the arches on each side were still connected by the dorsal» aortae which continued anteriorly as the internal carotids. Posteriorly the aortae had fused as far forward as the anterior appendages, and posteriorly to the tail.

Subsequent to 10 mm. we find that the base of each third arch between the origin of the respective external carotid and the point of origin of the fourth arch becomes lengthened somewhat. These lengthened bases thus come to constitute the two common carotids (Fig. 317, B, C). Conti.r..1ing posteriorly the part of each dorsal vessel between the third

and fourth arches as usual disappears, while on the left side the fourth arch and the dorsal aorta posterior to it enlarge and persist as the main or great aortic arch of the adult (Fig. 319, B). At this point two important differences between Bird and Mammal are to be noted. One of course is the fact that in the former it was the right arch which so persisted. A second difference is that whereas in the Bird the fourth arch opposite the great aorta entirely disappeared, in the Mammal it does not. Thus in the Mammal this arch, in this case the right, remains to form two things. Its proximal part constitutes the brachioceplzalic artery (innominate) while its more distal parts, together with a portion of the right dorsal aorta, comprise the proximal part of the right subclcwian artery. The rest of the right dorsal aorta disappears. The left subclavian, it may be noted, arises directly from the distal part of what was the left dorsal aorta, but which later becomes simply a part of the main aortic arch. The genesis of the right subclavian distal to its aortic portion will be referred to presently. It now remains to add in connection with the carotids that in the Pig the left common carotid usually shifts its point of attachment so that eventually it does not arise directly from the left (main) aortic arch. Instead it emerges from the brachiocephalic close to the right common carotid (Fig. 319).


Passing now to the sixth aortic arches we are familiar with the manner in which they take part in the formation of the pulmonary arteries in the Frog and Chick. It has been indicated also that this same situation occurs at first in the Pig (Fig. 316, E). Subsequent to 10 mm., however, certain changes occur which are a little different from events in the Chick, or in other Mammals. Thus in the case of the Pig the two pulmonary branches which proceed from the upper parts of the sixth arches to the lungs, fuse with one another in their proximal regions. This single branch then retains the connection with the left sixth arch, but loses the connection with the right sixth which disappears completely. In this fashion it comes about in this animal that only the left sixth arch is involved in the permanent pulmonary circulation (Figs. 317, 319). Meanwhile there develops within the truncus arteriosus a septum dividing it into two channels. One as usual leads from the left ventricle to the systemic aorta, and the other from the right ventricle to the single pulmonary artery. In the Bird it will be recalled.that the portion of each sixth (pulmonary) aortic arch between it and the respective main aorta persists until hatching as a duct of Botallo or ductus arteriosus. In the Pig and other Mammals, however, only the left so persists. Its embryonic function and ultimate fate are similar in the Mammal to what they were in the Chick, and will be referred to again in connection with the development of the heart.

The Intersegmental Aortic Branches and Their Derivatives. —- It may he recalled that the Pig like the Chick has intersegmental arteries, and that anterior to the seventh cervical they have fused to form the vertebral and basilar arteries. It remains to note their further development as follows:

Posterior to the seventh cervical, the intersegmentals in the anterior part of the thorax also become fused antero-posteriorly, and disconnected from the aorta. Thus independent longitudinal vessels are produced in this region also (Fig. 317). Here, however, they come to supply the breasts, and are known as the mammary arteries. Returning now to the seventh cervical intersegmentals, it will be recalled that at 10 mm. these vessels have started to enlarge slightly in connection with the development of the subclavians. In fact the left one, continuing to enlarge, comes to constitute the entire left subclavian, which as noted, thus takes its permanent origin from the dorsal aorta. The right seventh cervical also enlarges, but only forms the distal part of the right sub clavian. This is l)ecause’the proximal part on this side is formed from the right fourth aortic arch, and a short portion of the right dorsal aorta THE VEINS 637

between the arch and the origin of the right seventh cervical. The part of the right dorsal aorta posterior to its junction with the seventh cervical of course disappears. Reference to figure 319 will make it clear how these developments result in the origin of both the vertebral and the mammary arteries on either side from the subclavians.

It is of some interest in connection with this origin of the subclavians to recall that in the Chick the so-called primary subclavians arise as branches of the eighteenth segmental arteries. Then a shift later occurs so that the permanent subclavians arise from the common carotids. In the Pig, as we have seen, it is the seventh cervical intersegmentals that are involved in the development of the subclavians, both originally and finally.

The Aorta and Its Branches Posterior to the I-Ieart.—The origins of the coeliac and anterior mesenteric arteries have already been noted as occurring at 10 mm. The more anterior of these, the coeliac, eventually comes to supply the stomach, liver, pancreas and spleen, while the anterior mesenteric passes mainly to the anterior and middle intestine. Posterior to the anterior mesenteric the renal arteries grew from the aorta at 10 mm. in connection with the mesonephros. Eventu ally when the metanephros develops, other arteries in close association with the original mesonephric vessels supply the new organs. The posterior or inferior m.e.senteric artery had not arisen at the 10 mm. stage, but develops at about 12 mm., and sends branches to the posterior part of the intestine at approximately the point where the latter emerges from the body-stalk. It continues to supply this part of the alimentary tract.

The largest branches of the aorta during fetal life in the Mammal are the large umbilicals whose origin has already been mentioned. It was also noted that even at 10 mm. each of them had given rise to a small branch, the external iliacs. These increase in size as the hind limbs develop, and finally at birth they become the main arteries supplying the hind legs. At the same time parts of the former umbilicals within the body, but distal to the point of origin of the external iliacs, persist as small branches, the internal iliacs. The parts of the umbilicals proximal to the external and internal iliacs remain as the common iliacs.

The Veins

Derivatives of the Omphalomesenterics. -—-"By 10 mm. the yolksac had virtually disappeared, and with it the omphalomesenteric veins leading to it. However, as was noted, the parts of these vessels within 638 THE LATER DEVELOPMENT OF THE PIG

the body proper altered to produce the hepatic portal system. This consisted of the two hepatic veins, the liver capillaries, and a single hepatic portal vein, with branches draining blood from the intestine. This is essentially the adult situation.

The Umbilical Veins. ———When last noted there were two of these within the body, though the right one was becoming smaller (Fig. 321). Presently this latter vessel disappears anteriorly, while its caudal part persists for a time as a small vein draining the body wall posteriorly into the left umbilical. The latter vein increases its size within the liver where, as noted, it forms the posterior major portion of the ductus venosus. Also, as this occurs, it comes to lie nearer the mid-line, and thus to pass between the two hepatic veins, which enter it at about the same point as the hepatic section of the developing posterior vena cava. As previously noted, the short anterior section of the ductus which empties into the sinus venosus, and was formed from the fused vitelline veins, now receives the hepatic-s, the major part of the ductus, and the hepatic portion of the posterior vena cava. Thus this short section becomes the 3'-'lt6I‘.l0I‘ extremity of that vessel. Therefore since the anterior remains of the posterior cardinals empty into the ducts of Cuvier, it comes about that the posterior vena cava is the sole vein entering the sinus from the back part of the body. The further development of the posterior parts of this important vessel will be considered presently. As to the fate of the left umbilical, its function of course ceases entirely at birth, the anterior portion of its path (the duptus venosus) being marked by a fibrous strand, the round ligament of the liver.

The Anterior Cardinal System and Anterior Vena Cava. ———- As described at 10 mm. the anterior cardinal system consisted of the anterior cardinal veins and their capillaries, and the external jugulars which joined the cardinals just anterior to the ducts of Cuvier. It was also noted that each subclavian, consisting of an enlarged intersegrnental vein, entered the posterior cardinal virtually at the point where anterior and posterior cardinals passed into the respective Cuvierian ducts (Fig. 322, E). Continuing with the subsequent story it may now be stated that with the caudal shift of the heart and ducts of Cuvier, these ‘parts soon come to lie posterior to the limb buds. As a result of this the entrance of the subclavians shifts forward so that presently they definitely empty into the anterior cardinals (Fig. 322, F).

The next steps consist in the shifting of the previously symmetrically arranged veins so that they enter the right side of the heart. This is brought about mainly by the development of a diagonally transverse vessel. This vessel runs from the junction of the left subclavian with the

left anterior cardinal, across to the right anterior cardinal, slightly pos-'

terior to the point where that vessel receives the right subclavian. In the meantime the left anterior cardinal posterior to the origin of the new vessel disappears (Fig. 322, H, I). Hence all the blood from the left anterior region, along with that from the right, now has to enter the sinus venosus through the right anterior cardinal and duct of Cuvier. With these changes the vessels concerned have their adult arrangement, and may be given their adult names. The new transverse vessel is the left innominate vein. The section of the former anterior cardinal between the junction of the left innominate with this cardinal and the entrance of the right subclavian, is now the right innominate vein (Fig. 322, I). The posterior or proximal portion of the right anterior cardinal between the entrance of the left innominate and the right duct of Cuvier, plus that duct, is now the anterior vena cava. As will presently appear both posterior cardinals have by this time disappeared as such, though certain remnants persist which will be described below. Finally the distal parts of both anterior cardinals cephalad to the points of entrance of the respective subclavians and external jugulars are now termed the int-:-rnal jugulars.

The Posterior Cardinal System, Posterior Vena Cava and Related Vessels. — It will be recalled that at about 10 mm. the posterior cardinals had practically disappeared at the mesonephric level. Their posterior remains, however, drained into the newly formed median anastomosis of the subcardinal sinuses through numerous capillaries. Anteriorly the left subcardinal had almost lost its connection with the anterior part of the left posterior cardinal‘. At the same time the right subcardinal had established a connection with the newly formed median vessel passing through the liver to the sinus venosus. This vessel, together with the subcardinal sinus and remains of the right subcardinal then constituted the anterior part of the posterior vena cava. Its establishment, as noted, has thus produced the essentials ‘of a renal portal system. The final step in this process is the complete severance of the connection of the left subcardinal vein with the posterior cardinal which occurs very shortly after the 10 mm. stage (Figs. 320, 322, C, D, E). The further development of the posterior venous system then proceeds as follows:

The posterior parts of the posterior cardinals have from an early period received the external and internal iliac veins which form in con nection with the posterior limb buds. These cardinals, however, are gradually replaced by a new pair of cardinals close to the dorsal body 640 THE LATER DEVELOPMENT OF THE PIG

wall, and hence called the supracardinals (Fig. 322, F). The external and internal iliacs then become attached to these new supracardinals (Fig. 322, F, H) through the stumps of the old posterior cardinals, now termed the common iliacs. In the region of the subcardinal sinus_ (the present end of the posterior vena cava) the supracardinals become connected, at first through capillaries, and then by larger channels, with this sinus. Just anterior to this region the supracardinals are ‘slightly developed and presently disappear, though still further forward they continue to exist and to connect with the anterior remains of the old posterior cardinals (Fig. 322, I ). We shall return to this situation presently. Continuing with the account of the more caudal region, however, we find that the final steps here are: (1) the degeneration of the left supracardinal, (2) the connection of the left common iliac with the end of the right supracardinal, and (3) the shift of the latter to the median line. The result of this is to make the surviving supracardinal the posterior extension of the posterior vena cava, thus completing that vessel in its caudal extent (Fig. 322, H, I, I) . Anteriorly the portion of it within the liver finally works its way to the dorsal surface where it becomes quite conspicuous before opening into the right atrium of the heart in a manner to be indicated presently.

Returning now to the more anterior parts of the supracardinals, and the remnants of the posterior cardinals into which they drain, we find that these vessels persist somewhat irregularly as the azygos veins. Generally the latter are united transversely, one or the other loses its anterior connection, and both drain into the anterior vena cava through the remains of a posterior cardinal, now termed the cervico thoracic, though in the Pig this may not occur (Fig. 322, J) . Hence it may happen that the left duct of Cuvier is left with no (or in the Pig, few) tributaries. In any event it does not disappear, but instead becomes imbedded in the heart muscle as the coronary sinus.

In conclusion of this discussion it remains to state that while these changes have been going on both anteriorly and posteriorly the sinus Venosus has been absorbed into the right atrium of the heart. Hence, since the sinus previously received the anterior and posterior vena cavae and the coronary sinus, this final change means that these three vessels ultimately open separately into the right atrium.

The Pulmonary Veins.——It will be recalled that at 10 mm. the ‘pulmonary veins ehtered the left atrium of the heart by a common trunk. It now remains to state that eventually this trunk is incorporated into the atrium, and its two or more branches achieve separate openings. THE ‘HEART 641

The Heart. —--When last described at 10 mm. this organ consisted of a ventro-posteriorly directed ventricle and antero-dorsally directed atrium. The walls of the former were lined by spongy tissue, the trabeculae carneae, and the chamber was partly divided by a septum growing toward the atrio-ventricular canal. In the latter the fusion of the


Fig. 336. ——-Drawing of fetal Pig heart at nearly full term, opened from the ventral side. B. Semidiagrammatic view of the foramen ovale and septa I and II from the right side. C. Same from the left side. Arrows in all cases represent directions of blood flow according to the most recent conclusions. In B and C the dashed parts of the arrows indicate that a membrane lies between the arrow and the observer. For a complete discussion of the flow of blood in the embryo of the Chick and the Mammal see the text on this topic in the account of the Chick, and Fig.

235X. cushion septa had almost, or quite, completed the division of this orifice into right and left channels. At the same time the atrium had been nearly divided by the septum primum growing from -its antero-dorsal wall. As was indicated, however, this septum had already developed an opening in its antero-dorsal region called the interatrial foramen secundum. The right atrium received the sinus venosus, and the left the single pulmonary vein. Further development may now be described as follows:

The completion of the cushion septum if not accoinplished at 10mm.

soon takes place, This is then quickly followed by the completion of the interventricular septum, and also that of the interatrial septum primum. This latter event closes the interatrial foramen primum, but leaves wide open the recently developed interatrial foramen secundum. The heart therefore is now completely divided into right and left parts except for this latter opening. Meanwhile there has developed another atrial septum just to the right of the first, called the septum secundum, the beginning of which was shown at 10 mm. (Fig. 313). It too is a crescentshapecl sheet extending from the antero-dorsal wall of the atrium along its dorsal and ventral walls. Presently it extends all around these walls and fuses with the septum primum near the atrio-ventricular cushion septum. The new septum secundum, however, fails to become complete in its central region just ventral to the interatrial foramen secundum of the septum primum. This opening in the new septum is called simply the foramen ovale. As reference to Figure 336 will show its position is such that the middle part of the septum primum acts as a valve which can functionally close the foramen ovale. Such closure would obviously occur if pressure were applied to the valve from the left side. We shall return to this matter presently.


Meanwhile as the septa have been thus completed certain further events have taken place. On the sides of the atrio-ventricular canals flaps of tissue have developed, two on the left side and three on the right. These form the atria-ventricular valves (tricuspid right, and mitral left) which hang downward into the respective ventricles. Here their edges have remained attached to some of the traheculae carneae, which in these particular instances become drawn out into strands, the chordae. tendineae, continuous ventrally with the papillary muscles. These, however, are not all the valves of the heart. As previously noted, the truncus arteriosus also becomes divided by a septum into two channels, the systemic and pulmonary, whifli lead respectively from the left and right ventricles. It now remains to state that at its union with the heart the truncus, previous to its division, develops upon its walls two thickenings. Then with the growth of the dividing septum these thickenings are transformed into six semilunar valves, three in each channel.


Finally in the atrial region it has already been remarked that the sinus venosus has been incorporated into the heart on- the right side, and the single pulmonary trunk on the left. This of course causes the separate veins previously opening respectively into the sinus and pulmonary trunk to open directly into the right and left atria. In connection with this it remains to state that as this occurs portions of the right valvula venosa of the sinus are retained as valves of the caval and coronary openings. Also in the later stages of development the atria of the Pig and other Mammals acquire the more or less earlike appendages which have given rise to the name auricle. These it may be recalled occur in the Bird, but only to a slight extent, and not at all in the Frog.


The Fetal and Adult Circulation.—This topic was discussed at considerable length in the case of the Chick, and since essentially the same situation is involved in the Mammal we shall not repeat it here. The student is urged to reread that section at this point. If this advice is followed it will be noted that the chief item of difference cited between the Bird and the Mammal concerned the character of the interatrial opening and its method of closure. There was only one septum in the Bird, corresponding to the mammalian septum primum, and instead of a single opening it contained several. These were closed at hatching by the equalization of pressure on the two sides of the septum which took the stretch out of it, and allowed the perforations to close by contraction. In the Mammal there is the same equalization of pressure at birth. In this case, however, the result is to press the valvelike part of the septum primum against the foramen ovale in the septum secundum, and thus functionally to close that opening. The actual fusion of the parts of the two septa does not occur for several weeks and sometimes several months post partum. Indeed a probe patency may exist permanently, but so long as equal pressure in the atria is maintained, this is of no consequence. The closure of the duct of Botallo was also noted in the discussion of this topic in the section on the Chick, and it was indicated that its permanent closure in the Mammal might occur in about a month. As a matter of fact the time varies in different animals, being 3-4 weeks in the Pig and 6-7 weeks in Man. The relation of the failure of the closure of the septum or of the duct to infantile cyanosis in Man was indicated in the discussion of this topic in the Chick (Figs. 236X, - 336).

The Urinogenital System the Excretory System

The Mesonephros. —— When the excretory system was last discussed the pronephros had entirely disappeared, and the .mesonephros was well developed and functional. Indeed it is relatively larger at this and immediately subsequent stages than when it reaches its peak in absolute size and activity. Thus it continues to grow and funhtion for some time beyond the 60 mm. stage, when it is replaced by the metanephros. In the male of course certain parts of the mesonephros persist permanently in connection with the reproductive system as will be indicated presently.

The Metanephros. —The origin of the permanent kidney or metanephros has already been indicated. Thus at 10 mm. each of these organs consists of a short tubular outgrowth from the postero-dorsal side of the respective mesonephric duct just short of the point where the latter enters the cloaca. At its anterior end this outgrowth, the future ureter, has an enlargement, the anlage of the future pelvis of the kidney. Surrounding this is a concentration of nephrogenic mesoderm (Figs. 296, 323). ‘ '

Further development consists in the forward growth of the ureter and its pelvic enlargement, which carries with it the nephrogenic mesoderm to a position dorso-lateral to the middle of the mesonephros. Meanwhile from the pelvic enlargement there have grown out into the surrounding nephrogenic substance numerous outgrowths which soon become hollow, and which represent the collecting ducts. At the same time concentrations within the nephrogenic mesoderm have become vesicular, and the vesicles send forth outgrowths which become tubular and connect with the collecting tubules. Later these outgrowing secreting tubules become even more convoluted than in the case of those of the mesonephros. Finally, each vesicle becomes invaginated by a glomerulus, and thus is transformed into a Bowman’s capsule. The blood supply to both glomeruli and tubules is entirely arterial in the metanephros. This supply also differs from that to the mesonephros in that it is furnished to each permanent kidney by one main renal artery instead of by several smaller branches.‘

The details of development of the caudal outlets of the ureters and mesonephric ducts can best be described in connection with related parts of the reproductive systems, and will be taken up presently. Before proceeding to that topic, however, there remains a word to say about certain other organs closely connected with the kidneys, though not excretory.

The Adrenals.—As we have seen in the case of the Frog and Chick-, these structures vary considerably in form, but always consist of two parts having specific origins. The medullary substance develops from cells which: have their origin in the neural crests. These cells migrate from the crests along with some of the cells which are to form the sympathetic ganglia, and many of them, after acquiring a special staining capacity, become associated with these ganglia. Others, now called I I i


Fig. 337. —Semi-diagrammatic illustrations of the development of the 1netanephros, the adult ureters and gonoducts, and the separation of the cloaca into anal and urino-genital regions in the Pig. A. Unseparated cloaca with no indication of sex differentiation (about a 10 mm. embryo). B and D. Progressive separations of the cloaca. and development of the urino-genital ducts of the male. C and E. The same process in the female.

chromafiin. cells, come to lie beneath the mesoderm of the coelom. The larger number of these chromafiin cells, however, form a mass adjacent to the cephalic end of the kidneys, where they form the adrenal medulla. Around this medullary substance which becomes arranged in cords, there then accumulate mesodermal cells which constitute the adrenal cortex.

The Reproductive System

The Gonads.—The later development of both, testes and ovaries has been previously described at some length in general and in connection with specific forms. It is essentially similar in all these cases, except in regard to certain aspects of the mammalian ovary, which were also considered previously when mammalian oiigenesis was discussed.


Fig. 338.-— Diagrams representing the descent of a Pig testis. A. Before the testis

has started to move. B. The testis about to enter the scrotum. C. The testis in the scrotum.

We shall not therefore go into this subject again in connection with the Pig.

The Male Urinogenital Ducts. — As we have seen in the case of the Bird, so in the Mammal, the mesonephric duct when no longer needed as a ureter is pressed into service as a sperm duct, 'or 12:15 deferens. Anteriorly the connection between this duct and the respective testis is made through certain mesonephric tubules which are retained for this purpose. They, together with the immediately. adjacent portion of the


Fig. 339. — Diagrams representing the partial descent of a Pig ovary. A. Before the ovary has started to move. B. After it has reached its

definitive position.

mesonephric duct become the e piclidymis. The extreme anterior remnant of the mesonephros may persist as the appendix to the epididymis, while the vestigial caudal remainder occurs as the paradidymis. ' At its caudal end the mesonephric duct when last noted was emptying into the antero-ventral part of the cloaca, which was being separated ofl' as the urinogenital sinus. This division of the cloaca into urinogenital and rectal portions by the urorectal fold is presently completed, and shortly thereafter the cloacal membrane is ruptured. This of course 648 THE LATER DEVELOPMENT OF THE PIG

puts both cloacal parts in communication with the proctodaeum, the opening of the urinogenital sinus being termed the ostium urogenitale, and that of the rectum, the anus (Figs. 337, 340) At the same time that this has been going on the part of the allantois inside the body has been dilating to form the urinary bladder. Presently when the urinogenital sinus, into which the allantois opens, becomes completely separated from the rectum, the cephalic part of the sinus also expands somewhat. Thus this part is in efiect simply added to the posterior end of the bladder, forming its proximal portion. The more caudal portion of the sinus, however, is narrowed instead of dilated, and becomes the urethra. While this has been taking place the end of the mesonephric duct into which the metanephric duct opened has been drawn into the urinogenital sinus, so that these ducts now open separately. Furthermore, the cephalic growth of the metanephros seems to have pulled its duct forward somewhat. The result is that when the separate openings are achieved, that of the metanepliric duct is into the antero-lateral part of the old urinogenital sinus, now forming the base of the bladder. The opening of the old mesonephric duct, however, now the vas deferens, is further posterior into the part of the sinus whichgnow forms the urethra (Figs. 337, 338). ' It remains to add that slightly anterior to the point where the vas deferentia enter the urethra each becomes dilated, and the dilation drawn out slightly to form a small sac, the seminal vesicle. The short remaining part of the vas deferens between the vesicle and its entrance into the urethra is termed the ejaculatory duct. Finally the urethral epithelium gives rise to two glands on the outside of the urethral lumen. but with openings into it, the prostate and the bulbo-urethral or Cowper’.s gland (Figs. 337, 338). This concludes the part of the male urinogenital duct system which is, so to speak, within the body. The remain‘ing portion, together with a description of the ultimate disposition of the testes, will be taken up presently. Before doing that, however, we must return for a moment to the development of the ducts of the female, and certain other considerations.

The Female Urinogenital Ducts. -—- The oviduct originates in_the Mammal, .as it has been seen to in the Frog and Chick, from a thickened ridge of mesoderm lying along each side of the mesonephric duct. This

_ ridge becomes tubular and pulls away from the body wall, to which it ‘ remains attached by’ a fold of peritoneum supporting both ovary and duct. This fold or double sheet of tissue, homologue of the Chick mesovarium, is called‘ the broad ligament, of which more will be said later (Fig. 339). There are of course two oviducts, one on either side, and they at first open separately into the urinogenital sinus. Very shortly, however. their caudal ends fuse to form the vagina. Anterior to this each duct becomes differentiated histologically into a part called the uterus, and still further forward into the definitive oviduct or Fallopian tube. As has already‘ been indicated in our introductory discussion of the Mammal, the degree to which the uterine portions of each duct later fuse to form a single uterus varies in different kinds of animals. In all but the most primitive, however, a slight fusion always occurs to form a region known as the cervix opening into the vagina by a single orifice. In the Sow and other Ungulates this fusion continues a short distance anterior to the cervix to produce a typical uterus bicornis; in Man, of course, the fusion of the uterine parts is complete, giving a uterus simplex. At their anterior ends each oviduct, as has been seen, develops a funnel or infundibulum which may or may not embrace the ovary. In the Sow it does, but in Man it does not. In any event it is of interest to find that this anterior opening develops. not quite at the anterior tip of the original tube, but slightly caudal to it. I

So far as the excretory ducts of the female are concerned the ureter comes to open into the base of the bladder following the division of the cloaca, just as it does in the male. The mesonephric duct naturally has no function in the female, but does persist, along with parts of the mesonephros as a vestige. There are asa matter of fact several of these vestiges in both sexes in addition to those already indicated. Some of these are outside the body, and will be referred to later. Confining ourselves for the moment, however, to those within, it will be well at this point to make some further reference to these remnants.

Internal Vestiges of the Reproductive Systems.——The vestigial appendix of the epididymis and the paradidymis respectively have already been noted. In addition to these in the male, a vestige of the oviduct may be found in the tissue investing the testis, where it is called the appendix of the testis. Posteriorly also a further vestige of the fused parts of -the oviducts may occur as the uterus masculinus. In the female the.undi~fferentiated anterior tip of the oviduct often remains as a small vesicle attached to the duct. Also a vestige of the mesonephros is usually embedded in the broad ligament (mesovariurn) as the epoiiphoron, a structure previously mentioned as occurring in the Chick. Finally ves "tiges of the mesonephric duct. or parts of it, may renriain near the uterus and vagina as the» canals of Gdrtner.

We are now prepared to return to a consideration of the migration of the gonads, and to the development of external features connected with both male and female systems. We shall consider the movement of the gonads first, and we shall begin with the testes.

The Descent of the Testes. -— The student is well aware of course that in the lower animals, such as the Fishes, Amphibia and Reptiles the testes remain within the body at their places of origin. Indeed this is even true in the Birds, which in their way are quite as “ high ” or specialized as the Mammals. It is only within the latter group, however, that the testes radically alter their position so that in most cases they are actually outside the original body cavity all or part of the time. How this comes about is now to be considered.

Both the mesonephros and adjacent testes’ are held against the body wall by a covering of peritoneum. As they grow they push this covering out into the coelom, but the covering does not cut in above them to form a mesentery-like sheet. Instead they simply remain beneath it, such a position being described as retroperitoneal. As development goes on the testis becomes relatively larger and the mesonephros relatively, and finally absolutely smaller, so that the former occupies more and more of the retroperitoneal space. Meanwhile, though the peritoneum (mesodermal epithelium plus connective tissue) does not cut in above the testis and mesonephros, anterior and posterior to them it is drawn out into a longitudinal fold within whose layers runs a bundle of connective tissue fibers. Anteriorly the fold and its bundle of fibers extends from the mesonephros to the diaphragm, and is known as the diaphragmatic ligament (Fig. 338, A). The posterior section of the fold and fibers reaches to the extreme caudal end of the coelom, this section being termed the inguinal ligament of the mesonephros. Here a pair of coelomic evaginations occur, the scrotal sacs or pouches, the cavity in each being termed the processus vaginalis. From the distal wall of each pouch a fibrous strand, the scrotal ligament, proceeds beneath the epithelium to the coelom prop,er. There each scrotal ligament becomes united to the caudal end of the respective inguinal ligament of the mesonephros (Fig. 338). Here it should be incidentally noted that this inguinal ligament has nothing at all to do in origin or function with the inguinal ligament of the adult, known in Man as Poupart’s ligament.

While this is occurring posteriorly the testis is outstripping the mesonephros in growth, and as it does so the attachments of the diaphragmatic and inguinal ligaments of the latter organ become transferred to the former. When this has taken place the united inguinal and scrotal ligaments are given a single name, the gubernaculum. Thus it comes about that a gubernaculum extends from the caudal end of each testis THE REPRODUCTIVE SYSTEM 651

and adjacent epididymis to the bottom of each scrotal sac. We might now briefly complete the story by simply saying that while the diaphragmatic ligament stretches the gubernaculum contracts, thus pulling the testis and epididymis back and down into the scrotal sac. Essentially this is what happens, but as a matter of fact the gubernaculum does not contract. It merely fails to grow, while the other parts do, so that the effect is the same as if it did contract. (It is like the case of the boy holding the cat’s tail. He does not pull it. The cat does that.) In the course of this movement the vas deferens is bent into a loop which passes across the permanent ureter.

It must now be pointed out that since the testis is retroperitoneal it does not actually lie in the coelomic space of the scrotal pouch (processus vaginalis) any more than it lay in the general body coelom. Instead it is pulled down all the way beneath the peritoneal covering which within the pouch is, reflected over it as the tunica vaginalis. Of course in this process the coelomic space within the scrotal sac is elimil nated. While this space existed, however, it was connected with the general coelom by the inguinal canal. From what has just been said it must also be clear that the testes do not really pass into the pouches through the canals, though the existence of the canals permits the movement. They pass back of the canals underneath the peritoneum. After the testes have thus gone into the scrotal sacs the inguinal canals fuse completely shut, except in a few animals to be indicated presently. Nevertheless, it is of interest that this spot evidently comprises a point of weakness which accounts for the occurrence of inguinal hernia in Man. The fact that it occurs in this case, but seldom if at all in the lower animals is probably the result of Man’s erect position. There seem still to be certain advantages in walking on all fours.

It remains to state that the movement of the testes just described does not occur in all Mammals. Thus in the Elephant the testes remain permanently within the body, while in the Rat they pass back and forth, descending during sexual activity. In this connection it is significant that the temperature of the scrotum has been shown to be lower than that of the body cavity. Furthermore, experiment has proven that in animals in which the testes normally remain permanently in the scrotum the retention of the testes within the body results in sterility. Lastly, if in such animals the temperature of the scrotum is‘ artificially raised to that of the body, sterility also results. Thus it appears that in these cases the temperature conducive to spermatogenesis and (or) sperm survival is lower than the normal body temperature. umbilical stalk



Fig. 340.——Drawings of ‘stages in the development of the Pig external genitalia. A and B. The same indifferent stage preceding sexual differentiation. In A the genital tubercle and related parts are turned posteriorly. In B these parts are reflected anteriorly to show their ventral aspects. C’, E and G represent the progressive development of the genitalia of the male at the stages indicated, while D. F and H represent corresponding development in the female.


The DESCEINC Of the Ovary. — In the case of the ovary and oviduct we have noted that these organs are attached to the coelomic wall by a fold of mesothelium and connective tissue called in the Mammal the broad ligament. Within this fold is enclosed the fibrous inguinal liga~ merit of the mesonephros along with the vestiges of the epididymis (epoiiphoron) and vas deferens (canals of Giirtner) . In this instance as development proceeds the inguinal ligament (anterior part of the guber-naculum of the male) apparently exerts no traction. Rather the ovary and oviduct, pulled downward by their weight, stretch both the broad ligament and inguinal ligament within it. Shortly the ovary has moved so far posteriorly that both the oviduct and the ligament are bent around at a considerable angle. When this has occurred the part of the inguinal ligament between the ovary and the bend is called the round ligament of the ovary, and that part between. the bend and the uterus the round ligament of the uterus. In this manner the ovaries come to lie much further back in the body than their point of origin, but unlike the testes they never pass outside (Fig. 339). 3. The External Genitalia, Indifferent Stage. ——As in the case of the very early stages of the gonads themselves so also in this case an in» dilferent stage exists during which sex is indistinguishable. Also, as will presently appear, we find that the same fundamental structures occur in both sexes. It is only with later development beyond the 25 mm. stage that they begin to become differentiated to form the external urinogenital parts of the adult male and female. The parts concerned and their locations are as follows:

As the urorectal fold is dividing the cloaca into the urinogenital sinus and the rectum, the proctodaeum surrounding the original common orifice essentially disappears as such (Fig. 337). Thus the orifice of the urinogenital sinus (the ostium. urogenitale), the edge of the urorectal fold (the rudiment of the perineum) and the anus are brought virtually to the surface in this region. Just anterior to the ostium urogenitale there meanwhile appears a slight elevation known as the genital eminence, which shortly becomes more prominent, and is then called the genital tubercle. Immediately on either side of this tubercle lie a pair of folds called the genital folds. These folds lie not only at the sides of the tubercle, but also extend caudad enough to flank the ostium urogenitale causing the latter to become slit-like. Somewhat further to ei~ ther side of the genital folds are another pair of elevations, the genital swellings (Fig. 340, A, B).

The External Genitalia, Male.—-—The genital tubercle becomes elongated, and grows forward toform the penis. The genital folds from 654 THE LATER DEVELOPMENT OF THE PIG

either side then grow around the penis to form the prepuce, while more posteriorly and to the sides the genital swellings are pushed out by the coelomic evaginations to form the coverings of the scrotal sacs. These presently fuse in the mid-line to produce the single scrotum, the line of fusion constituting a ridge called the scrotal raphe. Up to this point it will be noted that the penis lacks a canal. This is formed by a groove developing along its ventral side, the edges of which soon fuse, and thus is formed the penile urethra, extending from the tip of the penis to the urinogenital sinus. The part of this sinus between this point and the bladder then comprises the prostatic urethra. The line of fusion of the edges of the ostium urogenitale and those of the groove along the ventral or caudal side of the penis forms an extension of the scrotal raphe called the penile raphe (Fig. 340, C, E, G).

The External Genitalia, Female. — The situation in the female is considerably simpler. Starting from the same structures in the indifferent stage we find the tubercle forming a vestigial part; at the anterior border of the ostium urogenitale. It is called the clitoris, and is obviously the homologue of the male penis. The urinogenital sinus itself becomes the vestibule which leads into the vagina formed from the fused ends of the uteri. Upon either side the ostium urogenitale of the vestibule is flanked by the genital folds which have become the labia minora, and slightly more laterally by the genital swellings which have become the labia majora. The former are of course the homologues of the male

prepuce and the latter of the scrotal sac coverings. The term vulva includes all the parts just mentioned (Fig. 340, D, F, [17 ). ’l7

The Skeleton, Teeth, Hair, Hoofs and Horns the Skeleton

I T is not the intention to undertake for the Pig, anymore than we have done for previous forms, a detailed description of skeletal development. It does seem worthwhile, however, to point out a few of the outstanding similarities and differences in this development as it occurs in this animal and in the Frog and Chick.

The Skull. —As in the case of the Frog and Chick the bones of the Pig skeleton may be divided into membrane or dermal bones and cartilaginous bones. On this basis we find in the cranial part of the skull of this animal the same embryonic cartilaginous foundation which we have previously noted, i.e., the basilar plate (fused parachordals and notochord) and the trabeculae. Later of course these develop ossification centers giving rise to the ethmoid and certain of the sphenoid bones. Also added to the cranium from cartilage are the occipitals and the various bones forming the otic and nasal capsules such respectively as the periotics and the naso-turbinals. It will be recalled, however, that the primitive cartilaginous element of the upper jaw, the palato quadrate, still represented in the Bird by the quadrate, has in the Mammal apparently moved into the middle car as the incus. Likewise in the lower jaw a portion of Meckel’s cartilage, in the Mammal is thought to constitute the malleus. All the dermal bones, i.e., those ossifying directly from membrane which occurred in the Bird, exist also in the Pig, with the exception of the quadrato-jugals and parasphenoids. In the lower jaw dermal elements replacing the main remnants of Meckel’s cartilage become ossified and fused together to form the single mandible.

The Vertebrae, Ribs and Sternum.——The concentrations of mesenchyme which are to form the vertebrae alternate with the original somites just as they did in the Frog and Chick, and surround the noto chord. Cartilage forming centers then develop, one about the remains of the notochord, i.e., the future centrum, one in each neural arch and one in each costal process. The cartilage soon spreads from these centers to form a continuous cartilaginous structure for each future vertebra. Then ossification begins in the same centers ivhere cartilage formation began, and spreads until each vertebra consists entirely of bone. The rib cartilage is at first continuous with that of the costal processes, but when ossification begins, the cartilage of the ribs becomes separated from that of the vertebrae, and each rib has its own ossification center. It is of interest that in correlation with the adult condition the cartilage in each rib of the Pig consists of a single piece, instead of two as in some. of the ribs of the Bird. Although the cartilage of each rib is in this case in a single piece, this cartilage ultimately contains more than one ossification center. Thus the ribs in the Pig and other Mammals are like the long bones of the appendages in this class, in that the ends ossify separately from the shafts, forming the so-called epiphyses. As in the Bird the sternum has two cartilage centers attached to the rib cartilage on either side. Later these fuse in the median line.

The Appendicular Skeleton. — Considering the fore limbs first, we find the Pig shoulder girdle differing from that of the Bird in lacking both clavicle and coracoid. The only member of the girdle bones it does possess is the scapula, and this of course is a bone ossified from cartilage.

As regards the long bones of the fore limb (humerus, radius and ulna) we find that in the Mammal the method of ossification in all such bones differs somewhat from that in either the Frog or the Chick. Development begins as usual by the differentiation of cartilage from membrane. Around the middle (diaphyseal region) of this cartilaginous core the former perichondrium, now periosteum, starts to erode the cartilage and to deposit a band of bone. Sincethis band is soon thicker at its middie than at its ends, the remaining central cartilage presently becomes hour-glass shaped. Almost simultaneous with this outer deposit by the periosteum, the cartilage in the middle of the diaphyseal core also begins to be eroded by invading chondrioblasts, and its place is taken by bone deposited by osteoblasts. Soon this endochondral bone and that produced peripherally by the periosteum meet, and the diaphysis is entirely ossified. This bone, however, is all cancellous, and within it three changes occur. First, in the central axis of the diaphysis or shaft the bone is shortly removed and replaced by marrow. Second, about the periphery the original cancellous bone of both central and periosteal origin is also constantly removed and replaced as the diaphysis grows in diameter. Finally, as growth is completed the inner cancellous bone remaining at that time is remade by processes previously described, into compact Haversian systems. Likewise the outer cancellous periosteal bone is replaced by layers of compact periosteal bone. On the basis of this description it might be questioned whether any of the ultimate diaphyseal bone is really endochondral, and it would appear probable that at least what occurs near the mid-region of the diaphysis is not. Nearer the ends, however, the case is different, and for the same reason that this was true in the Chick, i.e., because of the method of longitudinal growth. This method, though fundamentally similar to that in the Bird, differs in certain significant details, and is as follows:

While the processes described above are occurring toward the midregion of the diaphysis each cartilaginous epiphysis is also undergoing ossification in one and sometimes two centers. In this manner there is presently produced in it a single disc of cancellous endochondral bone. At either end of the diaphysis, however, between the bone earlier formed in that location and the respective epiphyseal bony disc, there persists during growth a plate of cartilage known as the epiphyseal plate. These plates correspond in function to the cartilaginous ends of the growing bones of the Chick, i.e., they continue to produce cartilage distally and endochondral bone proximally on the side of each adjacent to the marrow cavity of the diaphysis. Finally, when growth ceases, the epiphyseal plate becomes entirely ossified, and thus joins the already formed bony epiphyses to the ends of the diaphysis. Hence it comes about that, as in the Bird, all of every epiphysis is endochondral. Also somewhat more of the mammalian diaphysis is endochondral because not so much of its interior is ultimately removed as is true in the Bird. For further de tails of bone histogenesis the reader is referred to the account of this process under the Frog, and to the accompanying figures. .

The behavior of the digits has already been referred to in the Pig and we have noted that, as in the Bird, five digits are present in mem brane. In the Pig, of course, the third and fourth are well developed while the first disappears and the second and fifth remain vestigial. The ossification of the znetacarpals and phalanges occurs in these cases from cartilage in the same manner as in other mammalian long bones.

Posteriorly the pelvic girdle is ossified from three cartilages representing the ilium, ischium and pubis. As in the Bird they extend respectively anteriorly, posteriorly'and antero-ventrally. In the Pig, however, the antero-ventrally extending pubic cartilages remain in this position, instead of rotating caudad to lie parallel with the ischia, as in the Chick. Thus when ossification occurs the pubic bones meet one another in the median ventral line, and are held firmly together by ligaments in the manner characteristic of Mammals. The long bones of the Pig hind limb are ossified in the same way as the long bones of the fore limb, 658 OTHER MAMMALIAN STRUCTURES

and consist of course of the femur, tibia and fibula. The four digits, two vestigial, are also formed as in the anterior appendages.

The Teeth

As previously noted, although the Frog does develop teeth, they are small and late in forming so that nothing was said about them, while modern Birds have no teeth at all. It therefore seemed best to postpone


Fig. 341.——A sagittal section through a developing tooth, showing the cells responsible for the secretion of enamel and dentine, and the relations of these cells to those products.

an account of the origin of these structures until we came to the Mammal in which class they attain their fullest development. We shall not attempt to describe the development of any particular tooth since what is true for one is true for all in forms like the Pig or Man, save for variations in shape. '

The Enamel Organs.———As has been previously indicated, at 30 mm. or shortly thereafter the originally single epithelial thickening termed the labio-dental ledge, has divided into two parts. The outer part presently forms the labio-gingival lamina or groove, and the inner one the dental ledge (Fig. 329). This ledge runs along the surface of an elevation which represents the gum, and at intervals along it the formation of the teeth occurs as follows: ‘

_ At each point in the gum region where a tooth is to develop, there occurs a special ingrowth from the dental ledge which penetrates further into the mesenchymé than the non-tooth-forming part of the ledge. The THE TEETH 659

lower part of this ingrowth is expanded into a double-walled inverted cup, known as the enamel organ, which remains connected with the dental ledge for a time by a fairly stout neck (_ Fig. 329). The ledge in turn is also temporarily connected with the oral epithelium by a considerably narrower neck. The cells on the inner wall of the cup are co llumnar in shape, and are destined to secrete the enamel of the tooth.

Hence they are called ameloblasts. Those in the outer wall are at first polyhedral, but soon become flattened, and are known as the epithelium. of the enamel organ. The rather extensive space between the inner and outer walls of the cup is filled with a loose reticulate tissue termed the enamel pulp. Though all enamel organs start out with the relatively simple cap shape that has been indicated, each later assumes the contours characteristic of the crown of the tooth whose enamel it is to form (Five. 329, 341) . .

The Dental Papiila. — As the enamel organ pushes into the mesenchyme the latter necessarily comes to occupy the cup which the organ forms, by which process this mesenchyrne comes to constitute the dental papilla. Of course where the tooth is to have several cusps and roots the enamel organ develops more than one cup, and therefore gives rise to more than one dental papilla and parts subsequently related to it. Presently through multiplication the cells constituting the bulk of a papilla form a rather dense aggregation. At the same time those at its surface adjacent to the ameloblasts of the enamel organ. become columnar like the ameloblasts. These columnar cells of the papilla are then ready for the secretion of their special product, the dentine, and are termed odontoblasts. It thus presently comes about that while the ameloblasts of the enamel organ secrete enamel to form the surface of the tooth, the odontoblasts secrete dentine beneath and adjacent to the enamel. As this activity begins to get under way the enamel pulp lying between the outer epithelium of the enamel organ and its ameloblasts, largely disappears, thus placing these two layers almost in contact. Probably this is significant in bringing the now active ameloblasts that much closer to their external blood supply. At the same time nerves and blood vessels penetrate the central tissue of the dental papilla, which gradually becomes transformed into the pulp cavity of the completed tooth. By the time these processes are under way, the enamel organ has lost all connection with the dental ledge. V A 1

Formation of Dentine. The formation of the dentine by the odontoblasts is in some respects similar to the formation of circumferential bone by periosteum. In both cases it involves the deposition of calcium salts about organic fibers (ossein fibers). In the case of-the dentine, however, the product is not laminated, i.e., in layers, but is continuous. Also no cells are left entrapped within the calcareous substance, and the organic material is less abundant, about 28 percent in dentine as compared with 45 percent in bone. Hence the dentine is harder even than compact bone. Otherwise the materials are similar in that the calcium salts are permeated with ossein fibers, both fibers and salts being produced by the odontoblasts. Likewise there are processes of the odontoblasts which extend into the hard matrix just as the living processes of osteoblasts extend into bone. In this instance, however, the processes all come from the layer of odontoblasts at the inner surface of the dentine, since none are embedded within it, and they are known ‘as the fibers of Tomes (shown but not labeled in Fig. 341,) . They are in general at right angles to the secreted ossein fibers. Obviously the continued production of dentine forces the odontoblasts away from’ the enamel, and also reduces the size of the original pulp cavity, until it becomes not much more than a canal. This canal continues to contain blood vessels and nerve fibers in intimate contact with the odontoblast layer which ultimately becomes inactive and simply lines the pulp canal. Since these inactive odontoblasts send the living fibers of Tomes~ clear through the dentine, it is easy to understand why this substance is sensitive when injured by decay or bored into by a‘dental drill.

The Formation of Enamel.-The enamel, as already indicated. is produced by the ameloblasts of the enamel organ. Because of the relation of these cells to the odontoblasts, moreover, the layer of enamel will necessarily lie adjacent to, and on the outside of, the dentine, or rather a part of it. As will shortly appear, and as reference to Figure 329 will show, the enamel organ, and hence the enamel, only covers the future crown of the tooth, not its roots These are covered by other material whose origin will be described presently. In the region of the crown where the ameloblasts are at work we find that the layer they produce consists of microscopic prisms of very hard calcium salt crystals called dahlite. These are held together by small amounts of a different substance called cement. It seems to be clear that each prism of the enamel is produced by a single ameloblast, and therefore extends all the way from one side of the layer to the other. Since the prisms are not straight, or precisely parallel to one another, however, this is difficult to demonstrate in section. Organic matter is present, but in even smaller amounts than in the dentine, about 5 percent of the total substance being so constituted. It apparenlly consists mainly of fine protoplasmic processes THE TEETH 661

from the ameloblasts which are often called the processes of Tomes (Fig. 341). They evidently correspond to the similarly named processes or fibers put out into the dentine by the odontoblasts. Finally it is obvious that as the tooth grows outward due to the formation of more dentine underneath, the crown will presently be forced through the surface of the gum with the concomitant destruction of the enamel organ. When this has occurred it is evident that no more enamel can ever be formed, and that what has formed will extend only to the gum line. Hence if this hard covering of the exposed surface is later destroyed in any way it is gone forever. Dentine, on the other hand can be, and often is, added to from within, if in later life some of it is removed, as is the case when a tooth is filled. From what has just been said it also follows that unlike the processes of Tomes in the dentine, those of the enamel must disappear when the ameloblasts cease to exist.

The Formation of Cementum.— It has already been noted that only the crown of the tooth is covered by enamel, and that a different material covers the dentine of the root. This material is called cementum, and is produced by the mesenchyme which surrounds the entire tooth and enamel organ previous to eruption. This rnesenchyme is said to constitute the dental sac (Fig. 329). It is only in the neighborhood of the root, however, that the tissue of the sac produces cementum. Here its cells behave almost exactly like the osteoblasts of any periosteum, and the cementum with which they cover the root is essentially the same as periosteal bone. Indeed on its outer side where the cells of the sac are in contact with the jaw bone instead of the teeth, they do in fact add to that bone in the manner of any periosteum. As will be recalled ossein fibers are produced by the cells of such periosteum, and such is the case here, both on the side of the jaw bone, and on that of the cementum. It thus comes about that these fibers actually extend out of the cementum right into the bone of the jaw. In this manner therefore the tooth is very firmly anchored in its socket.

The Permanent Teeth. —- Thus far no mention has been made of more than one type of dentition. As everyone is aware, however, the first set of so-called milk teeth is later replaced by the permanent teeth. This process, however, need not detain us long. The enamel organ for each second or permanent looth arises from the dental ledge near that of the milk tooth. When the ledge disappears, the organ in question lies in a depression of the alveolar socket on the lingual side of the growing milk tooth, but develops no further at this time. Later this “tooth germ ” goes through the same processes as occurred in the case of the 662 OTHER MAMMALIAN STRUCTURES

milk tooth. Meantime the root of the latter is absorbed, and the crown is pushed off by the growing permanent tooth beneath it.

Teeth with Open Roots.— It is of some interest to note that in some animals, notably the Rodents, the incisor teeth continue to grow throughout life. This is made possible by the persistence of a wide root canal and the constant addition of more dentine. To compensate for this the outer end of these teeth is continually worn down by the gnaw


Fig. 342.—Photomicrograph of a mid-sagittal section through a hair root and papilla under high magnification.

ing activities of these animals. This furthermore is made possible by the fact that only the front side of the tooth is covered with enamel. The back side is dentine. Hence since enamel is much harder than dentine the wear is uneven, which gives the end of the tooth a constantly renewed chisel edge. Of course this process makes a continuance of enamel formation also necessary on the front surface of the teeth by the perina nent existence of ameloblasts within the gum in this region, not ‘found in other cases.

Hair

Since hair idevelflops long before the Mammal is born, and is one of the most characteristic features of the class, occurring nowhere else, it seems appropriate tci refer at least briefly to its development.

As previously noted, hair like feathers is an epidermal structure, and again it actually consists of cells, not of a secretion by them like teeth. In this case the cellular character of hair is evident if it is examined under the microscope. Under these conditions its surface lcuticle) reveals transverse rows of wavy lines, which represent the edges of flat cells which overlap one another like the shingles of a roof. Beneath this cuticle are cornified layers of spindle shaped cells and their products, including pigment, which are termed the cortex (Fig. 3452). In many types of hair, including that on the human head, the cuticle and the cortex constitute the entire substance of the shaft. In others, e.g., those of the heard, there is a restricted central region, the medulla, occupied by a few shrunken cells and numerous air spaces. The latter rfive such hairs a more silvery appearance when the pigment disappears with age. The base of each completed hair is contained in a tubular invagination of the epidermis. This invagination is called the hair follicle, and all of the parts which lie beneath the surface of the skin together comprise the root. The walls of this follicle consist oi modified cells of the Malpighian layer of the epidermis, those next to the dermis constituting the ouzer root sheath, and those next to the hair the inner rooi. sheath. The latter is itself usually divided into three separate cell layers, but these need not concern us here. At the base of the root these sheaths merge into dividing cells which are producing the substance of the hair, and pushing it upward through the lumen of the follicle. This mass of dividing cells is itself invaginated by an up-pushing bulblike portion of the dermis containing a blood vessel and known as the hrzir papilla. It is quite similar to the dermal invagination at the base of a leather called the feather pulp, and the function in both cases is to nourish the growing structure (Fig. 342).

Again, as in the case of the feather, the hair originates as a downgrowth of the Malpighian layer termed the hair gernz. A small upgrowth of the dermis invaginates the base or proximal part of this hair germ and constitutes the beginning of 'the hair papilla. Presently the central cells of the germ distal to the base become cornifiecl and thus form the hair. The more peripheral cells of the distal part of the germ soon differentiate into the inner and outer root sheaths of the follicle indicated above. As growth continues the hair presently comes to extend beyond the surface of the skin, until much more of it is outside the follicle than in it. At a point on the follicle near the surface certiain cells of the Malpighian layer constituting the sheaths bu‘d off groups of cells in which fat droplets accumulate, and which constitute the sebaceous glands (Fig. 343) . Just proximal to these there also develop, within the dermis, muscle cells which are attached at one end to the outer root sheath and at the other to the under surface of the adjacent epidermis. They are called the erectile muscles of the hair, and serve to ruflle it. This helps to keep the animal warm, or probably in other cases to frighten its enemies by making it appear larger, as in the Cat (Fig. 343).

Although not essentially

is of interest to note that all types of hairs have relatively fixed periods of life. At the end of this period the hair is shed, and its place taken by a new one. As the time for shedding approaches the epidermal cells at the base of the hair shaft and inner root sheath cease dividing. At the same time those constituting the base of the hair become cornified like those in the main part of the shaft. The hair is then detached from the

' papilla, and easily comes out F18; 343-—‘1,’h°‘°‘_‘1i°1'€’g"‘Pl‘ °f the ?‘‘me of the follicle. Later the new section of hair as in Fig. 342, taken with a . . . . lower magnification to show relations to ha” 15 f91'med In the Same fol‘

neighboring hairs and also to a sebaceous 1ic]e_ The papilla which has gland and erectile muscle. .

shrunken 1S restored, and the remaining live epidermal cells which cover it start to multiply. The

latter presently give rise to both a new inner sheath and hair shaft in a manner similar to the original process.

It is not feasible to give a discussion of the development of these structures in a volume of this size and character. However it may be noted that once more both nails (claws) and hoofs arise as modifications of epidermal cells, involving mainly their cornification. Horns of one type such as those of the Cow are cornified epidermal sheaths supported by bony cores. The antlers of deer on the other hand are mostly bone covered by a layer of skin (dermis and epidermis) which soon dies REFERENCES T0 LITERATURE 665

and is rubbed off. The bony horn itself is shed annually, and renewed by a remarkably rapid growth of nomcartilaginous bone. The two lastnoted structures are not strictly speaking embryological since they never appear until after birth. Because of their developmental similarity in some respects to the other dermal and epidermal appendages, however, it was thought worth while to mention their origins.


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