Paper - Human embryos pathological (1901)

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Mall FP. Human embryos pathological. (1901) Ref. Handb. Med. Sci. 2d ed. 3: 797-.

Human Embryos Pathological


This article is based upon the study of fifty pathological human ova which have been collected by me during the past six years. All of the embryos, with but one exception, have been cut into serial sections, thus permitting of a more careful study than is possible from that of the external appearances alone. As far as possible, I have obtained additional data from the physicians who sent me the specimens; these have proved to be of much value m determining the age of them. Sections were also made of the uterine moles, as well as of nearly all of the embryonic membranes sent me. It is almost needless to .state that whih; I was collecting the pathological specimens a considerably greater number of normal ones came into my possession! "These have also been cut into serial sections, and they have been constantly used for comparison in studying the pathological ova.

The material at my disposal justifies a much more extensive account than I give. The illustrations could also with advantage, be much more numerous. In the present article, my aim is to describe in a connected way the specimens as briefly as possible."

The scattered literature relating to pathological human embryology is very extensive, and in general of not much valrie. From the numerous communications relatine: to young pathological embryos, two groups of paDcrs stand out prominently— those of His and those of Giaeomini The more general article by His is published in Virchow's " Festschrift," vol. i., and that liy Giacomini, isiuMcrkcl und Bonnet's " der Anatomie, viil iy The results of these two authors I have used as a basis after conflrming many of their statements. In general I am able to confirm all of His' statements, while I find some of Giaeomini's obscure. Giacomim s numerous publications are mostly on single specimens, which are usually very young. The nature of his problem as well as the limited amount of material at his disposal, is a sufficient excuse for any misinterpretation he may have made. His latest paper,' published shortly before his death, shows the marked influence the studies of the normal, by Graf Spec and others, have had upon

"Any change which may take place in the embryo after it is well formed, that is, after the second week, is easily recognizable, provided it has not gone too far."

4 more detailed description of the embryos referred to will be found"; an art Mebyniein the Welch " Festschritt," and in Johns Hopkins Hospital Reports, vol. rx.

Specimens of this sort can be divided into two great groups:

(1) those in which the embryo is primarily affected and

(2) those in wliich the chorion is primarily affected. In the first group the embryo is affected and the cliorion normal, while in the second gronj) the chorion is diseased and the embryo partly or whoUv strangulated, due to its impaired nutrition. The earliest stages. His' nodular forms are among the most interesting. Since all of them are vesicular, it might be l)etter to call them vesicular forms. In all of tiiem there is a vesicle which shows many of the characteristics of the umbilical vesicle witli blood islands embedded within its walls. The fact that the blood and the blood-ve.ssels arise in the undiilical vesicle makes it very certain that the vesicular forms represent the remnants of very early embryos. Thei'e have now been studied a suliicient number of young normal embryos to establish the time the blood-vessels grow from the embryo to the chorion. This is at the end of the second week, and the vesicular forms must repres(!nt embryos younger than two weeks, for in none of them have the blood-vessels reached the villi of the chorion. Between the time of the formation of blood in the walls of the lunbilical vesicle and that of their growth into the chorion lies the important stage of the formation of the ))ody of the embryo. Early normal specimens which Peters,' Eternod,^ Siegenbeek van Heukelom and Graf Spec have recently published indicate that the vesicular stages are formed before the body of the embryo is outlined, and also in many instances hand in-hand with the formation of the amnion. If we can use the same reasoning with the vesicular forms which we do with the older ones, then the vesicular must be due to arrested development of earlier and much younger stages than we have as yet been able to study. If the amnion is formed by an invagination of the layer of the embryonic vesicle, as I have previously asserted," then the explanation of a ntunber of the vesicular forms is very easy. But the recent publication of a very young normal embryo by Peters speaks against this. Yet the persistence of an epithelial layer over the vesicle in the vesicular forms, as well as its invagination, indicates that in the specimen I previously described the ectoderm must have broken out of its natural boundaries from a stage like Peters', or that this ectodermal plate upon the umbilical vesicle represents a stage before the formation of the amnion. Either explanation is plausible, liut the first appears to me to be the more likely, for recently Selenka has descrilied an ovum of Hylobates concolors in whicli the amnion almost communicates with the exterior of the ovum.' The ovum Selenka describes is about 1 cm. in diameter with an umbilical vesicle measuring 1 mm.

From all appearances the epithelial covering of the cliorion of early human ova is formed long before the anmiou and embryo are outlined. Judging by the early stages of other manmials, the epithelial covering of the chorion in man must be produced as Rauber'slayer is foimed in them. While the ovum is still wandering down the uterine t\dje, its epithelial covering, or Raul)er's layer, is undoubtedly still smooth, and only grows into villi wdien the cavity of the uterus is reached. Then the syncytial layer is formed, and as evidence accumulates it l)rcomes more and more probable that it is embryonic in origin. 1 have in my collection a young normal ovom from a tuljal pregnancy in which th'e syncytial layer is very extensive, and is growing against a blood clot on one side and ag:dnst noi'mal tubare]iithelium on the other. At certain points its syncytial layer has destroyed the lining epithelial cells of 'the"tid)e and is in direct contact with tla; subepilhelial tissue. The growth of the syncytial layer could be interpreted as growing from I he epithelial cells of the tube to the chorion and from it lr> tlio lilood clot and the lining cells of the tube on the opposite side of the ovum; but why this roundabout and improljuble wav of explanation 'when the direct is so much easier? Moreover, I lie eli;iracleristies of the syncytial layer are so (Iccidi'div "embryonic " that It is uotdifiicult to separate it from tubal eiiithehum when the two e.,i,ie in (-(mtact. Even the nests of partly destroyed tubal cells are very unlike the cells of the syncytial layers.

The quantity of syncytium may be either increased or diminished. In the former instance the buds of syncytium from all portions of the villi as well as from the chorion proper. When there are numerous buds arising directly from the chorion theepithelial cells often become piled "up until the laver is considerably more than two cells deep. The double layer of syncytial cells is also present on the inside of the amnion in a specimen (cxi.Ti.)in which the syncytial cells "ate" through the membranes to the embryo.

The force of the growth of the syncytium may be terrific. It destroys whatever comes in front of it. It grows best when it comes in contact with mother's blood, as a study of numerous specimens shows. Its reaction upon otiier cells is also terrific, for whenever leucocytes come in contact with the syncytium their nuclei fragment, and they disintegrate. When the syncytium forms great masses of cells, so great that its nutrition becomes impaired, the centres of the masses become necrotic. We have here, again, all of the reactions of a parasite battling for its existence. AVhen the growth of the ovum is retarded by the destruction of the embryo, excessive infianunation of the uterus, or other causes, the syncytium may attack the tissues of the chorion and destroy' it in part. This kind of attack is favored most by leucocytic infiltration of the mesoderm of the chorion, as well as by fibrous degeneration of its walls. Yet such an attack is rare, for it appears as if the simple mesoderm of the chorion belongs to the most resistant of tissues. Under certain circumstances it can continue to grow almost bjf itself, for a long time resisting syncytium, leucocytes, and bacteria.

The embryologists of the early part of this century described within the cceloni of the ovum a delicate network of fibrils, the nature of which is not definitely known. This structure, the magma reticulare, is fairlv well marked in normal ova and linalh' disappears wlien the amnion reaches the chorion. This is its story under normal conditions. When, however, the amnion fails to reach the chorion in due time the magma reticulare may become fluid, or in other instances it is converted into a granular mass, or magma granulare. On the other hand, the magma reticulare may be greatly increased in pathological ova of about the fourth week, with or without a diseased chorion. Wlien this condition continues the magma reticulare may become only partly granular, as a number of my specimens show.

At the first appearance one is inclined to consider the magma reticulare as l)eing composed of fibrin. In order to test this ctuestion, I collected a number of fresh specimens, both normal and pathological, hardened them in alcohol and then stained them by means of Weigert's fibrin stain. In no instance did the fibrils of the magma hold the stain. These tests, then, are only negative, giving us no insight as to the nature of the fibrils of the magma.

Not only is the amount of magma found in the cadom excessive, but it may also extend through the ainniim and reach the embryo. In other instances, w hen the embryo remains normal until the sixth week, a magma reticulare may form primarily in the amniotic cavitv and ultimately lierome granular. Whelher or not the reticular magma undergoes disintegration to form the granular remains lo be shown. It is, liowever, noteworthy t liat usually either one or the other exists, but intermediate stages Willi both present are not rare.

In nearly all instances there are scattered throughout the magma numerous cells with relatively small nuclei and a considerable quantity of protoplasm, showing all the characteristics of the blood corpu.scles of the embryo. These are the migrating cells of His. In all pathological specimens it is found that the migrating cells penetrate all id' Ihe tissues of the embryo; in fact, all of the tissues and spaces within the chorion. My specimens show all of the intermediate stages between blood-vessels filled with blood, with few migrating cells in the tissues, to empty blood-vessels with the tissues stuffed with migrating eells. These stages, together with the common morphological appearances of the blood corpuscles and the migrating cells, force the conclusion that the latter are blood corpuscles within the tissues.

It appears as if the blood corpuscles of the emljryo have great power to migrate within the blood s[)aces before the heart is formed. In pathological embryos, when the circulation is retarded or arrested, the corpuscles leave the blood-vessels to form conditions whicli may be termed inflammation of the embryo. As the blood cells leave the blood-vessels to wander through the tissues, the blood-vessels contin\ie to grow in diameter as \veU as in extent, for I have numerous specimens in which the aorta is distended and empty, while in c )t her instances capillary vessels without blood within them, have grown into the villi of the chorion.

Arrested Development of the Embryo with Continued Growth of the Ovum

The specimens which come under this group vary in so many respects that it is impossible for me to consider them from any standpoint except that of their approximate ages when their development was first arrested. Before doing this, I worked through the specimens from many other standpoints — their size, their membranes, and "the condition of then' tissues— only with unsatisfactory results. The general sljupe of the embryos, and their organs however, gave me a clew to their ages when development was arrested ; and when they are considered from tliis standpomt tiie restdts are fairly .satisfactory. Knowin" the time at which the development of the embryos was arrested, the other factors— tissues of the embryo, chorion, and time of the abortion— can easily be taken into consideration. Moreover, in all instances I have repeat edly compared the |>alliological specimens with the normal, my cabinet being well supplied with numerous sets of serial sections of hotli.

There are in my collection two specimens of arrest (jf development at the beginning of the second week (Nos. cxv. and cxxxvi.). A glance at the table shows that one of these specimens is a two-weeks' emljiyo in a fourweeks' ovum; the other a four- weeks' emljryo in a twoweeks' ovum. In one the development of the embryo was arrested at the beginning of the second week, but the chorion continued to grow two weeks longer before the aljortion ; in the other the reverse is the histor}'.

Specimen cxxxvi. appeared to be pathological before it was cut open, but it was found filled with an increased quantity of magma, within which could be seen a nor


Table I. — Arrested Development op the Embryo.*

Dimensions of ovum.


o5 X SOX 10 mm. 20 X 18 X mm . 40 X 30 X 30 mm. 40 X 30 X 20 mm.

B X 30X irunm. 3i X 35 X 1.5 mm .

Time between

last period and abortion.

Two TO Three Weeks.


14 X 11 X 6mm... 30 X27X 22mm...

Mitiriiia reticulare inereased. May:ma reticulare greatly increased.



•Oii days

Three to Forp, Weeks.

1)5 days Amnion has reached chorion.

.K2 (lays Amnion has reached chorion. Embryo very much macerated.

7s davs Mafrma reticulare within coelom.

i)l days ; Mairina reticulare increased.

3."> days ' Maifiiia reticulare fjreatly increased.


tiO X .50 ■ 3(1 mm. . 05 X .55 X 35 inm . . .50 ■■ 40 X 30 mm..


70X 42X 38 mm.. 50 X 60 X 50mm.. 90X75X 50mm..

Four to Five Weeks.



105 X 65 X 65 mm.. SOX 25 X25mm.. 33 X 32 X 32 mm . .

Amniitn has reached the chorion.




83 days.

Magma reticulare greatly increased.

n mm.



70 X 40 X 2(1 mm.. 42 X 30 mm

Amnion has reached the chorion.

15 mm

SI days

Amnion has reached the chorion.

Five to Six Weeks.

16 mm 20mui 20 mm

86 days

S4 days. 12fldays

Cord tilled with a reticular mass. Syncytium within cavity of amnion.


Seven to Nine Weeks.

31 mm

32 mm 35 mm

70 days. 91 days. 126 days.

The Roman numbers given the embryos correspond with the tory of Johns Hopliins University.

record numbers in the cabinet of human embryos in the Anatomical Labora

null einl)rv<> of the fourth week. Since I bad never seen a chori.iu" too small for its embryo, I bad my doubts about the. aecuraev of my observation untd the speeuiien was cut into serial sections. theii, to my surprise, I found an eml)rvo practically normal ot the four-\veel<s sta"-e to corri'spond with the menstrual bistory. 1 lie cho^rion, liowcver, is markedly thickened, with villi, and not in cells. Both chorion and villi contain a great number of blood-vessels which are overtillcd with blood. The syncytium is verv extensive, large buds arising from all parts of the villi as well as from the chorion itself. Comparing it with normal specimens, the syneylium is excessive in quantity, wliich may account for the .rood nutrition of the embrvo. The large amount of embryo blood also speaks for this. The trouble in this specimen seems to lie with the mesoderm of the chorion, which prevented it from expanding sutbciently. This condition was compensated by an excessive growth of the syncytium, which gave sufficient nutrition to the embryo. the entire vascular system of the embryo, lunbiiical vesicle, and chorion is overdistended anil the lieritoneal eavitv of the embryo is also filled with blood. Finally, however, the equilibrium between embryo and chorion was overthrown, resulting ultimately in the abortion. This inequality is also expressed by the excessive quantity of magma within the cadom.

The second s'peciiueii'in which there was an arrest of development at the beghuiing of the second week is No. cxv. Here the development of the embryo is arrested and the chorion has continued to grow. This variety of abnormality is very common, and it is fairly easy to interpret the various steps by which it is brought about. Not only are specimens of this kind easy to interpret, but we have in them the key through which we shall ultimately obtain data regarding the very earliest human embryos. If au ovum four weeks old have within it an embryo two weeks old, why ma}' not an ovum three weeks old have within it an embryo one week old? All the specimens reported in this article speak most decidedly in favor of this hypothesis. In general, this embryo is an exaggerated two-weeks' stage with a fourweeks' amnion and chorion. The great quantity of pus encircling the chorion and cutting off its nutrition, with a conse(|uent atrophy of the sj'ncytium, cuts oil also the nutrition of the embryo, thus graduallj' causing its death. The overtlirow of the equilibrium lietween the emliryo and uterus is indicated by the great quantity of magma within the cfrloin as well as within the amnion. The effect of strangulation of the cmbrj'o is beautifully shown within its tissues. The form of the central nervous system is extri'niel_y simple, like that of an embryo two weeks old, but it is largerand it is solid. Peripheral nerves are not present. The heart is simple, completely tilled with blood ; the lilood-vessels have mostly disappeared. The lunliilical vesicle is relatively small and filled with a solid mass of entoderm cells. Its communication with the body is almost entirely cut off. Within the bod}' there is neither liver nor alimentary canal left. The peritoneal cavity communicates very freel}' with the extra-embryonic ccelom; theic is no ])ericardial cavity. Traces of myotomes and Wolffian bodies an.', still left. Throughout the embr}'o and the magma of llie c(elom and amnion there are scattered cells willi all the characteristics of embryo bluod corjiii.scU'S. Tlii'se are undoubtedly the migra'ting cells already descjilied by His." In tills siieeimen W(; see the later stage of this ]irucess; and, judging by all llie conditions present, ils duration must have been almul Iwii weeks. His dc scribes a similar stage, (lilVering nnly in thai the lime lietween the death of tlic emiiryd and' the alioiliiin is Imir weeks more than in No. cxv.

The two specimens described alun-e imlicali' Ihat there has been an arresi nf ile\eli)pment of sume ]i(irliiins of

the ovum and gi\c si hints ivgaiiling the physiology

of sniiie of llie grniiiisof lissiies." In No. CXV."tli<! priiniiry lesion was iindoiibti'dl\- the eiidometrilis, which de prived the oviini of ils pro),,.,- nntrilion. The .second portion of Table 1. ^ives better daU regarding the primary lesion as well as the probable duration of the Secondary changes within the embryo.

Judging by the general appearance of s|iecimen No. xcvii., it'mighl be considered normal with the exception of the excessive magma reticulare. Sections show, liowcver, that the chorion is fibrous and the embryo is infiltrated with migrating cells which have also invaded the entire cwlom. The age of this specimen, if determined by the embryo and its organs, is not over twenty-eight days, while the menstrual history calls for at least thirty-one days. We have, therefore, to do in this specimen with an "embryo which has undergone pathological changes for at least three days. the chorion is fibrous, and i' am inclined to locate the primary trouble in it. The chorion is the least changeable of all the embryonic tissues, and, therefore, it may follow that a slight alteration in it produces grave consequences. The early changes in the process of degeneration of an embryo are beautifiillv shown in this specimen. The central nervous system is greatly dilated, the boundaries of the abdominal viscera are obscured, and the vascular system is greatly dilated. The entire embryo is filled with migrating cells which show all the characteristics of embryo blood corpuscles.

A stage slightly in ad\ance of the above is shown in specimen No. civ. Here, however, the membranes appear normal, but the walls of the umbilical vesicle are fibrous, the magma is greatly increased and granular, and the embryo is macerated and straightened. The changes within the embryo are much more in advance than in xcvii., the liver tissue being entirely ob.scured. The vascular system is undoubtedly blocked, and the migrating cells "have invaded all of the tissues, including the umbilical cord, to the chorion.

In both of the above specimens the embryos must have been strangulated sufficiently to cause their death, thus permitting the blood corpuscles to leave the vascular system to invade the tissues and the cadom. In specimen cxxii. the primary lesions were not so severe, the embryo continued to grow but not develop, and the amnion continued to dilate until it met the chorion. The primary trouble here again appears to be a fibrous change in the chorion. The central nervous system is distended, the vascular system is dilated, and the aorta is em]ity. The tissues of the embrj-o are partly filled with migrating cells. Specimens ex. and cxi.i. show the same process two or three weeks later. The specimens came from the same woman, who was suffering from leucorrhiea, and in general show the same characteristics. They are both embryos four weeks old which had been retained in the uterus another four weeks after strangulation.

In Nos. ex. and CXLI, the villi of the chorion are almost destroyed, and the chorionic walls are converted into a fleshy mass invaded by leucocytes. The embryos arc atrophied, the organs are obliterated, and the vascular systems are distended. That the process was slow is indicated by the amnion having reached the chorion and the general form of the embryo and its tissues corresponding with that of cxxii. 'The uterine trouble of the mother, the extreme changes of the chorion in both s|ieeimens with almost identical changes in both embryos, ]U'o\e, as much as these specimens can ])rove, that there was a gradual slangulalion of the embryo due to inflamnialion of the ubaine mucous membrane, first affecting and then destroying the villi of the (horion.

The specimens in my collection of embryos of the fifth week lack the data of those of the fourth week, yet something can be made out of them. Undoubtedly the }oimgcst of this gnmp is No. c:xxxni. The \illi of the chorion ajipear normal but have little syncytium at their lips. Bctwciai Ihe villi, upon the chorionic walls, there is an excessive (|uanlity of syncytium. The cadom is complctidy filled with an excessive (|uantity of magma, in which lies the embryo greatly cramped and closely enveloped by the amnion. Terrific changes have taken ])laee within the embryo. In every respect this embryo is like No. xcvii., only it is a few "days older. The migrating cells have invaded the entire enibrvo and at nnraeroiis pomts lliey were leavin- the liody t,') enter the eavily ol the anniion. At these points the epithelium of the embryo is exfoliated. Specimen clxi., whose abortion was caused liy reiieated attempts on the part of the mother, aids materially in locating the beginning of the pathological changes in the ovum. While there is great activity in the leucocytes and syncytium on the outside of the chorion, there is more activity of the migratingceils within the embryo, and this latter condition mus"t be viewed as being secondary.

The other embryos of the tilth week indicate that a slower process has taken place in them. The history of one of them, and the dimensions of the chorion of others also speak for this. the least changed of all the specimens is No. cxxxn. The history of the specimen as well as the dimensions of the chorion indicate that this specimen must have been alive but did not grow to any marked extent during three weeks preceding the abortion. The organs of the embryo are aliout normal in form and structure, with a small number of migrating cells in the tissues and peritoneal cavity. Specimens Lx. and Liv. show slight tissue changes in advance of cxxxii. More marked changes occur in i,xix., which, judging by the size of the chorion, must have been undergoing pathological changes for a number of months before the abortion. In No. Lxxxii. the villi of the chorion are considerably atrophied, while in LXix. the)' are entirely wanting, with tibrous chorionic walls. The erabiyo itself is atrophic and much macerated. The central nervous system is distended, the sharp contour of the organs is lost, and the vascular sj'Stem is distended. Migrating cells have invaded all the tissues, including the peripheral nerve bundles and the umbilical cord.

While most extreme changes will take place in several weeks in pathological embryos of the fourth week, in embryos of the fifth week months are re(|nired to produce corresponding changes. In specimen Lxix. the slow process must have been at work for months, producing all sorts of tissue abnormalities, from multiple papilliform growths of the entire epithelial covering of the body to an atrophied head. In specimen cxxxv. this process of tissue change and organ destruction is still more advanced. The primary lesion of this specimen must also have been in the chorion. The villi are all destroyed while the chorion remains as a thin fibrous membrane infiltrated with leucocytes and a few nests of syncytial cells. The entire chorion is very large, lined by an amnion, and is filled with a jelly-like substance which hardened to the consistence of glycerin-jelly in formalin. The atrophic embryo shows the usual nervous system with the head end of it completely destroyed. The outhne of the organs and. peritoneal cavity is also very indefinite, the entire embryo being filled with migrating cells. The vascular system is more definite than are other portions of the embryo, it no doubt having functioned longest. The head end of the embryo has become greatly atrophied, its front end being converted into a mucoid mass. The eyes have sunken deep into the head but the lenses continued to develop into hard pearls composed of lens fibres. The front end of the chorda is expanded into a large mucoid tumor on either side of which there is a large cartilaginous tumor. All this shows that develoiiment ceased long before the ovum was aborted, but that tissues already established continued to grow and to degenerate into all sorts of masses.

In addition to the groups of embryos of the third, fourth, and fifth weeks, there are several specimens of later date which show that the changes in form and structure are not likely to occur when there is an arrest of development in later stages. Specimen lxxxi. seems to have its primary trouble in the chorion, it being fibrous and invaded by leucocytes as well as syncytium. The amniotic cavity is greatly distended and the embryo is macerated with an ulcerated crest on top of its head. The whole specimen suggests death and destruction of tissues without any indication of further growth of any of the parts.

Specimen cxi.n. also shows the great resistance of an older embryo that has Ijeen dead for .several months before the abortion. The syncytium has also l)een active, liaving uaten into the walls of the chorion and its villi mid liaving entered the cavity of the amnion. Here cells foiin their characteristic double layers again and als(^ invade the tissues of the thickened amnion.

Embryo cxxviii. is a perfect normal specimen with a normal chorion of about the sixtli week, but the history shows that it must be older. The peculiarity of this specimen is the delicate reticulum of fibrils over the embryo within the amnion. It may be that this is Ihe beginning of the granular niagma'frequently found with the amnion of older jiathologieal ova. Of this .same date I liavc another embryo, xciv., with fibrous degeneration, as well as some leucocytic infiltration of the chorion. The embryo is normal in form and the amnion is packed with a mass of granular magma. There are many indications of destruction of the tissues of the embryo, but none of groAvth and regeneration.

No. i.xxix. is similar to xciv. but older. It also has leucocytic (also syncytial) invasion of the chorion, necrosis of the tissues of the embryos and so on. The epithelial covering of the embryo lias partly fallen off, but at the border line of the exfoliation there appears to be an attempt at regeneration. Its lines are not ragged, but the regenerating border is elevated and rounded. There are no cell figures. No. CLii., much like Lxxix., shows a more advanced stage of degeneration. In this specimen the cause of the strangulation of the embryo is to be found in the endometritis, which gradually cut off the nutrition of the chorion, and later aided in destroying the villi.

Among these specimens I may mention here a remarkable one, cxxiv. , in which the nutrition must have been impaired some time during the second month of pregnancy. The entire duration of this pregnancy must have been at least four months. The large chorion has on one side of it a small placenta which is infiltrated with leucocytes. The quantity of syncytium is normal but appears necrotic, a change which may have taken place immediately before the abortion. Between the chorion and amnion there is a large cadom. The walls of the amnion are gieatly thickened. The umbilical cord is thin and greatly twisted. The general form of the embryo is nearly normal, I)ut there are club hands and club feet. The external ear is also rudimentaiy and pointed. If this specimen is compared with a normal embryo of the fourth month it is seen at once how much too small and how distorted this embryo is. In this instance it is interesting to note that accompanying this abnormal embryo there is a diseased placenta, a distended extra-embryonic coelom, and a very thin umbilical cord.

Embryos inth Slight Ahnormality . — In addition to embryos CXXVIII. and xciv. described above, I have several specimens in my collection with slight abnormalities which could not greatly affect the further growth and nutrition of the embryo. No. vi. is undoubtedly a normale embryo, as it was obtained by inducing abortion seventy-seven days after the beginning of the last menstrual period. Its tissues all appear normal with the exception of a small vesicle on the ventral side of the lower tip of the spinal cord. This vesicle is lined with one layer of cylindrical cells; other embryos of the same stage, in my collection, do not possess it. A pathological embryo of about the same age. No. lxxxi. , has a similar dilatation at the lower tip of the spinal cord.

There are in my collection three specimens of hernia of the liver (x., xciv.", xxx.). Embryo in x. is stumpy and poorly shaped, but the tissues appear normal. No. xciv. is abnormal while xxx. is normal.

Degeneration of the Embbto, Leaving only the Umbilical Cokd.— This remarkable group of specimens cau,sed me a great deal of trouble, and not until studying them again and again could I make anything of them. With but one exception (Lxxvii.) they were all found in ova which otherwise appeared normal. The main data are given in Table II. :


Einbryos. Embryos,


Table II.


cxxx .. xxxii.. XX V ... . LXXVII

Diameter of ovum.

3.-1 • 1.-^ ■ V,

\r> ■ 111 • t;

!ii 3.T

711 • 4(1 ■ 311







7 ■' 3 9X3 u ...: 3 I / O.3.

Time lietween

last iieri(jd aud





embryo is greatly needed to keep up I be (•iiuilibriuui between the ovum and uterus and the aliortioii lollops

the earliest stage of this form of degeneration is lepresented in specimen xxxvii. (Figs. 1861 to 1863), which is made up of a very atrophic head of an embryo seated upon the tip of the umbilical cord within the amnion

In i>;eneral, the size of the cord does not correspond to the size of the ovum or to its age when determined from c the last menstrual period. In siieciniens \xxn. and

Fk;. 1861.- Section througli the Heart, Umbilical Vesicle, and Obori<iu of Specimen No. XXXVII. The pharynx and flrst aortic arches are cut across in the head, a, 10 times,

CXXX. the embryonic masses are much alike, and they might well represent the cords of embryos fif the second month. The size of the ovnm in xxxir. calls for this age, but the time between the first lapsed menstrual period and the abortion is much greater. In specimen cxxx. the size of the ovnm, as well as its hi.story, places it in the early part of the third week, but at this time the cord and umbilical vesicle are much less developed than in this specimen.

It appetirs to me that we have in the five specimens given in Table II. five stages of a variety of jiathological em bryos intermediale between ova without any embryos at all and forming embryos which are greatly deformed. At an early stage, after the formation of the amnion, through unknown causes, the embryos die, or, having been originally deformed, cease to grow, while the amnion, cord, and chorion grow on as if nothing had

Fig. 18b:).— Section throueh the Attachment ot the Umbilical Cord and Vesicle t<j the Chorion in No. XXXVII. X 10 times.

The umbilical ve.sicle is attached to the side of the cord but does not extend in anj' way to the embryo. the very rudimentary nervou.s .system, the iibsence of the heart, as avcH as other causes, are snflieient to overtlirow the ftiither growth of this embryo had the tibortion not occurred.

The next stage is represented in specimen cxxx. (Figs. 1864-1866). Here the embryo is already reduced to a mass of cells which no longer contains nervous system or vascular .s_vstem. It naturally dies in consequence of the absence of these important members and thus inteiferes with the equilibrium of the ovum. The cord is filled with blood-vessels and blood, showing again that an embryo must have been present at an earlier ilate.


-Sertioii tinimirh the, Uml.Jliriil Cord and Vesicl Chorion of No. XXX\'II. Id times.

happened. Thcreb.iv the normal villi of il„> chori.di and the comparative absence of nnmnia ridicularc This continues, however, until the eireulution through the

Fill. Isiit. Section tlirouffti the Amnion, Cord, aud Reinnant of the Embryo of No. CXXX. • in times.

Had the amniim not been complete, the remnants of the embryo wotild probably have fallen off, converting this specimen into one rei)resented in the next stage.

The leliition of the aiuuion to the cord makes it probabile that this s]icciraen is nol over three weeks old. The large ccelom also speaks for this. The large and detached uiiibilieal vesicle is ditflcult lo account tor. It may be tliiit the early destruclion of the embryo and the overthidw of the eireulation through the umbilical vesicle may have hasteneil its growth and faviued its separation rrom the unibiliciil cold. Of course it is possilile that the lasting comieetion between the vesicle and umbilical cord wtis separati'd by traumatic means, but a tear is not visible at any ])oint.

A stage slightly more advanced is represented in sjiecimen xxxii. (Figs. 1867 and 1868). Here the amnion tills the ovum completely, the embryo is entirely destroyed, and the cord shows it number of secondary changes.' It may be that this stage is really but little "in advance of the specimen cxxx., as ill it the emliryci ivmniuits -sverc well protected by the amnion. In l)otfi specimens, however, the blood-vessels arc well filled with lilood, and at lioiuts the vascular walls are broken and the cells inlil

FiG. 1805.- Section throusl; the .\mniou. Cord, ami rhorioii o£ No. CXXX

trate the surrounding tissues. These pictures are extremely striking and suggest an attempt at rejiair by the process of inflammation at this early stage. The tip of the cord is intensely stained by the carmine, suggesting very much a section through an ulcerating wound. The nucleated blood cells are out among the mesoderm cells of the cord and become necrotic as they approach its rag,ged edge.

The stage as represented in specimen xxxii. is .sliown in a somewhat advanced form in specimen xxv. , Fig. 1W69. The stump end of the cord is not so ragged as before ; it has become rounded and the larger blood-vessels are not overdistended with blood. It appears as if the stage of great reaction between the blood cells and the necrotic tissue had passed and the wound had nearly liealed.

In the five specimens described above, the morphological characteristics of the chorion, villi, and sj'ncytium

appear normal. The magma reticulare, however, is greatly diminished in quantity or is entirely wanting. With "the exception of the partly deformed embryo, then, there was little to suggest that the specimens are pathological. It appears that the destruction of the embryo with a deficient cjuantity of magma reticulare is the only sign to account for the abortion. Specimen

Lxxvii., however, shows that the ovum can be retained in the uterus for a long time after the embryo has been destroyed, and that under these circumstances decided secondary changes may take place. In this specimen the chorion and amnion have both become more fibrous than normal, appearing as if all the delicate mesoderm spaces Fig. 1866.— Section tbroiigb the At- had disappeared. At the tacliment of the Amnion and Cord to the Chorion of No. CXXX. X 10 times.

there is a nodule which no doiil)t represeiils the reiniiant of the uinhilieal cord, the mesodermal tissue of the villi has also beeoiiic lihioiis, and there are no blood-vessels within them. there is no magma. While this stage has lieen reached on 'the inside of the ovum, the syncytium and leucocytes , on the outside have become most active. With every iiicrea.sed quantity of fresh blood between the villi the syncytium receives new food and continues to grow. Wherever syncytium comes in contact with leucocytes it causes their destruction, as the fragmentation of their nuclei shows. But this cannot continue forever, and finally the syncytium, as well as the leucocytes, attacks the mesoderm of the chorion and its villi, and in specimen Lxvir. all stages of this process are shown. Similar pictures are seen in specimen xciii., which in all probability also belongs to this group of abnormal ova. In cxLii. the syncytial attack is still more; it invades the mesoderm of the chorion and its villi, has entered the cavities of the coelom and amnion, and is attacking the amnion.

The excessive growth of syncytium and its invasion of the maternal tissues, ultimately foi'miug malignant tumors, was first pointed out by Sanger, ' and has since been confirmed numerous times by competent investigators. Recently, however, Neumann '" has shown that not only does the syncytium enter the tissues, and ultimately the circulation of the mother, but it also invades the tissues of the chorion and its villi. This observation I can confirm, but am unable to contribute to its diagnostic value. In general, it appears to me that destruction of the chorion and its villi may be accomplished by the syncytium, but this is exceptional. It appears that when the chorion is attacked by the syncytium there are

10 times.

Fig. 1867.— Section through theC'inl and the Amnion at its Attach! 10 times.

ent to the Chorion

point of juncture between the amnion and chorion

usually great quantities of leucocytes accompanying it, and tliiscondition may also favor the formation of deciduoniata. At any rate the fact is established that the s.yucytium may enter and destroy the chorion and its villi in uterine moles of long standing.

Ova Normal in Form without Embryos and Uterine Moles. — The ten specimens which come under this head differ very much from one another in form and age, but careful consideration of all their structures shovps that they belong together. They are all alike in that the embryos are mis,sin'g, and they must have been destroyed at a very early date; in seven of them this must have taken place before the embryo was six weeks old, as there is no trace of an amnion left ; while in three of them (xcni. and lxxvii.) the amnion is fully formed, but the general appearance of the ova shows that they represent early stages in development.

Table III. gives the general characteristics of the ova which represent all stages of uterine moles. The youngest specimen, Lxxi., is an ovum about two weeks old, normal in every respect, with the exception that the embryo is wanting entirely. Within the ca?lom, however, there is a small nodule about 1 mm. in diameter, which may represent the remnant of the embryonic mass. It is


Embryos, Eiiibryow.


Table HI. — T.\.ble of Ova without Emijuvos and Utehinb ]Mol7':s

of chnrionic mass.


of ctx-'lom


between last

period and









CLllI ...




10 X 9 20X14 30 mm.

r> >: m .50 X ai

4.') X oil 7.5 X 60 40X30 Walnut

X .5 mm . X 6 mm.

X 14 mm. X 20 mm. X 38 mm. X 40 mm. mm

H mm. 16 mill. 24 111111. 15 mm.

4(1 days .

5 mm. 7 mm.

54 days . . 77 days . . 113 days . 279 days .

70 days (?).



None. . . None. .. None... None . . . None. . . None , . . None, . . Present Present





Leucocytic invasion

Leucocytic invasion



.Syncytial inyasion

Syncytial and leucocytic

invasion. Syncytial and leucocytic










syncytial and leucocytic

invasion. Syncytial and leucocytic


Normal . . . .


Excessive . Necrotic...


Excessive . Diminutive Excessive . Excessive .

Excessive .











composed of twisted discs looking much like the dried blood corpuscles of the frog, being pigmented, but thev would not st*iin. If this ma,ss represents the remnants of the eiTibr3'o, it must have died long before the abortion

Another modification of the degenerative process is shown in specimen Lxx. It is an hydatid mole. The chorion is small, collapsed, deeply buried in the specimen, and from it arise enormous villi with very large S|)aces within them. Between the villi thei'e is a considerable quantity of blood which gave nutriment to the excessive syncitium.

To what extent a collapsed ovum may grow is shown in specimen lxxxii. A large solid mass the size of a duck's

Fig. 1868.— Section through the Attachment of the Umbilical Cord to the Chorion in No XXXII. X 10 times.

took place. Embryo xx. also appears normal with the magma normal or slightly increased in quantity and lumpy. These small nodules of magma appeared to the naked eye like remnants of the embryo, but sections of the ovum easily demonstrated the contrary.

The specimens lxxi. and xx. would be considered normal if they had within them a normal embryo. It appears that to the extent, as represented in these specimens, the chorion develops independently of an embryo, but its further growth is affected if no embryo is present! It may be noted that in the ovum of the second week the nutrition must reach the embryo through the fluid of the cielom and thence through the umbilical ve,sicle. Toward the end of the second week the blood-vessels of the embryo reach the chorion, " and at this time nutrition must reach the embryo through its blood-vessels, which now reach to the villi of the cliorion. So if an early embryo is missing we should tind marked changes in the choiion after the beginning of the third week. This proves to be the case in specimen xxix. The walls of the chorion and its villi are fibrous and thickened. The syncytium is very extensive; its borders are no longer sharply defined, and at points it invades the chorion. Many of the islands of syncytium are enclosed in a mucoid, and sometimes fibrinous, envelope. This process is still further increased in specimen lv., which from its size and history belongs to the beginning of the fifth week. The cavity of the C(elom has become smaller, the villi are matted together, and with their surrounding syncytium appear necrotic. There is much blood and fibrin between the yilh and leucocytes have invaded the wall of the chorion In this specimen we have a typical mole which is two weeks older than the specimen lxxi.

large soiia mass tne size of a duck's egg was expelled nine months after the last menstrual peiiod. At the end whicli lay in the os uteri there is an extensive ulceration of the mole; otherwise it is very compact. After it had been hardened, I cut it into sections which, to my astonishment, contained a collapsed chorion sending folds in all directions throughout the specimen. Through the middle of the specimen there are large spaces along the collapsed chorion filled with fresh blood. The opposite walls of the chorion are in appo,sition throughout most of the specimen, and at points thev have grown together. There is no amnion, and on this account I place the beginning of this mole back to the first month of pregnancy. The extensive ramification of the folds of the chorion shows that it must have continued to grow throughout the nine months of its existence, this being made possible by the nutrition brought to it by the fresh blood in its interior. Islands of svncytial cells are located throughout the specimen upon" the" chorionic wall. Tliis syncytium shows active growth and its cells stain well at numerous points where it comes in contact with fresh blood. All the svncytial masses which are distant from the fresh blood are necrotic which is undoubtedly due to the lack of nutrition Nests

Section through the UmhillcaY^rd d Amnion at their Attachment to the Chorion

'^Ll^uZ^tZ '"' .f^Smented nuclei are scattered , 1 f 1 ""' «P«;ein,en. The walls of the chorion

aie not invaded liy the syncytium.

The above group „f 'specimens shows all sta^-es of

chorion""Th contact wftrthe chonon. There are, however, three other specimens,

mens like thus,, m ^^ Inch th. ,.,nbryo was destr yed eavmg oulv the unil.ilieal ,„nl. lxxyr I have already discussed with that gr„up in wlneh the en, nu, IS destroyed, leaving ,)nly the eord (Table H ) and to ,1 I now add xciii. ,n discnssin- it wit], this fiToiin

In speeimen LxxvTi. there is a small stump of the umb.heal eonl left, Avl,ile the elmrion has a lar^e un ni y o blood and syncytium between its villi. At points the chorion and villi are invaded by the syneytinn, In xciir. thi.s process ol destruetion has increase.l, the' chorion IS thickened and irregulur, and it is surr.mnded by hyper rophied villi with great quantities of blood aid syncytium b..tu-een them. (.)ver the entire mass there is a layer of syncytium coyered witli blood and librin then

Within the mesodermal tissue ot the chorion there are occasional islands of svn cytium,

"The two groups of pathological ova, given in Tables II and III,, are undoubtedly caused by an arrest of development and a destruction of the embryo before the t th week of pregnancy. In one of the groups this took place very early belore the amnion had been fully formed and I am strongly inclined to believe that they represent specimens in which the amnion did not form at all —the so-called vesicular forms. In the second group the embryo and amnion were formed, then the embrvo was destroyed, lea\ing the amnion and chorion. In both sets the equilibrium by which the normal growth of the chorion is favored was oyerthrown, due to" the destruction of the embryo. In case the ovum is not aborted, it continues to grow in an irregular fashion, and the chorion or villi either become atrophic or hypertrophic. The syncytium in all cases continues to grow as long as it receives the proper nutrition, and in certain instances it attempts to destroy the chorion and its villi.

Vesicular forms of Pathological Embryos

The different varieties of pathological embryos described above can all be explained as forms of arrested develo])ment of the embryo, its partial destruction or its complete destruction. In all instances the chorion proves to be the most resistant tissue and continues to grow after forming a large cyst-like ovum, but occasionafly collapsing to form a fleshy mole. When the primary trouble is in the embryo, usually the chorion appears normal; but when the primary trouble is in the chorion the embryo is immediately affected, often resulting in its strangulation. ^ In the younger strangulated embryos the tissue reactions are very marked, while in the older strangulated specimens there is a slow and irregular growth, but not development of the organs.

In addition to the atrophic embryos and moles *^here i.s. a group of vesicular forms which are extremely ditiicult to understand. It has frequenth' been asserted that this group represents early pathological embryos, but as yet no positive proof has been brought forward to substantiate tills view. All the specimens at my disposal indicate that the vesicle is the umbilical, for in it there is found the characteristic mesoderm with blood-vessels filled with blood. This is naturally what we would ex m't U> tmd,as the blood-vessels a ise in the Zh i,al v<.sicle and grow iato the ,.mbryo. In lie ve?fe ih """»^il liunian embryo, described- recently by Peters^^. headend';:7.r'"^" amnion completely ^los^d X ^

t wholly covered with mesoderm. There being noi'nial

so can he no ipiestKJU about this specimen

thmU, on this account, that the vounsr


cate that the loin.

logical. Yet this does not indi amnion never communicated with the cieloin. None of the facts are against this hypothesis and

s^.ai; f/, "?' I^V"^'I°8'«> «P«"'n"iB in niy eolleetlo speak tor it. At any rate, the walls of the vesicular ormsare not only formed of a layer of mesodem, in w Inch are embedded blood-vessels and lined with a layer of entoderm cells, but are covered with a layer of epithelium which m a number of specimens form an invaginalon-the amnion. This outer covering of the velicle, Winch I shall term the ectoderm, may represent an eariy normal lorm of the ectoderm or it may represent a displaced ectoderm m a stage as early or earlier than the Peters specimen.

The ectodermal covering ot the V(;siclc is usually present in the vesicular forms and nearly always absent from the umbilical vesicle in the normal embryo. In a large eoUectiou of serial sections of normal embryos I have found It present but once. These facts can be interpreted m either of the ways given above and need not theretore, be discussed further. At any rate, the epithelial layer covering the vesicle in the pathological ova is nearly always present, and in my description of them I .shall assume that it is the ectoderm.

The fact that there is so great a morphological difference between the vesicular embryos and the older pathological embryos makes it likely that some very marked barrier lies between the two varieties. This undoubtedly is the amnion, for in the one it is absent or not closed, and in the other it is present. In order to bring the vesicular forms into any s(jrt of harmony it is necessary to assume that the ectodermal covering of the vesicle is either a displaced amnion or that it is an arrested development of an extremely early normal stage.

That the cavity of the amnion may have communicated at an early stage of its development with the ccelom is indicated by Giacomini in his thirteenth communication,'^ The pathological embryo in the specimen he describes is not entirely encircled by the amnion, for the head of the embryo protrudes through an opening into the calom. A sinrilar, but normal specimen, is described by Siegenbeek Van Ileukelom. This specimen dates froin the end of the second week. The amnion is not complete. In two .sueoessive sections the amnion has in it an opening in the dorsal median line which Van Heukelom believes to be artificial, for free chromatin granules are present in the tissues in the immediate neighborhood of the opening, A similar condition is present in the Peters embryo, as the amnion is not entirely enclosed with a layer of mesoderm but protrudes into the cadom. The first vesicular specimen of my collection which I

Table IV. — ViisicuLAR Forms of Pathological EMninos.


Dimensions of ovunt.

Dimensions of vesicle.

Time between

last period and abortion.


1.0 X .-' ti iiiiii


17 y n mm

',1 / ;j iiiiii

3;j davs

Amnion partly formed.


1.5 X 1 uin:i

41 rlavs

Amnion partly formed.


24 X lU X 9 mm . . , .

20 X 18 X 12 mm

3UX 33 X 13 mm

21 X 16 X 5 mm



6 mm

71 davs

Piirtial amnion.



Multiple amnion.


1 5 ram

Xo amnion.


2.0 X ].') mm

No amnion.


No amnion.


15X10X i'ijnm

30 X 27 X 20 nun

4.0 X 3 X 1.5 mm . ..

14 days

No amnion.


No amnion.


25.0 X 10 mm

shall describe is No. xm. It is a double vesicle, amnion, and \imbilical vesicle attached to the chorion. the ccr lom is filled with a considerable (|\iantity of magma reticulaie. the walls (if the vesicles are fibrous and thickened, and between them there is a I hickened mesoderm. the tissues of the vesicles and llieir cavities are filled with a considerable numlicr of migrating cells. Figs. f870-i«73 show all the layers of the embrjonic mass in their normal posi tion with two large bloodvessels embed<led in the mesoderm. In the enibryoidc stidk the bloodvessels unite into a single tnmk. There is no heart . The stage of this specimen is midway between Graf little earlier than the emThis specimen No. XIII. an intermediate stage between the nodular and atrophic abnormal embryos.

One of the most remarkable specimens ^vln(•ll ma} oe discussed in this connection is No. cxxxiv. I* rom extei

Fig. 1870. — Section thrciufrh tlic Umbilical Vesicle ami Chorion of Specimen No. XIII., Hts' No. XIjIV. Blood corpu.scles are within the cavity of the vesicle. -' 30 times.

Spee's v. II. anil Gle., and a bryo Etcrnod " has describetl recently, shows also that the blood-vessels tilled with blood may grow to tin; chorion before the heart has even existed. This fact is not remarkable when considered in connection with our knowledge of the growth of the blood-vessels from the umbilical vesicle to the body of the embryo to form the heart. Furthermore, Loeb'^ has shown recentlj' that when the heart of embryo fislies is poisoned with KCl a complete set of blood-vessels is developed without any circulation whatever. The fact that blood-vessels may grow into the villi of the chorion without the presence of circulation or blood corpuscles and the great jiower the blood corpuscles possess to wander throvigh any of the tissues of the embryo, exclude to a great extent the mechanical idea of the tirst formation of the blood-vessels.

The beginning of the arrest of development in specimen XIII. must have taken ]ilace after the amnion was

Fig. 1S71 — Section thi lar Veins, TJmhilK al XIII. . 30 times.

Fig. 1S73.-Section through the Umbilical Vesicle as It .loins the Chorion in No. XIII. - :iO times. The larye irregular space in the chorion is a hlooii sjiace which communicates with the veins of the embryo.

iial aijpearances the ovum cannot be over seventeen days old. A few days before the abortion took place the ovum was punctured iinil a clot of mother's blood formed within the cadom. The activity of the leucocytes was terrific, for tiiey encircled the embryo, entered its tissues, and invaded the chorion. We can fairly presume that the embryo was infected with mother's blood somewhere in the neighborhood of the twelfth day of pregnancy, and that its development was partly arrested at that lime. Within the ovum there is a large vesicle which is collapsed (Fig. 1873). It is attached to the chorion b_v means of a firm pedicle. The blood-vessels of the embryo reach to the chorion and enter the villi immediatelv over the attachment of the pedicle to the chorion. In addition to the reaction between ouKh the Ammon, Jugu- t'^f, leucocytes of the mother and the Vesicle, and ( horion of cells of the embryo the most remarkable thing is the arrangement of the germ layers. Fig. 1878 shows in general the collapsed vesicle, composed mostly of two layers with a deep and short invagination of a layci which appeals to be the ectoderm The cells of thi cctodtim aic fiimi thuc to six cells deep and the i\holc Un ( 1 has \ci\ sliai]> boidcis Immcdiatih below this la^ ei theie is a shaij) la\ii of single cubical cells the cntodeim On the side opposite the lUNagin.ition theie is also a double la-\ ci the lunei oi cntodeim the outei ormcsodeim In geneial one can see in this specimen man's <li iiartciistics of tin lr\ eis ol the vesicle completely formed. Had it continued to grow it might have produced an embryo like i xv. described above. An earlier stage could hardly have done this, so we find in

lu. 1ST!— Suli 11 Ihr ii_rii ii,h i imhu md tmhnonic \ esu li .f No ( \\\I\ Till mill 111. il\(siili IS liiin ami Lolli]iseii Thi invagl nation of its « ills iiid the mvitonR-likc bodies ale shonn B, hloid It It L li 11 o(M(s

ot Ko \i (Fi,,s 1S74 and IST-)) The niaiked diflcicnce ism the diuttion ot the iin igmation m xi it isawa^ from the stem, while in ixxxiv. it is toward it. In addition, the ectoderm lining Ihe invagination of embryo CXXXIV., the mesoderm on 'the side near the blood clot," is iirranged in a peculiar manner, suggesting myotomes.

TliiTG are live of them, ami they are surrounded witli embryo blood as well as leucocytes. The wron<f direc tion of the invagination of the ectoderm, and its wn.nnrelation to the "myotonies," make it extremely dilhcuh to interpret this specimen. I am inclined to the opinion that the clot o[ blooil arrested the development of the eni1n-yo when it was in the stage represented by No xi but that the parts continued to grow, shifting'tlii' layer into this abnormal position. The amnion did n„\. cldse the blood-vessels of the cinlnTO failed to form a heart' but (Muitinuedto grow in all diiections through the walls

Fig. 1874.— Section Uimugli the Umbilical Vesicle and its Invagination ol Specimen No. XI. X 51) times. The tliree layers correspond with the ectoderm, mesoderm, and entoderm. The invagination marks the cavity of the amnion.

of the vesicle, its stem, the chorion and some of its villi. The mesoderm continued to develop for a while and produced aborted myotomes.

A specimen similar to the experimental embryo cxxxiv. is No. XI. This specimen has been described in detail in the Joiirital of Morphology, vol. xii,, and in the Johns Hopkins Hospital Reports, voL ix. At that time I used this specimen as a basis upon which to construct a theory of the formation of the amnion. The general arrangement of the layers is given in Figs. 1874 and 1875. Entoderm within, mesoderm with blood-vessels in the middle, and a thick ectodermal plate on the outside. A deep invagination of all three layers is the amnion. A sharp allantois is within the stem.

Specimen Lxxxvii. , Figs. 1876 and 1877, corresponds with xi. as well as with cxxxiv., which is an experiment upon a normal embryo. The age of this specimen is about in the neighborhood of two and a half to three weeks, judging by a normal embrj^o which was within this same ovum. The large vesicle I believed at alterations. Its walls are made up of three distinct layer,s— an (ailer, composed of cylindrical cells; a middle, in which are located blood islands; and an inner coml-Mjscd of Hat cells. With the exception of its thickened walls, it appears as a normal umbilical vesicle which is inverted. The outer epithelial layer does not cover the entire vesicle. On one side thei'e is a deep invagination of all three layers, as shown in the figures.

The pi'esence of this vesicle, in addition to a normal embryo within the ovum, is in itself remarkable. I am inclined to interpret it as an abnormal second embryo. The inA'agination brings it in line with the embryos described above. Remarkable is it that the outer laj'er is so extensive, that the invagination is so small, and that blood islands are included in the walls of the invagination.

Closely related to i.xxxvii. is specimen Lym.,Figs. 1878 and 1879. The mesoderm of the vesicle, pedicle, and chorion is librous and decidedly abnormal in appearance. Within the pedicle there are a few large blood islands.

first to be the umbilical vesicle of the embryo present in the ovum, but sections of them both showed that the embryo had its own normal umbilical vesicle, while the additional vesicle showed marked

Figs. 1876 and 1877.— Sections through the Vesicle and Chorion of Specimen No. LXXXVIl. :< 25 times. A deeper portion of the invagination in Fig. 1876 is shown cut; in cross section in Fig. 1877. Blood islands are in the mesoderm.

Fiii. 1875.— Section through the Stem Unit ing the UmhUical Vesicle with the tho non in No. XI. X 50 times. The cavity within the stem lined with epithelium is the allantois.

Sections through the Vesicle and its Attachment on the Chorion from Specimen N.i 5 1 0-mes W thin the stem there is a sharply deflneil cavity lined with epithelimi /. liitimeb. niio u Lu covered with epi

FIG 1^78 - Sectlons through ve.^|e^--.-^-^ and an hom--gtos:uke space tilled with blood. On one side the stem is covered with epiFiG.'lBra^-The cavity of the Stem, shown in Fig. 1S78, enlarged 50 times.

In the ncigliliorliood of them there is a space lined with a shaTp layer of epithelial cells which might be interpreted as an arrest of development of a stage like Graf Spec's v. H. On the outside of the pedicle, however, there is a distinct layer of epithelial cells, whicli brings this specimen in harmony with the others descriljed above. My interpretation of this specimen is a partial furmation of the amnion with most of the ectoderm on the outside of the vesicle. A similar condition is found in specimen Lxxviii. , Figs. 1880-1883. Here again there is an epithelial layer around the periphery of the stem with a double amnion lined with high epithelium just beneath it (Fig. 1880). There are also blood islands in the mesoderm of the pedicle. Much more marked than any of the above is the condition found in XXIV., Figs. 1883-1885. We have here an ectoderm of varying thickness covering a large share of the vesicle, dipping into the depth at numerous points to produce solid plugs as well as invaginations. There are also nu merous epithelial tubes within the pedicle which do not

FIGS. laSO, 1881, and 1883.— TUe Sections ttroufih the Vesicle and Chorion oi No. rXXVIII. X 10 times. Blood within the cavity of the vesicle. The stem is partly covered with epithelium and there is a double amnion, shown in Fig, 1880.

Fig. 1883.— Section through the Vesicle and Chorion of Specimen No XXiy. X a.j times. There are a multiple allantois and multiple amnion with a thicli layer of epithelium over the vesicle.

communicate with the outer epithelial layer. In this specimen we again have multiple amnion made intelligible from all of the specimens just described. In addition to the specimen in which I In either partial or multiple, we have in xiv.

amnion is Figs. 1880

and 1887, a specimen witliout any amnion whatever. The vesicle is covered with a layer of epithelial cells (ectoderm) wdiich lias fallen oil "io part. There are a few

Fig. 1884.- Deeper Section through No. XXIV. ing Allantois.

sljowing ihe Bram-h

blood islands present. There are also two spaces in the chorion which do not communicate wit.b the main cavity of the vesicle and they are lined with a layer of thin cells. These may be remnants of the amnion, but their appearance differs so from the amnion in other specimens that I am not inclined to accept such an explanation. Below them, embedded in the cliorion, there is a nest of syncytial cells.

With the hypothesis that the epithelial covering of the vesicle and the epithelial tubes in the stem are derived from the ectoderm, all of these pathological specimens of the vesicular form can be explained. I have constantly compared them with numerous sets of serial .sections of normal umbilical vesicles of all ages, and have never found this epithelial covering of the umbilical vesicle of the normal embryo like that in the pathological. In one instance the umbilical vesicle of a pathological embryo of the fourth week (xcvii.)is covered with a layer of epithelial cells.

While we have all variations in the growth of the ectn dermal covering of the vesicle, we also have variation in

. 1HK.5.— A Dei'per section of the Vesicle, showing the Irregular Thickening ol the Ectoderuj and Entoderm.

the growth of its entodernial lining. In general, there is a tendency for the pedicle of the veside to become destroyed, thus liberating the vesicle from the chorion, Haiid-in-haiiil with this ])i'ocess there is an arrest of the development <if the allantois. Usually there is none. My inclination is to consider the cavitv in the pedicles of XIV. and xxi.. Fig. 18«G, as the allantois whicli has been ,se|)ara.ted from the umbilical vesicle. Yet this is only an opinion. In specimen i.xxviii, the cavity of the umbilical vesicle extends well into the clioiion (Fig, 1882), and tills condition may be viewed as dilutatioii of the allantois. In specimen xxiv,. Figs, 1883, 1884, with the multiple amnion, we also have a multiple allantois. Its branches subdivide many times, as the figures sliow^.

In all the patliologiealspecimens there are blood islands in the pedicle. This fact establishes the meaning of the vesicle. It is the remnant of the embryo and its umbilical vesicle. From it the blood-vessels grow to the chodate. If the embryo is fairly well formed before it started to disintegrate, there are blood-vessels with or without blood in the chorion.


ri<in, ami form they to all ovii

in all Uk! pa do not Vfaeli in which the spec The same yo was (Ic

nnens stateme stvoycd

f vesicular nt applies It an earlv

Figs. 1886 and 1887.-Section tlirough the Nodule Vesicle) of Specimen No XIV. X 2.5 times. A tew blood islands! are withm tin stem as well as an enclosed mass of s.racytium. These are also still in the chorion. The nodule is covered with a layer of epithelium which has fallen uff at points.

What I have called umliilical vesicle is undoubted y, in some instances, what Giacomini calls amnion m his earlier communications. the presence ot blood-vesse s is the main evidence for my calling these vesicles umbili

dermal. Otlicr ol),scr\;i1ions, cinimeraled above, also speak tor this ititerpretation.

A single vesicle just, separated from the chorion is found in No. c.xxiir., Fig. ISHi). Tliis vesicle is completely sepa-ratcd from the eliorion with its jiointed end ojiiiosida pointed mound witlnn llie chorion sliowdng its original connecti<m. A similar vesicle is in s])ccimen cxxx., liul the communication may have broken oil'. Another specimen of the same l^ind is cxiAii. The vesicle is fully separated from the chorion and is partly covered with a very thick inesoderiii in which are blood-vessels tilled with blood. Thereare Mood-vessels in the chorion in tinimmediate neighliorliood of the vesiclr, showing that at one time the vesicle must have been wmnected witli it.

A unicpie specimen is shown in No. cxi.iii. There are two large vesicles which do not communicate and are connected with Hie chorion. The structure of their walls could not be made out, as the specimen had been in alcohol many years. The vesicles seem to represent the amnion and umbilical vesicle.

Fig. 1888. — Section through the Vesicle of No. CXXIII. X 25 times. Entoderm, mesoderm, and Ijlood islands are shown.

The primary affection in the vesicular forms seems to be in the neighborhood of the pedicli'. At this iioint all the forces come together. Through it the blood-vessels meet the chorion. Into it the amnion and allaiitois grow. So it is natural that forces which overthrow the development of an early embryo must express themselves at tills pohit. FruidiiiiP. Mull.

Bibliographical References

1 Giacomini ; (ilomale della R. Accadeinia di Medicina, Is'.iT. and Atti K. Accad. delle Sc. di Torino, vol. .xx.xill = Peters : Uel'cr die Eiidiettirag des mensch. Eies, ISHS). 3 Eterncid: Anat. Anz., lid. XV. « Slegenbeek van Heiikelom : His' Archiv, IS'.is. » Graf Spec: His' Archiv, 18911 « Mall : .lourn. Morph., vol. xu. 'Selenka; MenschenalTen, n., Wiesbaden, IS'.B. 8 His: Virchow's Festschrift, i.,,li?H?.

" Sanger Bd. xlix.


Centralbl. f. mil : Verhanill.


'l889, and Archiv f. Gyniikol., ISifi.

cal. The presence of an epithelial covering, especially in the neighborhood of the pedicle, its forming complete, partial, c" multiple invagination into the vesicle or into its stem, are my main reasons for designating it ecto

Fk; isss.-section through the Vesicle and Chorinn in No. XXI. X 25 times. The second vesicle between the larger oiie and the chorion appears to be the stem with a dilated allantois, although it is not attached to the chorion.

d deutsch. Gesellschft. f. Gyniikol., 1897.

iiEternod: Anat. Anz., Bd. xv.. 1898.

12 Giacomini : Merkel u. Bonnet s Ergebnisse, Bd. iv., S. uaii.

i=Van Heukelom: His' Archiv. 1898, S. 27.

n Eternod : Anat. Anz., 1898.

15 Loeb -. Pfliiger's Archiv, Bd. hv., S. 525.

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