Book - Developmental Anatomy 1924: Difference between revisions

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CHAPTER VIII  THE UROGENITAL SYSTEM
The urinary and reproductive systems are associated intimately in development. Both arise from the mesoderm of the intermediate cell mass fnephrotome), which unites the primitive segments with the lateral layers of somatic and splanchnic mesoderm (Figs. 35 S and 128). In the course of development these anlages bulge into the coelom as paired longitudinal ridges, termed the urogenital folds (Figs. 131, 143 and 144).
Vertebrates possess excretory organs of three district types. The pronephros is the functional kidney of amphioxus and certain lampreys, but appears in immature fishes and amphibians only to be replaced by the mesonephros. The embryos of amniotes (reptiles, birds, and mammals) develop first a pronephros, and then a mesonephros, whereas the permanent kidney is a new organ, the metanephros. Whether these glands represent modifications of an originally continuous organ, or whether they are three distinct structures, is undecided, but however this may be the promeso-, and metanephroi of amniotes develop successively, one caudad of the other, in the order named.
I. THE URINARY ORGANS
The Pronephros.  -  When functional, the pronephros consists of paired, segmentally arranged pronephric tubules; one end of each tubule opens into the coelom, the other into a longitudinal collecting duct which drains into the cloaca (Fig. 128 A). Near the nephrostome (the funnel-like opening into the coelom), knots of arteries project into the coelom, forming glomeruli. These filter wastes from the blood into the coelomic fluid which is then taken up by the tubules and carried by ciliary movement into the excretory ducts.
The human pronephros is vestigial. It consists of about seven pairs of rudimentary pronephric tubules, formed as dorsal sprouts from the nephrotomes in each segment, from the seventh to the fourteenth, and perhaps from more cranial segments as well (Fig. 35 B). Y"et the earliest tubules begin to degenerate before the last appear. The nodules hollow out and open into the coelom (Fig. 128 B). Dorsally and laterally, the tubules of each side bend backward and unite to form a longitudinal pronephric collecting duct (Fig. 12S B, A). Caudal to the fourteenth segment no pronephric tubules are developed, but the free end of the collecting duct, by a process of terminal growth, extends caudad beneath the ectoderm (and lateral to the nephrogenic cord) until it reaches the lateral wall of the cloaca and perforates it (Fig. 87). Thus are formed the paired primary excretory {prone phric) ducts. The pronephric tubules begin to appear in embryos of 1.7 mm., with nine or ten primitive segments; at 2.5 mm. (23 segments), all the tubules have developed and the primary excretory duct is nearly complete. In 4.3 mm. embryos, the duct has reached the wall of the cloaca and soon after fuses with it (Fig. 87). The pronephric tubules promptly degenerate, but the primary excretory ducts persist and become the ducts of the mesonephroi.
Fig. 127.  -  Transverse section of a 2.4 mm. human embryo, showing the intermediate cell mass or nephrotome (Kollmann).
Fig. 128.  -  Diagrams illustrating the development of the proncphric duct and proncphric tubules (Felix-Prentiss). A, represents a later stage than B.
The Mesonephros.  -  The mesonephros, like the pronephros, consists essentially of a series of tubules, each of which at one end is related to a knot of blood vessels and at the other end opens into the primary excretory duct (Fig. 87). But the mesonephric tubule differs in two important respects: ( i) the glomerulus indents one end of the tubule, and excreta from the blood pass directly into its lumen; (2) the nephrostomes are transitory and never open into the mesonephric chamber. The mesonephric tubules arise just caudal to the pronephros and from the same general source, that is, the nephrotomes. Only a few of the more cranial tubules, however, are formed from distinct intermediate cell masses, for, caudal to the tenth pair of segments, this mesoderm fuses into unsegmented, paired nephrogenic cords which may extend as far as the twenty-eighth segment (Fig. 132). The primary excretory ducts lie lateral to the nephrogenic cords.
When the developing mesonephric tubules begin to expand, there is not room for them in the dorsal body wall, which as a result bulges ventrally into the eoelom. Thus is produced on each side of the dorsal mesentery a longitudinal urogenital fold, which may extend from the sixth cervical to the third lumbar segment (Fig. 143). Later, this ridge is divided into a lateral mesonephric fold and into a median genital fold, the anlage of the genital gland (Figs. 13 1 and 144).
Differentiation of the Tidmlcs.  -  The nephrogenic cord in 2.5 mm. embryos first divides into spherical masses of cells, the anlages of the mesonephric tubules. As many as four of these are formed in a single segment. Appearing first in the thirteenth to fifteenth segments, the anlages of the tubules differentiate both cranially and caudally. In 5.3 mm. embryos the cephalic limit is reached in the sixth cervical segment, and thereafter degeneration begins at this end (Fig. 130). Hence, the more cranial tubules overlap those of the pronephros. In 7 mm. embryos, the caudal limit is reached in the third lumbar segment.
Differentiation of the tubule anlages progresses in a cephalo-caudad direction (Fig. 130). First, veSicles with lumina are formed (4.3 mm.) from the spherical masses (Fig. i2g AB). Next, the vesicles elongate laterally, unite with the primary excretory ducts, and become S-shaped (Fig. 129 B, C). The free, vesicular end of the tubule enlarges, becomes thin walled, and into this wall grows a knot of arteries to form the glomerulus (5 to 7 mm. ; Fig. 129 D). The wall of the vesicle about the glomerulus is Bowman 's capsule and the two constitute a renal corpuscle of the mesonephros (Fig. 131). The tubule, which was at first solid, is now lined with a low columnar epithelium. In the human embryo the tubules do not branch or coil as in the pig, consequently the mesonephros is relatively smaller. At 10 mm., about 35 tubules are present in each mesonephros and the glomeruli are conspicuous (Fig. 130). Each tubule shows a distal secretory portion and a proximal collecting part which connects with the duct (Fig. 13 1). The glomeruli form a single median column in the gland; the tubules are dorsal and the duct is lateral in position. Ventro-lateral branches from the aorta supply the glomeruli (Fig. 212), while the posterior cardinal veins (Fig. 145), dorsal in position, break up into a network of sinusoids about the tubules.
Fig. 129.  -  Diagrams showing the differ- Fig. 130.  -  The anlages of the urinary or entiation of a mesonephric tubule (Felix- gans in a 10 mm. human embryo, as seen Prentiss). L. lateral; M. median. from the left side (adapted by Prentiss).
The pronephric duct, now termed the mesonephric, or Wolffian duct, is solid in 4.3 mm. embryos. A lumen is formed at 7 mm., wider opposite the openings of the tubules. The duct is important, as the ureteric anlage of the permanent kidney grows out from its caudal end, while the tube itself is transformed into the chief genital duct of the male.
That the human mesonephros is a functional excretory organ is plausible (Bremer, 1916), but not proved. Degeneration proceeds rapidly in embryos between 10 and 20 mm. long, beginning cranially (Fig. 148). New tubules are formed at the same time caudally (Fig. 130). In all 83 pairs of tubules arise, of which only 26 pairs persist at 21 mm., and these are usually broken at the angle between the collecting and secretory regions. How the genital system utilizes them for new purposes will be traced in a later section (p. 156).
The Metanephros.  -  The essential parts of the permanent kidney are the renal corpuscles (glomeruli with Bow^man - s capsules), secretory tubules, and collecting tubules. Like the mesonephros, the metanephros is of double origin. The ureter, pelvis, calyces, and collecting tubules are outgrowths of the mesonephric duct. The secretory tubules and the capsules of the renal corpuscles are differentiated from the isolated, caudal end of the nephrogenic cord and thus have an origin similar to that of the mesonephric tubules.
In embryos of about 5 mm. the mesonephric duct makes a sharp bend just before it joins the cloaca, and it is at this angle that the ureteric evagination appears, dorsal and somewhat median in position (Fig. 139 B, C). The bud grows at first dorsally, then cephalad. Its distal end expands and forms the primitive pelvis; its proximal elongated portion is the ureter. The pelvic anlage grows into the lower end of the nephrogenic cord (Fig. 132), which, during the third month, becomes separated from the cranial end. The nephrogenic tissue forms a cap about the primitive pelvis, and, as the pelvis grows cranially, is carried along with it.
Fig. 132.  -  Reconstruction of the metancphric anlages in a human embryo of about 9 mm (after Schreiner).
In embryos of g to 13 mm. the pelvis, having advanced cephalad through three segments, attains a position in the retroperitoneal tissue dorsal to the mesonephros and opposite the second lumbar segment. Thereafter, the kidney enlarges both cranially and caudally without shifting its mean position (Fig. 154).
Fig. 133.  -  Diagrams showing the development of the primitive pelvis, calyces and collecting tubules of the metanephros (adapted by Prentiss).
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Differentiation of the Ureteric Anlage.  -  Primary collecting tubules grow out from the primitive pelvis in 10 mm. embryos. Of the first two, one is cranial, the other caudal in position, and, between these, two others usually appear (Fig. 133 B, C). From an ampullary enlargement, at the end of each primary tubule sprout off two, three, or four secondary tubules. These in turn give rise to tertiary tubules (Fig. 133 D) and repeated until the fifth month of fetal life, when it is estimated that twelve generations of tubules have been developed.
The pelvis and the primary and secondary tubules enlarge greatly during development. The two primary expansions become the major calyces, and the secondary tubules opening into them form the minor calyces (Fig. 134). The tubules of the third and fourth orders are taken up into the walls of the enlarged secondary tubules so that the tubules of the fifth order, 20 to 30 in number, open into the minor calyces as papillary ducts. The remaining orders of tubules constitute the collecting tubules which form the greater part of the medulla of the adult kidney.
When the four to six primary tubules develop, the nephrogenic cap about the primitive pelvis is subdivided and its four to six parts cover the end of each primary tubule.
As new orders of tubules arise, each mass of nephrogenic tissue increases in amount and is further subdivided until finally it forms a peripheral layer about the tips of the branches tributary to a primary tubule. The converging branches of such a tubular  - tree -  constitute a primary renal unit, or pyramid, with its base at the periphery of the kidney and its apex projecting pnto the pelvis. The apices of the pyramids are termed renal papilla:, and through them the papillary ducts open. The nephrogenic tissue forms the cortex of the kidney, and each subdivision of it, covering the tubules of a pyramid peripherally, is marked off on the surface of the organ by grooves or depressions. The human fetal kidney is thus distinctly lobed, the lobations persisting for several years after birth; this condition is permanent in reptiles, birds, and some mammals (whale; bear; ox). The primary p^ - ramids are subdivided into several secondary and tertiary pyramids. Between the pyramids, the cortex of nephrogenic tissue dips down to the pelvis, forming the renal columns (of Bertin). The collecting tubules, on the other hand, extend out into the cortex as the cortical rays, or pars radiata of the cortex. In these rays, and in the medulla of the kidney, the collecting tubules run parallel and converge to the papillae.
Fig. 134 -  Reconstruction of the ureter, pelvis, calyces and their branches from a 16 mm. human embryo (Huber). X 50.
Differentiation of the Nephrogenic Tissue.  -  In stages from 13 to 19 mm., the nephrogenic tissue about the ends of the collecting tubules condenses into spherical masses that lie in the angles between the buds of new collecting tubules and their parent stems (Fig. 135). One such metanephric sphere is formed for each new tubule. The spheres are converted into vesicles with eccentrically jilaced lumina. The vesicle elongates, its thicker outer wall forming an S-shaped tubule which unites with a collecting tubule, its thin inner wall becoming the capsule (Bowman - s) of a renal corpuscle.
The uriniferous tubules of the adult kidney have a definite and peculiar structure and arrangement (Fig. 136 4 l). Beginning with a renal corpuscle, each tubule forms a proximal convoluted portion, a \J-shaped loop (of Henle) with descending and ascending limbs, a connecting piece, which lies close to the renal corpuscle, and a distal convoluted portion continuous with the collecting tubule. These parts are derived from the S-shaped anlage, which is composed of a lower, middle, and upper limb. The middle limb, somewhat U-shaped, bulges into the concavity of Bowman - s capsule (Fig. 136 B). By differentiation the lower portion of the lower limb is converted into Bowman - s capsule, and ingrowing arteries form the glomerulus (Fig. 1^6 B, C). The upper part of the same limb by enlargement, elongation, and coiling becomes the proximal convoluted tubule. The neighboring portion of the middle limb forms the primitive loop (of Stoerck) ; the base of the middle limb gives rise to the connecting piece, and the rest of it, rvith the upper limb of the S, comprises the distal convoluted tubule. The primitive loop of Stoerck includes both the descending and ascending limbs of Henle - s loop and a portion of the proximal convoluted tubule as well. Henle - s loop is differentiated during the fourth fetal month and extends from the pars radiata of the cortex into the medulla (Fig. 137). The concavity of Bowman - s capsule, into which grow the arterial loops of the glomerulus, is at first shallow. Eventually, the walls of the capsule grow about and enclose the vascular knot, except at the point where the arterioles enter and emerge (Fig. 135,4 and 5). Renal corpuscles are first fully formed at the end of the second month. The newer corpuscles differentiate peripherally from persisting nephrogenic tissue, and this may continue for some time after birth; hence, in the adult, the oldest corpuscles are those next the medulla. Reconstructions of the various stages in the development of the uriniferous tubules are shown in Fig. 138.
Fig. 135 - (Huber). The left half of each figure represents an earlier stage than the right half.
Fig. 136.  -  Diagrams showing the differentiation of the various parts of a human uriniferous tubule (adapted by Prentiss). A, From an adult; B, C, from embryos.
Fig. 137.  -  Diagram showing the relation of Bowman - s capsule and the uriniferous tubule to the collecting tubules of the metanephros (Huber), c, Collecting tubule; e, end branches of collecting tubules; r, renal corpuscles; n, neck; pc, pro.ximal convoluted tubule; dl,al, descending and ascending limbs of Henle - s loop, /; dc, distal convoluted tubule; j, junctional tubule.
Fig. 138.  -  Reconstructed stages in the development of the human metanephric tubule at
the seventh month (Huber). X 16.
Anomalies.  -  The kidneys may fail to ascend from their embryonic position in the pelvis. Absence of one kidney is not infrequent. The kidneys sometimes fuse, either completely into a disc-shaped mass, or partially by cortical union (V/cm - -i/zoe ;
in such cases the ducts usually are bilateral. Double or cleft ureters and pelves occur.
Renal Cysts (cystic kidney) result from the primary non-union of uriniferous and collecting tubules, or by the cystic degeneration of secondarily detached tubules (Kampmeier, 1923).
Differentiation of the Cloaca.  -  In embryos of i . 4 mm., the cloaca, a caudal expansion of the primitive entodermal canal, is in contact ventrally with the ectoderm, and the area of union constitutes the cloacal membrane (Fig. 139 A). This membrane at first extends from the tail bud to the body stalk (Figs. 71 and 95), and occupies a region corresponding to the hind end of the primitive streak (Figs. 44 and 58). Later, .
Fig. 139.  -  Reconstructions of the early human cloaca (Pohlman-Prentiss). X about 50. .4 3.5 mm.; B, 4 mm.; C, 5 mm.; D, 7 mm.
Its expanse is diminished in both directions (Figs. 96, 141 and 142). Ventro-cephalad, the cloaca gives off the allantoic stalk, receives the mesonephric ducts laterally, and is prolonged caudally as the tail-gut (Fig. 139 B).
The saddle-like partition between the intestine and allantois grows caudally, dividing the cloaca into a dorsal rectum and ventral, primitive urogenital sinus (Figs. 139 to 142). The division is complete in embryos of u to 15 mm., and at the same time the partition, fusing with the cloacal membrane, divides it into the anal membrane of the gut and the urogenital membrane (Fig. 142). The intermediate tissue represents the body of the primitive perineum. At u mm., according to Felix, the primitive urogenital sinus by elongation and constriction is differentiated into two regions: (1) a dorsal vesico-urethral anlage which receives the allantois and mesonephric duct, and is connected by the constriction with (2) the phallic portion (Figs. 140 and 141). The latter extends into the phallus of both sexes and forms a greater part of the male urethra (Fig. 142), as described on p. 164.
Fig. 140.  -  Reconstruction from a 12 mm. human embryo, showing the partial division of the cloaca into rectum and urogenital sinus (Pohlman-Prentiss). X 65.
Fig. 141.  -  Reconstruction of the caudal portion of an 11.5 mm. human embryo, showing the differentiating rectum, bladder and urethra (Keibel-Prentiss). X 25.
The vesico-urethral anlage enlarges and transforms into the bladder and into either the entire female urethra or the prostatic and membranous male urethra. In 7 mm. embryos the proximal ends of the mesonephric ducts are funnel shaped, and, at 10 mm., eoincident with the enlargement of the bladder, these ends are taken up into its wall until the ureters and mesonephric ducts acquire separate openings (Figs. 141 and 142). The ureters, having previously shifted their openings into the mesonephric ducts from a dorsal to lateral position, now open into the vesico-urethral anlage lateral to the mesonephric ducts. The lateral walls of the bladder anlage grow more rapidly than its dorso-median urethral wall; hence the ureters are carried cranially and laterally upon the wall of the bladder while the mesonephric ducts open close together on a hilloek, Muller's tubercle, into the dorsal wall of the urethra (Fig. 142). Thus an area, roughly bounded by the openings of the ureters and the mesonephric (ejaculatory) ducts, is mesodermal. Besides the trigone of the bladder the area includes a proximal segment of the urethra (Fig. 160 C). In the male, this stretch corresponds to the upper portion of the prostatic urethra; in the female, it includes much of the shorter definitive urethra.
Fig. 142.  -  Reconstructions of the caudal end of a two-months -  human embryo, showing the complete separation of the rectum and urogenital sinus and the relations of the urogenital ducts (Keibel-Prentiss). X 15.
The narrowed apex of the bladder, continuous with the allantoic stalk at the umbilicus, is known as the urachus (Fig. 157). It persists as the solid, fibrous middle umbilical ligament (Fig. 199). Contrary to earlier views, the allantois contributes nothing to the bladder or urachus (Felix, 1912).
The transitional epithelium of the bladder appears at 10 weeks. The circular and outer longitudinal layers of muscle develop at the end of the second month. The inner longitudinal muscle layer is found at 10 weeks and the sphincter vesicse in fetuses of three months.
Anomalies.  -  A conspicuous malformation is that of a persistent cloaca, due to the failure of the rectum and urogenital sinus to separate. The bladder sometimes opens widely onto the ventral body wall and is everted through the fissure; a urogenital aperture corresponding to the upper extent of the primitive cloacal membrane would cause this condition (Fig. 139 C, D). At times, the urachus remains a patent tube, opening at the umbilicus as a urinary fistula. Portions of its epithelium which fail to degenerate may form cysts.
Fig. 143.  -  Reconstruction of the male urethra and associated parts, from a fetus of four months (after Broman). X 13.
Accessory Genital Glands.  -  The prostate gland develops in both sexes as outgrowths of the urethra, both above and below the entrance of the male ducts (Fig. 143). Hence, the upper portion, at least, must be mesodermal in origin. The tubules arise at ten weeks in five distinct groups and total an average number of 63. The surrounding mesenchyme differentiates both connective tissue and smooth muscle fibers, into which the anlages of the prostate grow. In the female, the homologue is rudimentary; these isolated para-urethral ducts (of Skene) number at most three.
The bulbo-urethral glands (of Cowper) arise in male embryos of nine weeks as solid, paired epithelial buds from the entoderm of the urethra (Fig. 143). The buds penetrate through the mesenchyme of the corpus cavernosum urethree, about which they enlarge. The glands branch, and, at four months, the epithelium becomes glandular. The vestibular glands (of Bartholin) are the homologues in the female of the bulbo-urethral glands. They appear at the same age as the male glands, grow until after puberty, and degenerate after the climacterium.
u. THE GENITAL ORGANS .
A. Indifferent Stage .
The Gonads.  -  In origin and early development, the ovary and testis are identical. The urogenital fold (p. 135) is the anlage of both the mesonephros and the genital gland (Figs. 392 and 144). At first two-layered, its epithelium in embryos of 5 mm. thickens over the ventro-median surface of the fold, becomes rciany-layered, and bulges into the coelom ventrally to produce the longitudinal genital fold (Fig. 13 1). The genital fold thus lies mesial and parallel to the mesonephric fold. Large primordial germ cells are found in the entoderm of the future intestinal tract; at 3.5 mm., these migrate into the dorsal mesenteric epithelium and thence into the epithelium of the genital fold. It is undecided whether or not the definitive germ cells of the genital glands are descendants of such elements. At 10 to 12 mm., the genital anlage shows no distinctive sexual differentiation (Fig. 145); there is a superficial eph/je/ia/ layer and an inner epithelial mass of somewhat open structure owing to the great development of the suprarenal glands and metanephroi, the cranial portions of the urogenital folds, at first parallel and close together, are displaeed laterally. This produces a double bend in each fold, which, in 20 mm. embryos, shows a cranial longitudinal portion, a transverse middle portion between the bends, and a longitudinal caudal portion (Fig. 160 A). In the last-named segment, the mesonephric ducts course to the urogenital sinus, and here the right and left folds fuse, producing the genital cord (h^ig. 154). As the genital glands increase in size, they become constricted from the mesonephric fold by lateral and mesial grooves until the originally broad base of the genital fold is converted into a stalk (Figs. 149 to 151). This mesenterial attachment extends lengthwise and forms in the male the mesorchium , in the female the mesovarium.
Fig. 144.  -  Ventral view of the urogenital folds in a human embryo of 9 mm. (Kollmann).
Fig. 145.  -  Transverse section through the mesonephros, genital gland and suprarenal gland of the right side; from a 12 mm. human embryo (Prentissf. X 165.
The Primitive Genital Ducts.  -  The mesonephric ducts, with the degeneration of the mesonephroi, become the male genital ducts; their origin and early history have been deseribed (pp. 137 and 139).
Both sexes also develop a pair of female ducts. In embryos of 10 mm., these Mullerian ducts arise as thickened ventro-lateral grooves in the urogenital epithelium, near the eranial ends of the mesonephroi (Fig. 146 A).
Fig. 146.  -  Transverse sections through the anlage of the right Mullerian duct from a 10 mm. human embryo (Prentiss). X 250. A, Cranial end of groove; B, three sections caudad.
Fig. 147.  -  X - entral dissection of an 18 mm. pig embryo, to show the growing Mullerian ducts (Prentiss). X 7.
Fig. 148.  -  Ventral dissection of a 24 mm. pig embryo, showing a later stage in growth of the Mullerian ducts (Prentiss). X 6.
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Fig. 149.  -  Section through the left testis and mesonephros of a 20 mm. human embryo (Prentiss). X 250.
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Caudally, the dorsal and ventral lips of the groove close and form a tube which separates from the epithelium and lies beneath it (Fig. 146 B). Cranially, the tube remains open as the funnel-shaped ostium abdominale of the Mullerian duct. The solid end of the tube grows caudalward, beneath the epithelium and lateral to the mesonephric, or male ducts (Figs. 147 to 149). Eventually, by way of the genital cord, the Mullerian ducts reach the median dorsal wall of the urogenital sinus and open into it (Figs. 142 and 160 A). In the lov/est vertebrates, the Mullerian duct arises by a longitudinal splitting of the mesonephric duct.
Embryos not longer than 12 mm. are thus characterized by the possession of indifferent genital glands and both male and female genital ducts. There is as yet no sexual differentiation.
B. Internal Sexual Transformations .
Differentiation of the Testis.  -  In male embryos of 13 mm., the genital glands show two characters which mark them as testes: (1) the occurrence of branched, anastomosing cords of cells, the testis cords; (2) the occurrence between epithelium and testis cords of a layer of tissue, the anlage of the tunica albuginea (Fig. 149). According to Felix (1912), the testis cords of man are developed suddenly from the loose, inner epithelial mass by a condensation of its cells; on the contrary, xMlen (1904) holds that in the pig and rabbit they grow in from the surface epithelium The cords converge towards the mesorchium, where they form the dense, epithelial anlage of the slenderer rete testis. Two or three layers of loosely arranged cells between the testis cords and the epithelium constitute the future tunica albuginea.
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Fig. 150.  -  Section through the left testis of a fetus of fourteen weeks (Prentiss). X 44.
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The testis cords soon become rounded and are marked off by connective-tissue sheaths from the intermediate cords, which are columns of undifferentiated tissue lying between them (Fig. 150). Toward the rete testis, the sheaths of the testis cords unite to form the anlage of the mediastinum testis. The testis cords are composed chiefly of indifferent cells, with a few larger germ cells. The cells gradually arrange themselves radially about the inside of the conneetive-tissue sheath as a many-layered epithelium; during the seventh month, a lumen ajDpears and extends toward the rete testis to meet lumina which have formed there. Thus the solid cords of both are converted into tubules. The distal portions of the testis tubules anastomose and form the tuhnli contorti. Their proximal portions remain straight, as the tuhuli recti. The rete testis beeomes a network of small tubules that finally unite with the efferent duetules.
The primordial germ cells of the testis eords form the spermatogonia of the seminiferous tubules, and from these, at puberty, are probably developed the later generations of spermatogonia, although some claim that the early germ cells all disappear, to be replaced later from the indifferent elements. The indifterent cells of the tubules become the sustcntacnlar cells (of Sertoli) of the adult testis. Certain cells of the intermediate cords, epithelial in origin, are transformed into large, pale cells, which, after puberty, are numerous in the interstitial connective tissue and hence are designated interstitial cells. The intermediate cords, as such, disappear, I:)ut the connective-tissue sheaths of the tubules unite to form septula which extend from the mediastinum testis to the fibrous tunica albuginea.
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Differentiation of the Ovary.  -  The primitive ovary, like the testis, consists of an inner epithelial mass, bounded by the parent peritoneal epithelium. The ovarian characters ajjpear much more slowly than those of the testis. In fetuses of ten to eleven weeks, the inner ei^ithelial mass, composed of indifferent cells and primordial germ cells, becomes less dense centrally and bulges into the mesovarium (Fig. 151). There may be distinguished a dense, outer cortex beneath the epithelium, a clearer medullary zone containing large germ cells, and a dense, cellular anlage in the mesovarium, the primitive rete ovaru, which is the homologue of the rete testis. Neither epithelial cords nor tunica albuginea are developed at this stage, as in the testis.
.Later, three important changes take place: (i) There is an ingrowth of connective tissue and blood vessels from the hilus, resulting in the formation of mediastinum and septula. (2) Most of the cells derived from the inner epithelial mass are transformed into young ova, the process extending from the rete ovaru peripherally (Fig. 151). (3) In fetuses of three to
five months, the ovary grows rapidly, owing to the formation of a new peripheral zone of cells, derived perhaps in part from the peritoneal epithelium. At the end of this period the septula line the epithelium with a fibrous sheath, the anlage of the tunica albuginea. Hereafter, such folds of the epithelium as form do not penetrate beyond the tunica albuginea and all cells derived from this source subsequently degenerate. This new peripheral zone, according to Felix, is always a single cellular mass in man, cords, or  - Pfluger - s tubes, -  never growing in from the epithelium. Generally, it has been believed that the primary follicles are derived from the subdivision of such cords.
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Fig. 152.  -  Section through the ovarian cortex of a five-months' fetus (De Lee).
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Fig. 151. -Section through the left ovary of a three-months -  fetus (Prentiss). X 44.
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Coincident with the origin of a new zone of cells at the periphery of the ovary, goes the degeneration of young ova in the medulla. Invading connective tissue separates these germ cells into clusters, or cords, which degenerate and leave only a stroma of fibrous tissue in the medulla. Late in fetal life, indifferent cells, by surrounding the young ova of the cortex, produce primordial follicles (Fig. 13 A) whose differentiation into vesicular follicles is described in an earlier chapter (p. 20). In opposition to this classic concept, Allen ( 1923) and others contend that the definitive ova do not represent grown primordial ones but that they are new cells proliferated periodically in the adult from the germinal (peritoneal) epithelium.
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Anomalies.  -  Congenital absence or duplication of the testes and ovaries is very rare. Fused testes and lobed ovaries are also known,
Teratomata .  -  These peculiar tumor-like growths occur rather frequently in the ovarv, less often in the testis and other regions. The simpler types, called dermoid cysts, contain such ectodermal derivatives as skin, hair, nails, teeth, and sebaceous glands. They grade into comple.Kes consisting of organ-like masses, from all three germ layers, intermingled without order. Misshapen representatives of all tissues and organs may be present. Among other explanations of the cause, the isolation and subsequent faulty development of blastomeres has been advanced.
Transformation of the Mesonephric Tubules and Ducts.  -  In both male and female embryos of 21 mm., the mesonephros has degenerated until only twenty-six tubules at most persist, and these are separated into a cranial and a caudal group. In the cranial group of 5 to 12 tubules, the collecting jiortions have broken apart from the secretory portions. The free ends of these collecting tubules project against that part of the inner epithelial mass which gives rise to the rete tubules of either testis or ovary (Figs. 149 and 151). The cords of the rete develop in contact with the collecting tubules of the mesonephros and unite with them in fetuses of 10 weeks.
In the male, the lumina of rete and collecting tubules become continuous and the cranial collecting group is transformed into the ductuli efcrentcs of the epididymis. During the fifth month of pregnancy the efferent ductules coil at their proximal ends, and, when surrounded by connective tissue, they are known as lobuli epididymidis. The lower group of collecting tubules persist as the vesitigial paradidymis and duciuli abherautes (Fig. 160 G). The efferent ductules convey spermatozoa from the testis tubules into the mesonephric duct, which thus becomes the male genital duct. The cranial portion of the mesonephric duct coils and forms the ductus epididymidis; its blind cranial end persists as the appendix epididymidis. The caudal portion of the male duct remains straight, and, as the ductus deferens and ejaculatory duct, extends from the epididymis to the urethra. Near its opening into the latter it dilates to form the ampulla, from the wall of which is evaginated the sacculated seminal vesicle in fetuses of three months (Fig. 143).
In the female, the rete ovaru is always vestigial, yet some time before birth it becomes tubular and unites with the cranial persisting group of mesonephric collecting tubules which forms a rudimentary structure, the epodphoron (Fig. 160 B). The caudal group of mesonephric tubules constitutes the paroophoron. Usually the greater part of the mesonephric ducts atrophy in the female, the process beginning early in the third month, but portions persist as Gartner - s ducts of the epodphoron.
Gartner - s ducts may extend as vestigial structures from the epodphoron to the lateral walls of the vagina, passing through the broad ligament and the wall of the uterus. They open into the vagina close to the free border of the hymen. The ducts are rarely present throughout their entire length and are absent in two-thirds to three-quarters of the cases examined.
Transformation of the Mullerian Ducts.  -  The Mullerian, or female ducts, follow the course of the mesonephric ducts (Fig. 148). At first lateral in position, the Mullerian ducts cross the mesonephric ducts and enter the genital cord median to them (Fig. 160 A). In embryos of two months their caudal ends are dorsal to the urogenital sinus and extend as far as the Mullerian tubercle, a projection into the median dorsal wall of the primitive urethra formed by the earlier entrance of the mesonephric ducts (Fig. 142). This tubercle marks also the position of the future hymen. In fetuses of u weeks the Mullerian ducts break through the wall of the urethra and open into its cavity. Before this takes place, their caudal ends, which are pressed close together between the mesonephric ducts in the genital cord, fuse, and in both male and female embryos of two months give rise to the single anlage of the uterus and vagina (Figs. 142 and 153 A). The paired cranial portions of the Mullerian ducts become the uterine tubes. During development, the ostial ends of the uterine tubes undergo a true descensus from the third thoracic to the fourth lumbar vertebra.
In the male, these parts are rudimentary. Those portions of the Mullerian ducts corresponding to the uterine tubes and uterus begin to degenerate at the beginning of the third month. The vaginal segment remains as a pouch on the dorsal wall of the urethra, the vagina masculina, or prostatic utricle (Fig. 143). The extreme cranial end of each Mullerian duct constitutes a so-called appendix testis (Fig. 160 C).
The Uterus and Vagina.  -  Since the Mullerian ducts develop in the urogenital folds, they make two bends in their course (Fig. 153 A) corresponding to those of the folds (p. 150). Each duct consists of a cranial longitudinal ])ortion, a middle transverse portion, and a caudal longitudinal jiortion which is fused with its fellow to form the utero-vaginal anlagc. At the angle between the cranial and middle segments is attached the inguinal Jold, the future round ligament of the uterus (Figs. 154 and 155). The mesenchyme condenses about the utero-vaginal anlage and the middle transverse portion of the Mullerian ducts, forming a thick, sharply defined layer, from which is differentiated later the muscle and connective tissue of these organs (Fig. 153 A). As development proceeds, the cranial wall between the transverse limbs of the Mullerian ducts bulges outward, so that its original cranial concavity becomes convex (Fig. 153 B). The middle, transverse portions of the ducts are thus taken up into the wall of the uterus to form its JunJus, while the narrow cervix of the uterus and the vagina arise from the original utero-vaginal anlage. A distinction between uterus and vagina is not evident until the middle of the fourth month. The entrance to the vagina is originally some distance above the outlet of the urogenital sinus (Fig. 160 A). This intervening stretch of sinus hereafter elongates relatively little and so becomes the shallow vestibule into which both urethra and vagina open (Fig. 160 B),
.
Fig. 153-  -  Diagrams illustrating the development of the uterus and vagina (Felix-Prentiss).
.
.
The lower limit of the vagina lies at the level of Muller - s tubercle, where the utero-vaginal anlage breaks through the wall of the urogenital sinus. The tubercle is compressed into a disc, lined internally by the vaginal epithelium and externally by the epithelium of the urogenital sinus, or future vestibule. These layers, with the mesenchyme between them, constitute the hymen, which thus guards the opening into the vagina (Fig. 160 A, B). A cireular aperture in the hymen is for a time closed by a knob of epithelial cells, but later, when the hymen becomes funnel-shaped, the opening is compressed laterally to form a sagittal slit.
.
Muller - s tubercle persists in the male as the colliculus seminalis, from the summit of which leads off the prostatic utricle.
At 10 weeks, the serosa, muscularis, and mucosa are indicated. The first circular muscle fibers appear during the fifth month; the other muscle layers develop later. The epithelium of the uterine tubes and corpus remains simple; that of the cervix and vagina becomes stratified at nine weeks. The tubular glands of the corpus appear about the seventh month. The uterus shortens greatly soon after birth and does not fully recoup this loss until the eleventh year. The virginal size is attained by a short period of rapid grovdh, chiefly before puberty. The vagina is for a time without a lumen, and solid epithelium fills its fornices. The vaginal lum.en reappears in fetuses of about five months through degeneration of the central epithelial cells.
.
Anomalies.  -  Many cases of abnormal uterus and vagina occur. The more common anomalies are: (i) Complete duplication of the uterus and vagina, due to the failure of the Mullerian ducts to fuse. (2) Uterus bicornis, due to the incomplete fusion of the ducts. Combined with these defects, the lumen of the uterus and vagina may fail, partly or completely, to develop and the vaginal canal may not open to the exterior (imperforate hymen) . (3) The body of the uterus may remain flat (uterus planifundus; Fig. 153 . 1 ) or fail to grow to normal size (uterus fetalis and infantalis). (4) Congenital absence of one or both uterine tubes, or of the uterus or vagina, rarely occurs, but may be associated with hermaphroditism of the external genitalia. The hymen is of variable shape.
.
Fig. 154.  -  Ventral dissection of the urogenital organs in a human embryo of two months (Prentiss). The right suprarenal gland has been removed to show the metanephros.
.
Ligaments of the Internal Genitalia.  -  Female.  -  The ovary is primarily suspended by a short mesentery, termed the mesovarium (Fig. 151). A further support is furnished by the terminal portion of the primitive genital fold, which unites the caudal end of the ovary first to the genital cord and then to the uterus that develops in it. This connection becomes fibrous and is known as the proper ligament of the ovary (Fig. 15 s). With the degeneration of the mesonephric system, the uterine tube lies in a fold, the mesosalpinx (Fig. 151).
The mutual fusion of the caudal portions of the urogenital folds, as the genital cord, forms a mesenchymal shelf bridging in the coronal plane between the two lateral body walls and containing the uterus in its center (Fig. 154). It persists as the sheet-like broad ligaments of the uterus.
In embryos of 14 mm., a band, called the inguinal fold, joins the urogenital fold to the inguinal crest, which is merely a prominence on the adjoining al)dominal wall (Fig. 154). Within the inguinal crest is differentiated the chorda gubcrnaculi, which later becomes fibrous. The abdominal muscles develop around it and form a tube, the inguinal canal. At the outer end of the canal the external obliciue muscle leaves a foramen, through which the chorda connects with a second cord that extends to the genital swelling and is hence designated the ligamentum labiale. The chorda gubernaculi and the ligamentum labiale thus form a continuous cable from the labium majus to the uterus, which in the meantime has been developing in the fused urogenital folds; the two together constitute the round ligament of the uterus (F'ig. 155).
.
.
Fig. 155.  -  Ventral dissection of the urogenital organs in a female fetus of nine weeks (Prentiss).
.
.Male.  -  The primitive mesentery of the testis is the mesorchium (Figs. 149 and 150). It is represented in the adult as the fold between the epididymis and testis. The degenerating cephalic end of the mesonephros for a time constitutes the so-called diaphragmatic ligament of the mesonephros (Figs. 154 and 155).
.
The ligamentum testis, like the ligamentum ovaru, develops in the lower end of the genital fold and extends from the caudal pole of the testis to the mesonephric fold at a point adjacent to the attachment of the bridgelike inguinal fold (cf. Fig. 155). As in the female, the inguinal fold connects with the chorda guhernaculi within the inguinal crest, and this in turn is continued by way of the liganieutum scroti to the integument of the scrotum. A cord differentiates in the mesonephric fold and unites the ligamentum testis to the chorda gubernaculum. Thus there is formed a continuous ligament, the gubernaculum testis, extending from the caudal end of the testis through the inguinal canal to the scrotal integument. The gubernaculum is composed of the ligamentum testis, a mesonephric cord, the chorda gubernaculi, and the ligamentum scroti. It is the homologue of the ovarian ligament plus the round ligament of the uterus, between which the uterus intervenes (Fig. 155).
Descent of the Testis and Ovary.  -  The original positions of the testis and ovary change during development. At first they are elongate structures, extending in the abdominal cavity from the diaphragm toward the pelvis (Fig. 144). Since their caudal ends continue to grow and enlarge while their cranial portions atrophy, there is a progressive, wave-like shifting of the glands caudad. Yet an actual internal descent by mass movement does not occur. When the process of growth and degeneration is complete, the caudal ends of the testes lie at the boundary line between the abdomen and pelvis, whereas the ovaries are located in the pelvis itself, a position which they retain. Owing to the rotation of the o\mry about its middle point as an axis, it takes up a transverse position. The ovary also rotates nearly 180° about the Mullerian duct as an axis, and thus comes to lie caudal to the uterine tube.
.
.
Fig. 156.  -  Diagrams illustrating the descent of the testis, p.v., Processus vaginalis: .v.,
obliterated vaginal sac.
In addition to its early apparent migration, the testes normally leave the abdominal cavity and descend bodily into the scrotum. At the beginning of the third month, while the testes are still fairly high in the abdomen, sac-like pockets appear in each side of the ventral abdominal wall. These are the anlages of the vaginal sacs, and during the fourth, fifth, and sixth fetal months the testes lie near them without change of position. Each processus {saccns) vaginalis evaginates over the pubis, through the inguinal canal, and into the scrotum (Fig. 156). During the seventh to ninth months the testes also descend rapidly along the same path (Fig. 157). Although the factors involved are not sufficiently understood, it is clear that the gubernaculum testis plays an important part. From the caudal pole of each testis the corresponding gubernaculum extends through the inguinal canal to the scrotal wall. During the seventh month the gubernaculum not only ceases growth but actually shortens one-half. The resultant relative and actual shortening serves to draw the testes into the scrotum (Fig. 157), where they usually are found by the ninth month, or at least before birth. It must be understood that the testis and gubernaculum are covered by the peritoneum before the descent begins; consequently the testis follows the gubernaculum along the inguinal canal dorsal to the peritoneum, and, when it reaches the scrotum, is invaginated into the processus vaginalis, but does not lie within the cavity of the coelomic extension (Fig. 156). The gubernaculum of a newborn is but one-fourth the length when descensus begins; after birth it atrophies almost completely within a few months after birth the narrow canal connecting the processus vaginalis with the abdominal cavity becomes solid and its epithelium is resorbed. The vaginal sac, now isolated, represents the tunica vaginalis of the testis. Its visceral layer is closely applied to the testis and its parietal layer forms the lining of the scrotal sac. The ductus deferens, and the spermatic vessels and nerves, are carried down into the scrotum with the testis and epididymis. They are surrounded by connective tissue and constitute the spermatic cord. Owing to the path taken by the testis, the ductus deferens loops over the ureter in the abdomen (Fig. 160 C).
.
.
.
Fig. 157.  -  Ventral dissection of a full-term fetus to demonstrate the relation of the descended testis to the processus vaginalis (partly after Kollmann and Corning). On the left the peritoneum is intact; on the right the peritoneum and its sacculation are opened and the testis is rotated 90°.
.
In the female, shallow peritoneal pockets, frequently persistent as the diverticula of Nuck, correspond to the vaginal sacs of the male. Rarely, a miOre or less complete descent of the ovary into the labium majus occurs. The interposition of the uterus between the ovarian and round ligaments is responsible for the normal retention of the ovaries in the abdomen (Fig. 155).
.
Anomalies.  -  At times, the testes remain in the abdomen, undescended, a condition known as cryptorchism and associated with sterility in man. In some mammals (whale; elephant) it is the normal condition. When the inguinal canals of man remain open, conditions are favorable for one type of inguinal hernia of the intestine. Open inguinal canals, with a periodic descent during the breeding season, occur normally in some animals (rodents; bats).
.
C. The External Genitalia
Recent investigation (Spaulding, 1921) proves that the external genitalia exhibit recognizable sex differences almost from their first appearance. In embryos of 8 mm., a rounded genital tubercle develops in the midline of the ventral body wall, between the umbilical cord and tail (Fig. 144). Its caudal slope bears the shallow urethral groove which is separated from the anal pit by a transverse ridge (Figs. 158 A and 159 A ) ; this ridge comprises the primitive perineum. The margins of the groove are slightly elevated as the urethral folds. Embryos of about 15 mm. show rupture of the urethral membrane in the floor of the groove, and the genital tubercle becomes more conical. Sex can now be recognized by the length of the urethral groove which in males extends from the base of the tubercle nearly to its apex (Fig. 158 A, B), whereas in females it is shorter and terminates some distance below the apex (Fig. 159 A, B)\ this diagnostic feature prevails until the definitive modelling begins.
At about 16 mm. (seven weeks) the genital tubercle has elongated into a somewhat cylindrical phallus, bearing at its tip the rounded glans which is set off by a constricted neck from the shaft-like body (Figs. 158 A and 159 A). On either side of the base of the phallus, and separated from it by a groove, are lateral, rounded ridges; these are the labioscrotal swellings, possibly represented much earlier by certain indefinite elevations.
.
Male.  - Embryos of ten weeks are at the beginning of the definitive stage. In the male, the edges of the urethral groove progressively fold together and thus transform the open urogenital sinus into the tubular urethra (Figs. 158 B, C and 142). The fused edges constitute the raphe (Fig. 158 D). The scrotal swellings shift caudad to their final position where each becomes a half of the scrotum, separated from its mate by the raphe and underlying septum scroti. In the meantime, the shaft of the penis elongates, and, by the fourteenth week, the urethra has closed as far as the glans. The urethra is then continued along an epithelial plate which represents a solid part of the original urethral anlage incompletely partitioning the glans; by splitting, the plate is first converted into a trough which promptly recloses into a tube that continues the urethra to the definitive opening at the tip of the glans. A cylindrical collar of the surface epithelium, incomplete on the anal side, grows deep into the end of the primitive glans. By the disappearance of the central cells of the epithelial downgrowth, an outer cylindrical mantle, the prepncumi, or foreskin, is formed about the spheroidal glans penis (cf. Fig. 86). Where the epithelial downgrowth is incomplete the glans and fore-skin remain connected by the frenulum prepucu. The coropora cavernosa penis arise as paired mesenchymal columns. The corpus cavernosuni urethra: results from the linking of similar, unpaired anlages, one in the glans the other in the shaft.
.
.
.
Fig. 158.  -  Stages in the development of the male external genitalia (redrawn after S]3aulding). . 1 , Nearly seven weeks (X 15); B, nearly eight weeks (X 12): C, ten weeks (X 8); D, twelve weeks ( X 8).
.
Fig. 159.  -  Stages in the development of the female external genitalia (redrawn after Spaulding). , 4 , Nearly seven weeks (X i8); B, nearly eight weeks (X 15); C, ten weeks (X u): twelve weeks (X 8).
.
Female.  -  Changes in the female are less profound, yet slower (Fig. 159). The phallus lags in development and becomes the clitoris, with its homologous glans clitoridis and prepucium. The shorter urethral groove never extends onto the glans, as in the male. It remains open as the vestibule. The urethral folds which flank the original groove constitute the labia nuiwra. The primitive labio-scrbtal swellings grow caudad and fuse in front of the anus as the posterior commissure (embryos of u weeks), while the original lateral portions enlarge into the labia majora; these parts now form a horse-shoe shaped rim, open toward the umbilicus. The mans pubis, which arises later, appears to develop independently.
Besides the sexual difference in the length of the urethral groove already mentioned, male embryos of more than 20 mm. are characterized by a phallus which stands at right angles to the body, whereas in the female it curves downward.
,
HOMOLOGIES OF INTERNAL AND EXTERNAL GENITALIA .
Male .
Indifferent stage .
Female .
TestiS
Rete testis.
.
Gonad.
.
Ovary
[Rete ovaru].
.
Ligamentum testis. Gubernaculum testis.
.
Primitive ligaments.
.
Ligamentum ovaru proprium. Lig. ovaru -|- Lig. teres.
.
Ductuli efferentes. Paradidymis.
.
Mesonephric collecting tubules. Cranial group.
.Caudal group.
.
Epobphoron.
.Paroophoron.
.
Appendix epididymidis Ductus epididymidis. Ductus deferens. Seminal vesicle. Ejaculatory duct.
.
Mesonephric duct.
.
Gartner - s duct.
.
(1) Appendix testis.
.(2)
(3) Utriculus prostaticus (Vagina masculina).
.
Mullerian duct.
.
(0 Uterine tube.
.( 2 ) Uterus.
.(3) Vagina.
.
Colliculus seminalis.
.
Muller - s tubercle.
.
Hymen.
.
(1) Prostatic and membranous urethra.
.(2) Cavernous urethra.
.(3) Prostate gland.
.(4) Bulbo-urethral glands.
.
Urogenital sinus.
.
(1) Urethra and vestibule.
.(2)
(3) Para-urethral ducts.
.(4) Vestibular glands.
.
Penis.
.Gians penis.
.Anal surface of penis.
.
Phallus.
.Gians.
.Lips of urethral groove.
.
Clitoris.
.Gians clitoridis. Labia minora.
.
Scrotum.
.
Labio-scrotal swellings.
.
Labia majora. Posterior commissure.
Epididymis .
.
Fig. 160.  -  Diagrams to show the development of male and female genital organs from a common type (after Thompson).
.
.
Anomalies.- If the lips of the slit-like urogenital opening on the under surface of the penis fail to fuse, hypospadias results. Rarely, there is a similar defect on the upper surface  -  epispadias; it is usually associated with vesico-abdominal fissure.
True hermaphroditism consists in the presence of both testis and ovary in the same invividual. It is of rare occurrence in birds and mammals, is not uncommon in the lower dertelirates, and is the normal condition in many invertebrates (worms; molluscs). In man there are five authentic cases with combined ovotestis and four cases with separate ovary and testis. The internal genitalia are faultily bisexual. The external genitalia show mixed male and female characteristics. The secondary sexual characters (beard, mamm^, voice, etc.) are usually intermediate, tending now one way, now the other.
.
False hermaphroditism is characterized by the presence of the genital glands of one sex in an individual whose secondary sexual characters and external or internal genitalia resemble those of the opposite sex. In masculine hermaphroditism, an individual possesses testes, often undescended, but the external genitals (by retarded development) and secondary characters are like thoSe of the female. In feminine hermaphroditism, ovaries are present, and sometimes descended, but the other sexual characters, such as enlarged clitoris or fused laldae, simulate the male. The cause of hermaphroditism is unknown.
.
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Arey LB. Developmental Anatomy. (1924) W.B. Saunders Company, Philadelphia.

   Developmental Anatomy 1924: 1 The Germ Cells and Fertilization | 2 Cleavage and the Origin of the Germ Layers | 3 Implantation and Fetal Membranes | 4 Age, Body Form and Growth Changes | 5 The Digestive System | 6 The Respiratory System | 7 The Mesenteries and Coelom | 8 The Urogenital System | 9 The Vascular System | 10 The Skeletal System | 11 The Muscular System | 12 The Integumentary System | 13 The Central Nervous System | 14 The Peripheral Nervous System | 15 The Sense Organs | C16 The Study of Chick Embryos | 17 The Study of Pig Embryos | Figures Leslie Arey.jpg
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Developmental Anatomy - A Text-Book And Laboratory Manual Of Embryology

By

Leslie Bleainerd Arey


Professor Of Anatomy At The Northwestern University Medical School, Chicago .


With 419 Illustrations Many In Color


Philadelphia And London, W. B. Saunders Company


1924

Copyright., 1924, by W. B. Saunders Company, Made in US.A .


Preface

This book has been prepared for the use of medical students and others whose interests center primarily on man and mammals. The emphasizing of structural rather than functional aspects of Embryology is reflected in the title; such presentation is consistent both with the practical demands of modern courses and with the meagre information existant as to the physiological factors in developmcnt.


The volume contains three sections. In the first i>art the early stages are treated comparatively and the fulCcourse of prenatal and postnatal development is outlined. The second section traces the origin and differentiation of the human organ-systems, grouped according to their germlayer derivations. The third division comprises a laboratory manual for the study of chick and pig embryos.


Many illustrations are from the earlier Prentiss-Arey text and discontinuous fragments of description have likewise been retained. Yet, in plan and content the work is essentially new. It is hoped that the developmental story has been told in an orderly and clear, but concise fashion, and that it records accurately the present state of the subject.


L. B. Arey.

Chicago, ill., September, 1924.

Contents

PART I. GENERAL DEVELOPMENT

Introduction

General Features of Development

Fundamental Conceptions

The Vertebrate Groups

Titles for Collateral Reading and Reference

Chapter I. - The Germ Cells and Fertilization

The Germ Cells

Spermatogenesis, Oogenesis and Maturation

Ovulation and Insemination

Fertilization

Heredity and Sex

Chapter II. - Cleavage and the Origin of the Germ Layers

Cleavage

The formation of Ectoderm and Entoderm (Gastrulation)

Origin of the Mesoderm, Notochord and Neural Tube

Chapter III. - Implantation and Fetal Membranes

The Fetal Membranes of Reptiles and Birds

The Fetal Membranes of Mammals

The Fetal Membranes of Man

Implantation and Early Mucosal Relations

The Decidual Membranes

The Placenta

Parturition

Chapter IV. - Age, Body Form and Growth Changes

Age, Size and Weight of Embryos

An Outline of Prenatal Development

The Establishment of External Form

Growth Changes


PART IV. ORGANOGENESIS

Entodermal Derivatives

Chapter V. - The Digestive System

The Mouth

The Pharynx

The Digestive Tube

The Liver

The Pancreas

Chapter VI. - The Respiratory System

The Larynx

The Trachea

The Lungs

MeSodermal Derivatives

Chapter VII. - The Mesenteries and Coelom


The Mesenteries

The Primitive Mesentery

Differentiation of the Dorsal Mesentery

Differentiation of the Ventral Mesentery

The Ccelom

The Primitive Coelom

The Septum TransveRsum

The Pleuro-pcricardial and Pleuro-peritoncal Membranes

The Pericardium and Diaphragm

Chapter VIII. - The Urogenital System

The Urinary Organs

The Pronephros

The Mesonephros

The Metanephros

Differentiation of the Cloaca

The Genital Organs

Indifferent Stage

Internal Sexual Transformations

The External Genitalia

Homologies of Internal and External Genitalia


Chapter IX. - The Vascular System

Origin of the Blood Vessels and Blood Cells

Hemopoiesis

Development of the Heart

The Primitive Vascular System

Development of the Arteries

Development of the Veins

Fetal Circulation and the Changes at Birth

The Lymphatic System

Chapter X. - The Skeletal System

Histogenesis of the Supporting Tissues

Connective Tissue

Cartilage

Bone

Morphogenesis of the Skeleton

The Axial Skeleton

The Appendicular Skeleton

Chapter XI. - The Muscular System

The Histogenesis of Muscle

Morphogenesis of the Muscles

Ectodermal Derivatives

Chapter XII. - The Integumentary System

The Skin

The Nails

The Hair

Sebaceous Glands

Sweat Glands

Mammary Glands

Chapter XIII. - The Central Nervous System

Histogenesis of the Nervous Tissues

Morphogenesis of the Central Nervous System

The Spinal Cord

The Brain

Chapter XIV. - The Peripheral Nervous System

The Spinal Nerves

The Cranial Nerves

The Sympathetic Nervous System

The Chromaffin Bodies and Suprarenal Gland

Chapter XV. - The Sense Organs

General Sensory Organs

The Gustatory Organ 292

The Nose

The Eye

The Ear


Part III. A LABORATORY MANUAL OF EAIBRYOLOGY


Chapter XVI. - The Study of Chick Embryos

The Unincubated Ovum and Embryos of the First Day

Embryo of Five Segments (Twenty-Three Hours)

Embryo of Seven Segments (Twenty-five Hours)

Embryo of Seventeen Segments (Thirty-eight Hours)

Embryo of Twenty-seven Segments (Two Days)

Embryos of Three to Four Days

Chapter XVII. - The Study of Pig Embryos

The Anatomy of a Six Mm. Pig Embryo

The Anatomy of Ten to Twelve Mm, Pig Embryos

The Anatomy of an Eighteen Mm. Pig Embryo

The Anatomy of a Thirty-five Mm. Pig Embryo

Methods for the Dissection of Pig Embryos


PART I. GENERAL DEVELOPMENT


INTRODUCTION


The Scope of Embryology. - Developmental anatomy, or embryology, traces the formative history of the individual from the origin of the germ cells to the adult condition. Although the most striking changes in human development occur while the young (called an embryo or fetus) is still inside its mother - s womb, yet development by no means ceases at birth. Birth is a mere incident which occurs when the new individual is sufficiently advanced to allow its transference from a protected riterine environment to one in the external world. Some vertebrates, like fishes and amphibia, are capable of an active and independent existence at very immature stages; these free-living larvee, as they are termed, then gradually progress to adults. The human newborn, although far more complete anatomically, is still utterly dependent for food and care: many years of infancy and childhood must elapse before it becomes self-maintaining in human society. During all this period, postnatal development continues. Birth, itself, initiates anatomical changes of profound influence on the body. Throughout the entire growth period, with its uneven but steadily slowing growth rate, come the completion of some organs and a gradual remoulding of the shape of the body and its parts. Only at the age of twenty-five are these progressive changes complete.


All vertebrate, or backboned, animals are organized upon a common anatomical plan, and even many of their structural details are comparable, though superficially disguised. vSimilarly, their fundamental mode of development is essentially identical. The minor variations that do occur are caused by such secondary modifying factors as the crowding yolkcontent of the egg or adaptations to development inside or outside the mother - s body. While the comparative viewpoint is indispensable for gaining a broad understanding of embryology, it has been of especial importance in supplying missing parts of the human developmental story and in interpreting many perplexing conditions. For, the earliest human embryos known are about two weeks old and have the three primary germ layers already formed. Even invertebrate material is highly useful for demonstrating such early stages as maturation, fertilization, cleavage, and the formation of blastula and gastrula.


The Value of Embryology. - A general conception of how man and other animals develop from a single cell by orderly and logical processes should share in the cultural background of every educated mind. To the medical student, embryology is of primary importance because it affords a comprehensive understanding of the intricacies and variations of human anatomy, and thus is essential to sound surgical training. It also explains many anomalies and 'monstrous - conditions, and the origin of certain tumors and other pathological changes in the tissues. Obstetrics is essentially applied embryology. From the theoretical side, it is the key with which we may unlock the secrets of heredity, the determination of sex, and, in part, of organic evolution.


Histoucal. - The science of modern embryology is comparatively new, originating with the use of the compound microscope and advancing with the improvement of microscopical technique. Aristotle (384-322 B. c.), however, centuries before the introduction of magnifying lenses had followed the general development of the chick, day by day. The popular belief that slime and decaying matter is capable of giving rise to living animals, as also asserted by Aristotle, was disproved by Redi (1668).

.A few years after Harvey and Malpighi had published their fundamental studies on the chick embryo, Leeuwenhoek reported the discovery of the human Sp ermatozoon by Ham in 1677 - At this period, it was believed either that fully formed animals existed in miniature in the egg, needing only the stimulus of the spermatozoon to initiate development, or that similarly preformed bodies, male and female, constituted the spermatozoa and that these merely enlarged within the ovum. According to this doctrine of preformation, all future generations were likewise encased, one inside the sex cells of the other, and serious computations were made as to the probable number of progeny (200 millon) thus present in the ovary of Mother Eve, at the exhaustion of which the human race would end! Dalenpatius ( 1699) and others even believed they had observed a minute human form in the spermatozoon (Fig. i).


The preformation theory was strongly combated by Wolff ( 175 9), who saw that the organs of the early chick embryo were differentiated gradually from unspecialized li ving substance. This theory, known as epi genesis, was proved correct wEen von Baer discQvered the mammalian ovurn in 1 827, and later demonstrated the germ-layer composition of all embryos.


Fig. I. - Human sperm cell containing a miniature organism, according to Hartsoeker (1694).


About twenty years after Schleiden and Schwann (1839) had shown the cell to be the structural unit of the organism, the ovum and spermatozoon were recognized as true cells. O. Hertwig , in was the first to observe and appreciate the events of fertilizat ion . Henceforth, all multicellular organisms were believed to develop each from a single fertilized ovum. This conception is expressed in the famous aphorism: - ornne_ vivum ex ovo . - Modern embryology , as an organized and definite science, began with Balfou r (1874 ), who reviewed, digested, and made accessible the earlier scattered facts. Throughout this period, the experimental method of investigation has been used increasingly; without it many structural and physiological aspects of development would remain unsolved.


GENERAL FEATURES OF DEVELOPMENT


A multicellular embryo results from the division of the fertilized ovum to form daughter cells. These are at first quite similar in structure, and, if separated, in some animals each may become a complete embryo (sea urchin; certain vertebrates). In general, the development of an embryo depends: (i) upon the multiplication of its cells by division; (2) upon the growth in size of the individual cells; (3) upon changes in their form and structure.


Cell Division. - All cells arise from pre-existing cells by division. There are two methods of cell division - amitosis and mitosis.


Amitosis. - Cells may divide directly by the simple fission of their nuclei and cytoplasm. This rather infrequent process is called amitosis. Amitosis is said by many to occur only in specialized or moribund cells. It is the type of cell division demonstrable in the epithelium of the bladder.


Mitosis - In the reproduction of typically active somatic cells and in all germ cells, complicated changes take place in the nucleus. These changes give rise to thread-like structures, hence the process is termed mitosis (thread) in distinction to amitosis (no threadk Mitosis is divided for convenience into four phases (Fig. 2) : Prophase. - 1. The centrosome divides and the two minute bodies resulting from the division move apart, ultimately occup^dng positions at opposite poles of the nucleus (I-uI).


2. Astral rays appear in the cytoplasm about each centriole. They radiate from it, and the threads of the central or achromatic spindle are formed between the two asters, thus constituting the amphiastcr (u).


3. The nuclear membrane and nucleolus disappear, the karyoplasm and cytoplasm becoming confluent.


4. During the above changes the chromatic network of the resting nucleus resolves itself into a skein, or spireme, which soon shortens and l;)reaks up into distinct, heavily-staining bodies, the chromosomes (u, uI). x\ definite number of chromosomes is always found in the cells of a given species, the chromosomes may be block-shaped, rod- shaped, or bent in the form of a U or V.


Fig. 2. - Diagrams of the phases of mitosis (Schafer).


5. The chromosomes arrange themselves in the equatorial plane of the central spindle (IV). If U- or V-shaped, the angle of each is directed toward a common center. The amphiaster and the chromosomes together constitute a mitotic figure, and at the end of the prophase this is called a monaster.


Metaphase. - The longitudinal splitting of the chromosomes into exactly similar halves constitutes the metaphasc (IV). The aim of mitosis is thus accomplished, an accurate division of the chromatin between the nuclei of the daughter cells.


Anaphase. - The two groups of daughter chromosomes separate and move up along the central spindle fibers, each toward one of the two asters. Hence this is called the diaster stage (V, VI). Each centriole may divide in preparation for the next diviSion of the daughter cells.

Telophase. - i. The daughter chromosomes resolve themselves into a reticulum and daughter nuclei are formed (Vu, VuI).


2. The cytoplasm divides in a plane perpendicular to the axis of the mitotic spindle (VuI). Two complete daughter cells have thus arisen from the mother cell.

The number of chromosomes is constant in the cells of a given species. The smallest assortment, two, occurs in Ascaris megalocephala univaleus, a round worm parasitic in the intestine of the horse. The largest number known is found in the brine shrimp, Artemia, where 1 68 have been counted. The chromosome enumeration for the human cell has been variously stated but the results of Winiwarter (1912), Grosser (1921 ), and Painter (1923) now agree on a relatively high number, which Painter establishes as 48 for whites and negroes of both sexes.


The Germ Layers. - The first changes in the form and arrangement of the cells establish three definite plates, the primary germ layers, which are termed from their positions the ectoderm (outer skin), mesoderm (middle skin) and entoderm (inner skin) (Fig. 4). Since the ectoderm covers the body, it is primarily protective in function, but it also gives origin to the nervous system, through which sensations are received from the outer world. The entoderm, on the other hand, lines the digestive canal and is from the first nutritive. The mesoderm, lying between the other two layers, naturally performs the functions of circulation, of muscular movement, and of excretion; it also gives rise to the skeletal structures which support the body. While all three germ layers form definite sheets of cells known as epithelia, the mesoderm takes also the form of a diffuse meshwork of cells, the mesenchyme (Fig. 3).


Fig. 3. - Alesenchyme from a chick embryo (Prentiss). X 495.


The cells of these layers are modified in turn to form tissues, such as muscle and nerve, of which the various organs are composed. The organs, associated as organ systenis, constitute the organism, or body, that of adult man containing 2 5 million million red blood cells alone. In every organ, one tissue, like the epithelial lining of the stomach, is predominately important; the others are accessory.


Histogenesis. -The cells of the germ layers are at first alike in structure. Thus, the evagination which forms the primordial arm is composed of a single layer of similar ectodermal cells, surrounding a central mass of diffuse mesenchyme (Fig. 406). Gradually the ectodermal cells multiply, change their form and structure, and give rise to the layers of the epidermis. By more profound structural changes the mesenchymal cells ahso are transformed into the elements of connective tissue, tendon, cartilage, bone, and muscle - aggregations of modified cells which are termed tissues. The development of modified tissue cells from the undifferentiated cells of the germ layers is known as histogenesis.


During histogenesis, the structure and form of each tissue cell are adapted to the ])erformance of some special function or functions. Cells which have once taken on the structure and functions of a given tissue cannot give rise to cells of any other type. In tissues like the epidermis, certain cells retain their ])rimitive embryonic characters throughout life, and, by continued cell division produce new layers of cells which are later specialized. In other tissues all of the cells are differentiated into the adult type, after which no new cells are formed: this takes place in the nervous elements of the central nervous system. Contrariwise, most tissue cells are undergoing retrogressive changes throughout life. In this way, the cells of certain organs like the thymus gland and mesonephros degenerate and largely disappear. The cells of the hairs and the surface layer of the epidermis become cornified and eventually are shed. Thus, normally, many tissue cells are continually being destroyed and replaced by new cells.


This series of changes - an embryonic (undifferentiated) stage; progressive functional s])ecialization ; gradual degeneration; death and removal - which tissue cells experience is designated by the term cytomorphosis.

Derivatives of the Germ Layers. - The tissues of the adult are derived from the primary germ layers as follows: .


Ectoderm

Mesoder


Entoderm Epithelium of: I. Pharynx and derivatives. Auditory tube.

Tonsils.

Thymus.

Thyroid.


I. Epidermis and derivatives. Hair; nails; glands.

Lens of eye.

A. Mesothelium.

1. Pericardium.

2. Pleura.

3. Peritoneum.

4. LTrogenital epithelia.

5. Striated muscle.


2. Epithelium of:

Organs of special sense. Cornea.


Ectoderm


Mesoderm


Entoderm


Mouth; enamel organ. Oral glands; hypophysis. Anus.

Amnion; chorion.


B. Mesenchyme.


Parathyroid.

2. Respiratory tract.


1 . Smooth muscle.

2. Notochord.

3. Connective tissue; .


Lungs.

3. Digestive tract.

Larynx; trachea.

3. Nervous tissue. Neuroglia. Chromaffin tissue.


cartilage; bone.

4. Blood; bone marrow.

5. Endothelium of blood .


Yolk sac; allantois.

4. Bladder (except trigone).

5. LTrethra (except prostatic).

6. Prostate.

Liver; pancreas.

4. Smooth muscle of; Iris.

Sweat glands.

vessels and lymphatics.

6. Lymphoid organs.

7. Suprarenal corte.



Primitive Segments - Metamerism. - A prominent feature of vertebrate embryos are the primitive segments, or metameres (Fig. 59). These segments are homologous to the serial divisions of an adult earth-worm - s body, divisions which, in the earth worm, are identical in structure, each containing a ganglion of the nerve cord, a muscle segment, or myotome, and pairs of blood vessels and nerves. In vertebrate embryos, the block like primitive segments lie next the neural tube and are known as mesodermal segments, or somites (Fig. 4). Each pair gives rise to a vertebra, to two myotomes, or muscle segments, and to paired vessels; each set of mesodermal segments is supplied by a pair of spinal nerves: consequently, the adult vertebrate body is segmented like that of the earth worm. As a worm grows by the formation of new segments at its tail-end, so the metameres of the vertebrate embryo begin to form in the head and are added tailward. There is this difference between the segments of the worm and the vertebrate embryo; the segmentation of the worm is complete, while that of the vertebrate is incomplete ventrally.


Fig. 4. - Diagrammatic transverse section of a vertebrate embryo (Minot-Prentiss).


Somatopleure and Splanchnopleure. In early embryos the mesoderm splits into two layers, the somatic (dorsal) and splanchnic (ventral) mesoderm (Fig. 4). The ectoderm and somatic mesoderm constitute the lu)dy wall, which is termed the somatopleure. In the same way, the entoderm and splanchnic mesoderm combine as the splanchnopleure; it forms the mesenteries and the walls of the gut, heart, and lungs.


Coelom. -The space between the somatopleure and splanchnopleure is the ccclom, or body cavity. At the first splitting of the mesoderm, isolated clefts are produced. These unite on each side and eventually form one cavity - the coelom. With the extension of the mesoderm, the cot'lom surrounds the heart and gut ventrally (Fig. 4). Later, it is subdivided into the pericardial caznty about the heart, the pleural cavity of the thorax, and the peritoneal cavity of the abdominal region. The ci)ithelia lining the several body cavities are termed mesothelia.


The Nephrotome. - The bridge of cells connecting the primitive segment with the unsegmented somatic and splanchnic layers is the nephrotome, or intermediate cell mass (Fig. 4). From these will develop the urogenital glands and ducts.


D evelopmental Processes. - The developing embryo exhibits a ])rogressively comjilex structure, the various steps in the production of which occur in orderly sequence. There may be recognized in development a number of component mechanical processes which are used repeatedly by the embryo. The general and fundamental process conditioning ilifferentiation is cell multiplication, and the subsequent growth of the daughter cells. The more important of the specific developmental ])rocesses are the following: ( i) cell migration; (2) localized growth, resulting in eidargements and constrictions; (3) cell aggregation, forming (a) cords, (b) sheets, [c] masses; (4) delamination, that is, the splitting of single sheets into separate layers; (5) folds, including circumscribed folds which produce ia) evaginations, or out-pocketings, (b) invaginations, or in-pocketings.


The production of folds, including evaginations and invaginations, due to unequal rapidity of growth, is the chief factor in moulding the organs and hence the general form of the embryo.


FUNDAMENTAL CONCEPTIONS

The Anlage. - This German word, which lacks an entirely satisfactory English equivalent, is a term applied to the first discernible cell, or aggregation of cells, which is destined to form any distinct jiart or organ of the embryo. In the broad sense, the fertilized ovum is the anlage of the entire adult organism; furthermore, in the early cleavage stages of certain embryos it is possible to recognize single cells or cell groups from which definite structures will indubitably arise. The term anlage, however, is more commonly applied to the primordia that differentiate from the various germ layers. Thus the epithelial thickening over the optic vesicle is the anlage of the lens.


The Law of Genetic Restriction. - As development advances, there is a constantly increasing restriction in the kind of differentiation open to the various parts. Each emerging tissue or organ is more rigidly bound to its particular type of differentiation than was the generalized material from which it came. A line of specialization, once begun, cannot be abandoned for another type. The parent tissue, likewise, is limited by losing the capacity for duplicating anlages already formed. Thus, the primitive thyroid can never become anything but a thyroid, whereas the gut that formed it also buds off, at other levels, the lungs, liver, and pancreas. Yet if the embryonic thyroid were destroyed, the pharynx would never replace it. From mesenchyme arise connective tissue, blood cells, and smooth muscle; when once the specialization begins, there can be no retraction or transformation to another type.


Continuity of the Germ Plasm. - According to this important conception of Weismann, the body-protoplasm, or soma, and the reproductive-protoplasm differ fundamentally. The germinal material is a legacy that has existed since the beginning of life, from which representative portions are passed on intact from one generation to the next. Around this germ plasm there develops in each successive generation a shortlived body, or soma, which serves as a vehicle for insuring its transmission and perpetuation. The reason, therefore, why offspring resembles parent is because each develops from portions of the same stuff.


The Law of Biogenesis - Of great theoretical interest is the fact, constantly observed in studying, embryos, that the individual in its development repeats hastily and incompletely the evolutionary history of its own species. This law of recapitulation was first stated clearly by Muller in 1863, and was termed by Haeckel the law of biogenesis. In accordance with it, the fertilized ovum is compared to a unicellular organism like the Ameba: the blastula is supposed to represent an adult Volvox type; the gastrula, a simple sponge; the segmented embryo, a worm-like stage ; and the embryo with gill slits may be regarded as a fishlike stage. Moreover, the blood of the human embryo in development passes through stages in which its corpuscles resemble in structure those of the fish and reptile; the heart is at first tubular, like that of the fish, and the arrangement of blood vessels is equally primitive; the kidney of the embryo is like that of the amphibian, as are also the genital ducts. Many other examples of this law may readily be observed.


Some apparently useless structures appear during development, perfunctorily reminiscent of ancestral conditions; certain other parts, of use to the embryo alone, are later replaced by better-adapted, permanent organs. Representatives of either type may eventually disappear or they may persist throughout life as rudimentary organs; more than a hundred of the latter have been listed for man. Still other ancestral organs abandon their provisional embryonic function, yet are retained in the adult and utilized for new purposes.


THE VERTEBRATE GROUPS

There are five vertebrate classes, the higher characterized by the possession of an enveloping embryonic membrane, called the amnion, and another embryonic appendage, known as the allantois:

(R) Anamniota (amnion absent).

1. Fishes - lamprey; sturgeon; shark; bony fishes; lung fish.

2. Amphibia - ^salamander; frog; toad; etc.

{B) Amniota (amnion present).

3. Reptiles - lizard; crocodile; snake; turtle.

4. Birds.

5. hlammals. Characterized by hair and mammary glands, (a) Monotremes - duck-bill; primitive mammals that have a cloaca and lay eggs with shells.


(C) Marsupials - oppossum; kangaroo; etc. The young are born immature and are sheltered in an integumentary pouch, (r)Placentalia. All other mammals whose young are nourished in the uterus by a placenta.

Ungulate series. Hoofed mammals (cattle; sheep; pig; deer; horse; etc.).

Unguiculate series. Clawed mammals (mole; bat; rat; rabbit; cat; dog; etc.). The highest order is the Primates (lemur; monkey; ape, man).

The Vertebrate Body Plan. - All vertebrate animals are constructed in accordance with a common body plan. The distinctive characteristics of the vertebrate type include: .

1. A tubular central nervous system, dorsally placed (Fig. 4).

2. A notochord, between the neural tube and gut (Fig. 4). This cellular |3rimitive-axis is replaced, wholly or in part, by the vertebral column.

3. A pharynx, which develops paired pouches and clefts that determine the positions of important nerves, muscles and blood vessels (Fig. 91).

4. The position of the mouth. Unlike the condition in many invertebrates, it is not surrounded by a circumoral ring of nervous tissue which connects a dorsal - brain - with a ventral chain of ganglia.

5. The limbs. Two pairs, with an internal skeleton (Fig. 227).

6. A coelom, which is divided into a dorsal, segmental part (cavities of the somites), and a ventral, unsegmented part, partitioned by the septum transversum (diaphragm) into thoracic and abdominal portions (Fig. 4 • .


TITLES FOR COLLATERAL READING AND REFERENCE

Broman. Normale und abnorme Entwicklung des Menschen.

Corning. Entwicklungsgeschichte des Menschen.

Duval. Atlas D - Embryologie.

Hertwig. Handbuch der Entwicklungslehre der Wirbeltiere.

Keibel and Mall. Human Embryology.

Kellicott. A Textbook of General Embryology.

Kollmann. Handatlas der Entwicklungsgeschichte des Menschen.

Lillie. The Development of the Chick.

Minot. A Laboratory Text-book of Embryology.

McMurrich. The Development of the Human Body.

Patten. The Early Embryology of the Chick.

Wilson. The Cell in Development and Inheritance.



CHAPTER I . THE GERM CELLS AND FERTILIZATION THE GERM CELLS .


All multicellulai' animals, except a few invertebrates, result from the union of two ripe sex cells. These are re])resentative portions of the germ plasm stored in the male and female sex glands, and are termed spermatozoon and ovinn respectively. In form and function they are quite unlike, for each is adapted to a specific purpose. It will be simplest first to describe these elements fully-formed, and then to show how they develop, mature, meet, and unite.


The Ovum. - The female germ cell, or ovum, is a typical animal cell produced in the ovary. Although always large, its exact size is correlated with the amount of stored food substance. The smallest eggs are those of the mouse and deer (about 0.07 mm.). The largest have a diameter measurable in inches (birds; a shark). Most ova are nearly spherical in form and posSess a nucleus with nucleolus, chromatin network, and nuclear membrane (Figs. 5 and 7). The nucleus is essential to the life, growth, and reproduction of the cell. The function of the nucleolus is unknown; the chromatin bears the hereditary qualities. The cytoplasm is distinctly granular and contains more or less numerous yolk granules, mitochondria, and rarely a minute centrosome.


Fig. 5. - Ovum of monkey (Prentiss). X 430.


The yolk, or deutoplasm, containing a fatty substance termed lecithin, furnishes nutriment for the developing embryo. It is doubtful if any ovum is totally devoid of yolk, yet it is useful as a basis for classifying eggs. Those ova which contain relatively little yolk, uniformly distributed, are termed isolecithal. Examples are found among various invertebrates and in all placental mammals, for such embryos either attain an independent existence quickly or are sheltered and nourished within the uterine wall of the mother. If the yolk collects at one end (called the vcgdal pole in contrast to the more jmrely jirotoplasmic animal pole) the ova are said to he telolecuhal. Many invertebrates and all vertebrates lower than the Placentalia illustrate this type. The so-called yolk of the hen - s egg (Fig. 6) is the ovum proper and its yellow color is due to the large amount of lecithin it contains. Finally, among the arthropods the yolk is centrally located and surrounded by a peripheral shell of clear cytoplasm; such eggs are centrolccithal.



Fig. 6. - Diagrammatic longitudinal section of a hen - s egg (Thomson in Heisler).


Fig. 7. - . 4 , Human ovum, approaching maturity, examined fresh in the liquor folliculi (Waldeyer). X 415. The zona pellucida appears as a clear girdle surrounded by the cells of the corona radiata. Yolk granules in the cytoplasm enclose the nucleus and nucleolus. 5 , A human spermatozoon correspondingly enlarged.


Most ova become enclosed within protective membranes, or envelopes. The vitelline membrane, secreted by the egg itself, is a primary membrane (Fig. 5). The follicle cells about the ovum usually furnish other secondary membranes, such as the zona pellucida. In lower vertebrates tertiary membranes may be added as the egg passes through the oviduct and uterus ; the albumen and shell of the hen - s egg (Fig. 6) or the jelly of the frog - s egg are of this sort.


The Human Ovum. - This is relatively of small size, measuring about 0.2 mm. in diameter (Fig. 7). It conforms closely to the isolecithal mammalian type, but has fine yolk granules somewhat condensed centrally. There is apparently a very delicate vitelline membrane, and outside it a thick, radially-striate membrane, the zona pellucida. The striate appearance is said to be due to fine canals through which nutriment is transferred from smaller follicle cells during the growth of the ovum within the ovary.


The Spermatozoon. - -In a few instances only, does the mature male element, or spermatozoon, resemble a typical cell. Most are slender, elongate structures which develop a flagellum to accomplish the active swimming that characterizes the cell. Unlike the ovum, which is the largest cell of an organism, the spermatozoon is usually the smallest. The extremes of size range from 0.018 mm. in Amphioxus to 2.0 mm. in an amphibian. The commonest shape is that of an elongate tadpole, with an enlarged head, short neck (and connecting piece), and thread-like tail (Fig. 8).


Fig. 8. - .1, Diagram of a human spermatozoon, surface view (Meves). B, Human spermatozoa, from life, in edge and surface view. X 700.


The Human Spermatozoon. - The sperm of man is of average size (0.055 mm.) and shape (Fig. 8). Compared to the ovum its volume is as i : 200,000 (Fig. 7). The /zcah is about 0.005 mm. in length. It appears oval in surface view, pear-shaped in profile. When stained, the anterior two-thirds of the^head may be seen to constitute a cap, and the sharp border of this cap is the so-called perforatorium. The head contains the nuclear elements of the sperm cell. The disc-shaped neck includes the anterior centrosonial body. The tail begins with the posterior centrosonial body and is divided into a short connecting piece, a chief piece, or flagellum, which forms about four-fifths of the length of the sperm cell, and a short end piece, or terminal filament. The connecting piece is marked off from the chief piece by the annulus. The connecting piece is traversed by the axial filament {fdvLm principale), and is surrounded: (i) by the sheath common to it and to the flagellum; (2) by a sheath containing a spiral filament; and (3) by a mitochondrial sheath. The chief piece is composed of the axial filament, surrounded by a cytoplasmic sheath, while the end piece comprises the naked continuation of the axial filament.


Atypical spermatozoa occur in some individuals. These include giant and dwarf forms, and elements with multiple heads or tails.


Comparison of the Ovum and Spermatozoon. - The dissimilar male and female sexual cells are admirably adapted to their respective functions, and illustrate nicely the modifications that accompany a physiological division of labor. Each has the same amount of chromatin, although in the sperm it is more compactly stored. The cells thus participate equally in heredity. The egg contains an abundance of cytoplasm (but nO' centrosome), and often a still greater supply of stored food. As a result, it is large and passive, yet closely approximates the typical cell. On the contrary, the sperm is small, and at casual inspection bears slight resemblance to an ordinary cell. Its cytoplasm is reduced to a bare minimum and contains no deutoplasm. Structurally, all is subordinated to a motile existence. Correlated with small size is an extraordinary increase in numbers, for the greater the total liberated the more surely will the ovum be found. Hence, apart from its role in heredity, the chief function of the spermatozoon is to seek the ovum and activate it to divide.

SPERMATOGENESIS, OOGENESIS AND MATURATION


In becoming specialized germ cells, the ovum and spermatozoon pass through parallel stages. The general process of sperm formation is designated spermatogenesis; that of egg formation, oogenesis. An essential feature of lioth is a component process, termed maturation, which is important for the following reason. Since reproduction in vertebrates depends upon the union of male and female germ cells, it is manifest that without special provision this union would necessarily double the number of chromosomes at each generation. Such progressive increase is prevented by the events of maturation. This may be defined as a form of cell division during which the number of chromosomes in the germ cells is reduced to one-half the number characteristic for the species. Its significance in the mechanism of inheritance is discussed on p. 28.


Spermatogenesis. - The spermatozoa originate in the epithelial lining of the testis tubules. Two types of cells are recognizable : the sustentacular cells (of Sertoli), and the male germ cells (Fig. 9). All the latter are descendants of primordial germ cells, which, by division, first form spermatogonia. These in turn |3roliferate and produce numerous generations of like cells. Ultimately the spermatogonia enter a growth period, at the end of which they are termed primary spermatocytes. Each contains the full number of chromosomes typical for the male of the species. Next ensues the process of maturation. This comprises two cell divisions, each primary spermatocyte producing two secondary spermatocytes, and these in turn four cells known as spermatids. During these cell divisions the number of chromosomes is reduced to half the original number in the spermatogonia.



Fig. 9. - Stages in the spermatogenesis of man arranged in a composite to represent a portion of a seminiferous tubule sectioned transversely. X 900.


The spermatids now attach to Sertoli cells, from which they appear to receive nutriment, and become transformed into mature spermatozoa (Fig. 10). The nucleus forms almost all the head; the centrosome divides, the resulting particles passing to the extremities of the neck. The posterior centrosome differentiates the annulus and is prolonged to become the axial filament. The cytoplasm forms the sheaths of the neck and tail, whereas the spiral filament of the connecting piece is derived from cytoplasmic mitochondria. When the transformation is complete, the spermatozoa detach from the sustentacular cells and are set free in the lumen of the seminiferous tubule.


Maturation in Ascaris. - The way the number of chromosomes is reduced may be seen in the spermatogenesis of Ascaris (Fig. 1 1). Four chromosomes are typical for Ascaris megalocephala hivalens, and each spermatogonical cell contains this number. In the early prophase of the primary spermatocyte there appears a spireme thread consisting of four parallel rows of granules (B). This thread breaks in two and forms two quadruple structures, known as tetrads (D-F) ; each is equivalent to two original chromosomes, paired side by side and split lengthwdse to make a bundle of four. At the metaphase {G}, a tetrad divides into its two original chromosomes which already show evidence of longitudinal fission and are termed dyads. One pair of dyads goes to each of the daughter cells, or secondary spermatocytes (G-I). Without the formation of a nuclear membrane, the second maturation spindle appears at once, the two dyads split into four monads, and each daughter spermatid receives two single chromosomes (monads), or one-half the number characteristic for the species. The tetrad, therefore, represents a precocious division of the chromosomes in preparation for two rapidly succeeding cell divisions which occur without the intervention of the customary resting periods. The easily understood tetrads are not formed in most animals, although the outcome of maturation is identical in either case. A diagram of maturation is shown in Fig. 12. The first maturation division in Ascaris is probably reductional, each daughter.



Fig. 10. Diagrams of the development of spermatozoa (Meves in Lewis and Stohr). a.c, Anterior centrosome; a.f., axial filament; c.p., connecting piece; ch.p., chief piece; g.c., cap; «., nucleus; nk., neck; p., cytoplasm; p.c., posterior centrosome.


Fig. 11. - Reduction of chromosomes in the spermatogenesis of Ascaris megalocephala bivalens (Brauer in Wilsonj. X about i loo. A-G, Successive stages in the division of the primary spermatocyte. The original reticulum undergoes a very early division of the chromatin granules which then form a quadruply split spireme (B, in profile). This becomes shorter (C, in profile), and then breaks in two to form two tetrads (D, in profile), (E, on end). F, G, H, first division to form two secondary spermatocytes, each receiving two dyads. I, Secondary spermatocyte. J, K, The same dividing. L, Two resulting spermatids, each containing two monads or chromosomes.


nucleus receiving two complete chromosomes of the original four, whereas in the second maturation division, as in ordinary mitosis, each daughter nucleus receives a half of each of the two chromosomes, these being split lengthwise. The latter division is equauonal and the daughter nuceli receive chromosomes bearing similar hereditary qualities.

Some animals reverse the sequence of events, reduction occurring at the second maturation division.


Maturation in Man - All spermatogonia, like the somatic cells, contain 48 chromosomes. The primary spermatocytes form tetrads and their division separates the mated chromosomal pairs into 24 single chromosomes of the secondary spermatocyte. Hence, this mitosis is reductional. The secondary spermatocytes then divide equationally into spermatids, each of which also contains 24 single chromosomes. Transformation into spermatozoa ensues (Figs. 9 and 10). Those details of maturation which pertain to sex determination are explained on p. 29.



Fig. 12. - Diagrams of maturation in spermatogenesis and oogenesis (Boveri).


Oogeneiss. - The ova, like the male elements, arise from the multiplication of primordial germ cells in the ovary (cf. p. 156). At birth, or shortly after, human ova cease forming. The number at this time in both ovaries has been placed between 100,000 and 800,000. Cellular degeneration reduces this supply until, at 18 years, the total is from 35,000 to 70,000 and several years after the menopause no more are to be found.


Late in fetal life, indifferent cells, by surrounding the young ova ioogonia) of the cortex, produce primordial follicles (Fig. 13 A). Some begin growth at once, others are quiescent until childhood or adult life is attained. During the slow growth period, the small, nutritive follicle cells increase in number and the oogonium gains greatly in size. When the follicle cells are several layers deep, a cavity appears between them. This enlarges, and there reSults a sac, the vesicular, or Graafian follicle, filled with fluid, the liquor folliculli (Fig. 13 5 ). As growth continues, the oogonium becomes located more and more eccentrically until it lies at one side of the follicle, buried in a mound of follicular cells termed the cumulus odphorus (egg-bearing hillock) (Fig. 14). Around the stratified follicle cells, now designated the stratum granulosum, there is differentiated from the stroma of the ovary the theca folliculi. This is composed of an inner, vascular tunica interna, and an outer, fibrous and muscular tunica externa.



Fig. 13. A, Two primordial human follicles and one early in growth (De Lee). X200. B, Section of a human ovarian cortex with ten primordial follicles and one young Graafian follicle (Piersol). X 90.


.At the end of the growth period, the follicle has enlarged from a structure 0.04 to 0.06 mm. in diameter to one 5 to 12 mm. (Fig. 16 A); similarly, the primordial ovum measured 0.04 to 0.05 mm. whereas it now has a diameter of about 0.2 mm. In harmony with the terminology for the male cell, the grown oogonium is designated a primary oocyte. The final stages of oogenesis are maturative. As in spermatogenesis, two cell divisions take place, but with this difference: the cytoplasm is divided unequally, and instead of four cells of equal size resulting, there are formed one large ripe ovum, or ootid, and three rudimentary or abortive ova, known as polar bodies, or polocytes (Fig. 15). The number of chromosomes is reduced in the same manner as in the male, so that the ripe ovum and each polar cell contain one-half the number of chromosomes found in the oogonium or primary oocyte.


Fig. 14. - An advanced Graafian follicle and ovum from a girl of fifteen (Prentiss). X 30.


Fig. 15. - . 4 , Formation of the first polar cell in the mouse ovum (Sobotta). X 1500. B, Separation of the second polar cell in the bat ovum (after Van der Stricht).


During maturation the ovum and first polocyte are termed secondary oocytes (comparable to secondary spermatocytes) ; the mature ovum (ootid) and second polocyte, with the daughter cells of the first polocyte. are comparable to the spermatids (Fig. 12). Each spermatid, however may form a mature spermatozoon, but only one of the four daughter cells of the primary oocyte becomes functional. The ovum develops at the ex])ense of the three ])olocytes which are abortive and degenerate eventually, though it has been shown that in some insects the polar cell may be fertilized and segment several times like a normal ovum. In most animals, the actual division of the first polocyte into two daughter cells is suppressed (cf. Fig. 1 5 B). The nucleus of the ovum after maturation is known as the jcniale pronndcus.


Maturation in the Mouse. - Typical maturation occurs in the mouse. 1 'he first jiolocyte is formed while the ovum is still in the Graafian follicle. Neither astral rays nor typical centrosomes have been observed; the chromosomes are V-shaped. The finst polar cell is constricted from the ovum and lies beneath the zona pellucida as a spherical mass about 25 micra in diameter (Fig. 15 A). Both ovum and polar cell (secondary oocytes) contain 20 chromosomes, or half the number normal for the mouse. The first maturation division is the reductional one and the chromosomes take the form of tetrads.


After ovulation has taken place, the ovum lies in the ampulla of the uterine tube. If fertilization occurs, a second polocyte is cut off, the nucleus of the ovum not having regained its membrane between the production of the first and second polar bodies (Figs. 15 A and 17 A, D). The second maturation spindle and second polar cell are smaller than the first. Immediately after the appearance of the second polar cell, the chromosomes resolve themselves into a reticulum and the female pronucleus is complete [Mig. 17 D).


Maturation in Man. - -The only observations are those of Thompson (1919), who believes to have identified stages in the formation of all three polar cells prior to ovulation or fertilization. The evidence presented, however, can hardly be accepted as conclusive. Yet, in Tarsius, a low primate, both polar cells have been observed.


OVULATION AND INSEMINATION

The ripe germinal products are next released from their respective sex glands and then brought together.

Ovulation. - The discharge of the ovum from its follicle comprises ovulation. A few animals breed continuously, but commonly there is a seasonal or annual spawning period. The several mammalian groups show various gradations between an almost continuous breeding period (oestrus) and an annual one. In man ovulation is periodic, at intervals of four weeks, beginning at puberty and ending with the menopause. However, fully formed Graafian follicles appear in the ovary during the second year of infancy, and, in some individuals, even before birth.


Ovulation may occur at this time, but usually these precociously formed follicles degenerate with their contained ova. Generally, only one follicle and ovum mature each month, the ovaries roughly alternating. Yet, ordinary multiple births depend on the rupture of two or more follicles. Rarely in man, but frequently in the monkey, follicles contain more than one egg. Thus, from the thousands of potential ova, only about 200 ripen in each ovary during the 30 years of sexual activity.


The completed follicle is from 5 to 12 mm. in diameter. It makes a bud-like protuberance from the surface of the ovary, and at this point the ovarian wall is very thin (Fig. 16 A). Internally, the follicle contains fluid, probably under vascular and muscular tension. The precise factors which cause rupture are not positively known, but they doubtless include mechanical pressure, perhaps combined with a weakening of the follicular wall by the digestive influence of the contained fluid (Schochet, 1920).


Fig. 16. A , Human uterine tube and ovary with mature Graafian follicle] (RibemontDessaignes). B, Sectioned human ovary with a corpus luteum verum and two corpora albicantia. X 1.5.


When the follicle bursts, the fluid gushes out, carrying with it the ovum torn loose from its cumulus oophorus. The adhering follicular cells, immediately investing the ovum, constitute the corona radiata (Fig. 6). The ovum is swept into the uterine tube by inwardly stroking cilia of the tubal Ambriae. Although the ovum is now ready to be fertilized, it is not yet technically - mature, - for the last polar division awaits the stimulus of fertilization.


The Corpus Luteum - After ovulation, a blood clot, the corpus liemorrhagicum, forms within the empty follicle. The follicle cells of the stratum granulosum proliferate, enlarge, and produce a yellow pigment. The w'hole structure, composed of lutein cells and connective-tissue strands, is termed the corpus luteum, or yellow body (Fig. 16 B). If pregnancy does not supervene, the corpus luteum spurium reaches its greatest development within two weeks and then gradually is replaced by fibrous tissue ; the resultant white scar is known as the corpus albicans. In pregnancy the corpus /zhtvuKuer/oH continues its growth until, at the thirteenth week, it reaches a maximal diameter of 1 5 to 30 mm. ; at term it is still a prominent structure in the ovary. The corpus luteum is believed to produce an important internal secretion, for if removed the ovum fails to attach to the wall of the uterus, or if the ovum is already embedded, development ceases (Fraenkel). An influence in retarding ovulation and stimulating the mammary gland function has also been shown experimentally (L. Loeb; O - Donoghue).


Relation of Ovulation and Menstruation. - Since human ovulation and menstruation both begin with puberty, recur at about twenty-eight day intervals, and discontinue during pregnancy and at the menopause, a close relation has long been inferred. The cessation of the menses after ovarian removal further indicates dependence. For many years the two processes were supposed to be synehronous. This belief was based upon clinical oliservations by Leopold, Ravano and others who tried to correlate the ages of corpora lutea with known menstrual histories. Since then, Meyer, Ruge, Schroder, Fraenkel, and Halban, utilizing better standardized corpora lutea, have presented convincing evidence that ovulation occurs most often between the fourth and fourteenth day after the menstrual onset. While correct as a generalization, this correlation is not rigid and often ova are liberated at other times. Moreover, in young girls ovulation may precede the inception of menstruation and it may occur in women during pregnancy and lactation or after the menopause.


Coitus and Insemination. - In most aquatic animals the eggs and sperm are discharged externally at about the same time and place. Their meeting depends largely upon chance, enhanced by the production of immense numbers of spermatozoa. Some animals increase the certainty of such cell union by a pscudocopulation ; thus, the male frog clasps the female and jiours his milt over the eggs as they are extruded. Many invertebrates and all amniote vertebrates have their sex cells unite inside the female - s body. This is effected by the sexual embrace termed copulation, or coitus. In general, those animals whose offspring reach maturity with reasonable surety (as the result of internal fertilization and postnatal care) produce fewer germ cells, especially ova, than those that leave fertilization to chance and development to hazard. The codfish produces 10,000,000 eggs in a breeding period, a sea urchin 20,000,000; in certain birds and mammals only a single egg is matured, yet the stock of each remains constant.


The purpose of coitus is to introduce spermatozoa into the vagina. The completed human sperm detach from the Sertoli cells, and clusters are moved along the efferent ductules into the epididymis. Here they become separate and motile, due to a secretion of the duct epithelium. The seminal fluid accumulates about the ampulla of the ductus deferens; its storage in the seminal vesicles is much questioned. At the climax of coitus ejaculation occurs and the spermatozoa, suspended in seminal fluid, are forcibly ejected. The seminal fluid, or semen, is a mixture chiefly of the secretions of the seminal vesicles, prostate, and bulbourethal glands, in which occur the spermatozoa. The volume of the ejaculate is about 3 c.c. and in it swim over 200,000,000 spermatozoa.


The outstanding functional feature of spermatozoa is their flagellate swimming. Because of this they were once regarded as parasites living in the seminal fluid. Forward progress is at the rate of about 2.5 mm. a minute, which, length for length, compares with the ordinary gait of man. An acid environment, such as the vagina, is deleterious or fatal; an alkaline medium, as furnished by the uterus, is favorable. Spermatozoa tend always to swim against feeble currents. This is important, as the outwardl^^ stroking cilia of the uterine tubes and uterus direct the spermatozoa by the shortest route to the ovum. They probably reach the ampulla of the uterine tube two hours or more after coitus.


Spermatozoa have been found motile in the uterine tube nine days after the admission of a patient to the clinic, and, according to her statement, three and one-half w^eeks after coitus. They have been kept alive eight days outside the body. It is not known for how long spermatozoa are capable of fertilizing ova. Keibel holds that this would certainly be more than a week. However, Lillie (1915) has shown with sea urchins that the ability to fertilize is lost long before vitality or motility is impaired, and Mall (1918) concludes that the duration of the fertilizing power of human spermatozoa is safely less than the corresponding period in the ovum, which is probably for fully 24 hours after ovulation. In the hen, spermatozoa remain functional three weeks; in bats six months; in bees five years.


FERTILIZATION

The formation, maturation, and meeting of the male and female germ cells are all preliminary to their actual union which definitely marks the beginning of a new individual. This penetration of ovum by spermatozoon and the fusion of their - pronuclei - constitute the process oi jertilization. In practically all animals, fertilization also starts the ovum dividing and thus initiates development in the ordinary sense. A few invertebrates, however, can develop without the aid of fertilization; this method is styled parthenogenesis, and in such eggs there is usually but one polar cell and hence no chromosome reduction.

Random movements of the sperm bring them in contact with ova. It is very doubtful whether there is any chemical attraction. In some forms, as for example fishes, tactile response keeps -the spermatozoa in contact with anything touched. In mammals, amphibia, and many invertebrates, the ovum is either naked or surrounded by a delicate vitelline membrane. Spermatozoa can enter such eggs at any point. Ova that are invested with heavy membranes usually have a definite funnel-shaped aperture, the micro pyle, through which the male cell must enter. Only motile spermatozoa are able to attach to the surface of an egg; it is probable that forces allied to phagocytosis, rather than vibrational energy, accomplish the actual - penetration. - In general, only one spermatozoon normally enters an egg; how others, endeavoring to penetrate, are thereafter excluded is not entirely clear. If accident or im]iaired vitality admits more than one sperm, development is abnormal and soon ends. On the contrary, some sharks, amphibia, reptiles, and birds normally exhibit such polyspermy. In all these cases, however, only one spermatozoon unites with the female pronucleus.


The fertilized ovum derives its nuclear substance equally from both parents, the cytoplasm (and yolk) almost entirely from the mother, the centrosome probably from the father.


The fundamental results of fertilization are: (i) the union of male and female pronuclei to form the cleavage nucleus (thus restoring the original number of chromosome pairs); (2) the initiation of cell division, â– or cleavage, in which all male and female chromosomes take part.


These two factors are separate and independent phenomena. It has been shown by Boveri and others that fragments of sea urchin - s ova containing no part of the nucleus may be fertilized by spermatozoa, segment, and develop into larvae. The female chromosomes are thus not essential to the process of cleavage. Loeb, on the other hand, proved that the ova of invertebrates may be made to develop by chemical and mechanical means without the cooperation of the spermatozoon {artificial parthenogenesis). Even adult frogs have been reared from mechanically stimulated eggs. These facts show that the actual union of the male and female pronuclei is not the means of initiating the development of the ova. In all vertebrates it is, nevertheless, the end and aim of fertilization.


Lillie maintains that the cortex of a sea urchin - s ovum produces a substance, fertilizin. This he regards as an amboceptor essential to fertilization, with one side chain which agglutinates and attracts the spermatozoa, and another side chain which activates the cytoplasm and initiates the cleavage of the ovum. According to Loeb, agglutination is proved in but few forms and Lillie - s interpretation fails to meet all the facts. Loeb holds that the spermatozoon actually activates the ovum to develop by increasing its oxidations and by rendering it immune to the toxic effects of oxidation.


Fertilization in the Mouse. - Normally, a single spermatozoon enters the ovum six to ten hours after coitus. While the second polar cell is forming, the spermatozoon penetrates the ovum and loses its tail (Fig. 17 A-C). Its head enlarges and is converted into the male projiuclcits (D). The pronuclei, male and female, approach (E) and resolve first into a spireme stage (F), then into two groups of 20 chromosomes (G). A centrosome, possibly that of the male cell (cf. Fig. 15 B), appears between them, divides into two, and soon the first cleavage spindle is formed (F-H). The 20 male and 20 female chromosomes arrange themselves in the equatorial plane of the spindle, thus making the original number of 40 (H). Fertilization is now complete and the ovum divides in the ordinay way ( 7 , /), the daughter cells each receiving equal numbers of maternal and paternal chromosomes.


Fertilization in Man. - The union of the human germ cells is believed usually to take place in the ampulla of the uterine tube, although it never has been observed in any primate except Tarsius. This conclusion is supported by direct observations on other mammals and by the frequency of tubal pregnancies at this site. Rarely ova become fertilized before entering the tube, but the possibility of fertilization after they have reached the uterus is usually denied.


Fig. 17. - Fertilization of the ovum of the mouse (Sobotta). X 500. A-D, Entrance of the spermatozoon and formation of the polar cells; D-E, development of the pronuclei ; F - J, union of chromosomes and the first cleavage spindle.


To be fruitful, the time of coitus and ovulation must roughly agree (p. 22), and, on the average, about one day is supposed to elapse between insemination and fertilization. Most conceptions occur during the week or ten days following menstruation; this is in harmony with the known data on ovulation time (p. 24).


While there are no direct observations on fertilization in man, the ]irocess has been studied throughly in several mammals. In all essentials it undoubtedly follows the common course as described for the mouse.


Superfetation.- If an ovum is liberated by a pregnant woman and fertilized at a later coitus, it may develop into a second, younger fetus. This rare condition, called sit perjctation, is often denied, yet in the early weeks of ])regnancy it is theoretically possible. Superfetation should not be confused with strikingly unequal twin development, due to nutritional or other inequalities.


HEREDITY AND SEX


The Significance of Mitosis and Maturation. - The complicated processes of mitosis serve the purpose of dividing accurately the chromatic substance of the nucleus in such a way that the self-pcrjietuating chromosomes of each daughter cell may be the same, both quantitatively and ciualitatively. This is important since it is believed by most students of heredity that chromatin particles, or genes, in the chromosomes bear the hereditary characters, and that these are arranged in definite linear order in particular chromosomes. At maturation there is a side by side union of like chromosomes, one member of each pair having come from the father, the other from the mother of the preceding generation; each member, however, carries the same general set of hereditary charaeters as its mate. At this stage of chromosomal conjugation there may be an interchange, or - crossing over, - of corresponding genes, resulting in new hereditary combinations. The reducing division of maturation separates whole chromosomes of each pair, but chance alone governs the actual assortment of paternal and maternal members to the daughter cells; this mitosis obviously halves the chromosome number characteristic for the species. The significance of the ecjuational maturation mitosis, beyond accomplishing mere cellular multiplication, is obscure.


Mendel’s Law of Heredity. - Experiments show that hereditary characters fall into two opposing groups, the contrasted pairs of which are termed allelomorphs. As an example, we may take the hereditary tendencies for dark and blue eyes. It is believed that there are paired chromatic particles, or genes, which are responsible for these hereditary tendencies, and that paired spermatogonial chromosomes bear one each of these genes. Each chromosome pair in separate germ cells may possess similar genes, both bearing dark-eyed tendencies or both blue-eyed tendencies, or opposing genes, bearing the one dark-, the other blue-eyed tendencies. It is assumed that at maturation these paired genes are separated along with the chromosomes, and that one only of each pair is retained in each germ cell.


In our example, either a blue-eyed or a dark-eyed tendency-bearing particle would be retained. At fertilization, the segregated genes of one sex may enter into new combinations with those from the other sex. Three combinations are possible. If the color of the eyes be taken as the hereditary character: (i) two - dark - germ cells may unite; (2) two - blue - germ cells may unite; (3) a - dark - germ cell may unite with a - blue - germ cell. The offspring in (i) will all have dark eyes, and, if interbred, their progeny will likewise inherit dark eyes exclusively. Similarly, the offspring in (2), and if these are interbred their progeny as well, will include nothing but blue-eyed individuals. The first generation from the cross in (3) will have dark eyes solely, for black in the present example is dominant, as it is termed. Such dark-eyed individuals, nevertheless, possess both dark- and blueeyed bearing genes in their germ cells; in the progeny resulting from the interbreeding of this class, the original condition is repeated - pure darks, impure darks which hold blue recessive, and pure blues will be formed in the ratio of 1:2:1 respectively. It is thus seen that blue-eyed children may be born of dark-eyed parents, whereas blue-eyed parents can never have dark-eyed offspring. Many such allelomorphic pairs of hereditary characters are known.


Cytoplasmic Inheritance. - Certain eggs show distinct cytoplasmic zones which cleavage later segregates into groups of cells destined to form definite organs or parts. In a sense this represents a refined sort of preformation, but prelocalization is a more exact term. From these facts Conklin and Loeb argue that the cytoplasm is really the embryo in the rough, the nucleus, through Mendelian heredity, adding only the finer details. Morgan, among others, refuses to admit the validity of this interpretation.


The Determination of Sex. - The sex-determining power lies in a chromosome that can be identified in many animals. This chromosome is termed the accessory, X, or sex chromosome. According to Painter (1923), humair obgonia contain 46 ordinary chromosomes and two X -chromosomes. At maturation the number is halved, and all oocytes and polocytes contain 23 -f X. The spermatogonia, on the contrary, contain 46 ordinary chromosomes, one X-chromosome and its diminutive mate, called the Y-chromosome. After maturation, therefore, half the spermatids have 23 -j- X, the remaining half have 23 -p y. When a spermatozoon with 23 + X fertilizes an ovum, the number is restored to 46 -p 2X and a female results. When a spermatozoon with 23 -p Y fertilizes, the outcome is 46 -p X -p Y and a male results.


Many animals lack the Y, and the male cells contain an odd number of chromosomes. Reduction then forms two classes of spermatozoa, those with the extra chromosome being female producing. In certain birds and moths the system is the exact reverse, inasmuch as the spermatozoa are all alike in chromosomal constitution while the eggs are of two sorts.




++++++++++++++++++++++++++++++++.

Chapter II Cleavage And The Origin Of The Germ Layers


Cleavage

The fertilized ovum promptly begins to form the new, multicellular individual by a process termed cleavage, or segmentation . This comprises orderly and rapid successions of mitoses which result in an aggregate of smaller cells, called blastomercs. Every blastomere receives the full assortment of chromosomes, half from each parent (Fig. 17 F-J).

The abundance and distribution of yolk in the egg so influences mitosis as to allow the following classification of cleavage: (A) Total. Entire ovum divides; holoblastic ova.

1. Equal. In isolecithal ova; blastomeres are of equal size; e.g., amphioxus and mammals.


2. Unequal. In moderately telolecithal ova; yolk accumulated at vegetal pole retards mitosis, and fewer but larger blastomeres form there; e.g., lower fishes and amphibia.


{B) Partial. Protoplasmic regions alone cleave; meroblastic ova.

1. Discoidal. In highly telolecithal ova; mitosis restricted to anim^d ]Jole; e.g., higher fishes, reptiles, and birds.

2. Superficial. In centrolecithal ova; mitosis restricted to the peri])heral cytoplasmic investment ; arthropods.



Cleavage in Amphioxus. - The early processes of development are easily understood in a primitive, fish-like form, Amphioxus. About one hour after fertilization, its essentially isolecithal ovum divides vertically into two nearly equal blastomeres (Fig. 18, 2). Within the next hour the daughter cells again cleave in the vertical plane, at right angles to the first division, thus forming four cells (3). Fifteen minutes later a third division takes place in a horizontal plane (4). As the yolk is somewhat more abundant at the vegetal poles of the four cells, the mitotic spindles lie nearer the animal pole. Consequently, in the eight-celled stage the upper tier of four cells is slightly smaller than the lower four. By successive cleavages, first in the vertical, then in the horizontal ]3lane, a 16- and 3 2 -celled embryo is formed (5, 6). The upper two tiers are now smaller, and a cavity, the blastocode, is enclosed by the cells. The embryo at this stage is sometimes called a morula because of its resemblance to a mulberry. In subsequent cleavages, as development proceeds, the size of the cells is diminished, while the cavity enlarges (7, 8). The embryo is now a blastnla, nearly spherical in form and about four hours old. The cleavage of the holoblastic Amphioxus ovum is thus total and nearly equal.


Fig. 18. - Cleavage in Amphioxus, viewed laterally (Hatschek). X 200. i. Mature egg, with one polar body (P. 5 .) ; the other missing. 2. Ovum partly divided into two blastomeres. 3. Four blastomeres. 4. Eight blastomeres. 5. Sixteen blastomeres. 6. Thirty-two blastomeres, hemisected to show the blastocoele, B. 7, 8. Total and hemisected blastul®.



Cleavage in Lower Fishes and Amphibia. - These ova contain enough yolk so that the nucleus and most of the cytoplasm lie nearer the upper, or animal pole. The first cleavage spindle appears eccentrically in this cytoplasm. The first two cleavage planes are vertical and at right angles, and the four resulting cells are equal. The spindles for the third cleavage are located near the animal pole, and the division takes place in a horizontal plane. As a result, the upper four cells are much smaller than the lower four (Fig. ig A). The large, yolk-laden cells divide more slowly than the upper, small cells (B-D). At the blastula stage, the cavity is small, and the cells of the vegetal pole are many times larger than those of the animal pole {E, F). The cleavage is thus total but unequal vertical but the inert yolk does not cleave. The segmentation is thus partial and discoidal. In the bird - s ovum, the cytoplasm is divided by successive vertical furrows into a mosaic of cells, which, as it increases in size, forms a cap-like structure upon the surface of the yolk (Fig. 20 A). These cells are separated from the yolk beneath by horizontal cleavage.


Fig. 20. - Cleavage of the pigeon - s ovum (redrawn from Blount). A, Blastoderm in surface view; B, in vertical section.


Fig. 19. - Cleavage and gastrulation in the frog. X 12. A-D, Cleavage stages; E, blastula; F, hemisection of E; G, early gastrula; u, hemisection of G. an., Animal cells; arch., archenteron; b'c., blastocoele; b - p., blastopore; ect., ectoderm; ent., entoderm; v - g., vegetal cells.


Cleavage in Higher Fishes, Reptiles and Birds. - The ova of these vertebrates contain a large amount of yolk. There is very little pure cytoplasm except at the animal pole, and here the nucleus is located (Fig. 6). When segmentation begins, the first plane of separation is furrows, and successive horizontal cleavages give rise to several layers of cells (Fig. 20 B). The space between cells and yolk mass may be compared to the blastula cavity of Amphioxus and the frog (Fig. 22). The cellular cap is termed the germinal disc, or blastoderm. The yolk mass, which forms the floor of the blastula cavity and the greater part of the ovum, may be compared to the large, yolk-laden cells at the vegetal pole of the frog - s blastula. The main yolk mass never divides but is gradually used up in supplying nutriment to the embryo which is developed from the cells of the germinal disc. At the periphery of the blastoderm, new cells form progressively until they enclose the yolk (Fig. 22 C).


Fig. 21. - Diagrams of cleavage ami the blastodermic vesicle in the raut^it (Thomson, after van Beneden). X 200.


Cleavage in Mammals. - The ovum of all the higher mammals, including man, is isolecithal and nearly microscopic in size. Its cleavage has been studied in several forms, but the rabbit - s ovum will serve as an example. The cleavage is complete and nearly equal (Fig. 21), a cluster of approximately uniform cells being formed within the zona pellucida. This corresponds to the morula stage of Amphioxus. Next, an inner mass of cells is formed that is equivalent to the germinal disc, or blastoderm of the chick embryo. The inner cell mass is overgrown by an outer layer which is termed the trophectoderm, because it later supplies nutriment to the embryo from the uterine wall. Fluid then appears between the outer layer and the inner cell mass, thereby separating the two except at the animal pole. As the fluid increases in amount, a hollow blastodermic vesicle results, its walls composed of the single-layered trophectoderm, except where this is in contact with the inner cell mass. It is usually spherical or ovoid in form, as in the rabbit, and probably such is the form of the human ovum at this stage. In the rabbit, the vesicle is 4.5 mm. long before it becomes embedded in the wall of the uterus; among ungulates, or hoofed animals, the vesicle is greatly elongated and attains a length of several centimeters, as in the pig.


Fig. 22 . - Diagrams of blastula homologies (Prentiss). . 4 , Amphioxus; B, frog; C, chick; D, mammal.



Comparing the mammalian blastodermic vesicle with the blastula stages of Amphioxus, the frog, and the bird, it will be seen that it is to be homologized with the bird - s blastula, not with that of Amphioxus (Fig. 22). In each case there is an inner cell mass of the germinal disc. The trophectoderm of the mammal represents a ])recocious development of cells, which, in the bird, later enveloji the yolk. The cavity of the vesicle is to be compared, not with the blastula cavity of Amphioxus and the frog, but with the yolk mass pins the cleft-like blastocoele of the bird's ovum. The higher mammalian ovum, although almost devoid of yolk, thus develops a - blastula - resembling that attained by the yolk-laden ova of reptiles and birds. That this similarity has an evolutionary significance is attested by discoidal cleavage in the highly telolecithal eggs of present-day monotreme mammals.


In the low primate Tarsius, cleavage and the blastodermic vesicle are well known. A four-celled Macacus ovum, with blastomeres nearly equal and oval in form, is the only cleavage stage yet observed among higher jirimates. In all placental mammals, segmentation of the ovum occurs during its passage down the uterine tube.




THE FORMATION OF ECTODERM AND ENTODERM (GASTRULATION)


The blastula and early blastodermic vesicle show no differentiation into layers. Such differentiation next takes place, giving rise first to the ectoderm and entoderm, and finally to the mesoderm. From these three primary germ layers all tissues and organs of the body are derived.

The processes of gastridation, by which ectoderm and entoderm arise, and of mesoderm formation will be treated separately.

Amphioxus and Amphibia. - The larger cells at the vegetal pole of the Amphioxus blastula fold inward (Fig. 23 A, B). Eventually, these invaginating cells obliterate the blastula cavity and come in contact with the outer layer (Fig. 23 C). The new cavity, thus formed, is the primitive gut, or archenteron, and its narrowed mouth is the blastopore. The outer layer of cells is the ectoderm, the inner, newly formed layer is the entoderm. The entodermal cells are henceforth concerned in the nutrition of the body. The embryo is now termed a gastrula (little stomach).


In amphibia, invagination begins at the junction of animal and vegetal cells (Fig. ig G). Externally, the blastopore appears as a crescentic groove. Since the vegetal cells are large and the blastocoele is relatively small, simple invagination fails. Hence, archenteron formation is aided by a lip-like overgrowth of rapidly dividing cells from the animal pole (Fig. ig H).


Fig. 23. - Gastrulation in Amphioxus. X 200.


Reptiles and Birds. - ^The germinal disc, or blastoderm, in these animals lies like a cap on the surface of inert yolk (Fig. 6). Since the enormous amount of yolk makes gastrulation as in Amphioxus and amphibians impossible, the process exhibits marked modifications.


There appears caudally on the blastoderm of reptiles a pit-like depression. From this invagination, a proliferation of cells forms a layer which spreads beneath the ectoderm. The inner layer, originating in this manner, is the entoderm, and the region of the pit, where ectoderm and entoderm are continuous, is the blastopore. In Fig. 27 A these changes are complete.


Fig. 24. - Gastrulation in the pigeon, as shown by a longitudinal section of the blastoderm (redrawn after Patterson). X 50.


In birds, the caudal portion of the blastoderm is rolled or tucked under, the inner layer formed in this way constituting the entoderm (Fig. 24). The marginal region, where ectoderm and entoderm meet, bounds the blastopore, while the space between entoderm and yolk is the archenteron.


Mammals. - Cells on the under surface of the inner cell mass become arranged in a definite sheet, the entoderm (Fig. 2^ A). It is usually said to arise by s])litting, or delamination, although there are attempts to prove ingrowth from a - blastopore. - In most mammals, the entoderm spreads rapidly and lines the blastodermic vesicle (Fig. 38) but in Tarsius, the entoderm forms a much smaller sac (Fig. 25 B, C). The youngest human embryos known (Fig. 40) indicate a previous origin of entoderm much as in Tarsius.



Fig 23. - Gastrulation in the low primate, Tarsius, as demonstrated by sections of the blastodermic vesicle (redrawn after Hubrecht). X 260.


ORIGIN OF THE MESODERM, NOTOCHORD AND NEURAL TUBE .


Amphioxus and Amphibia. - The dorsal portion of the inner sheet, which forms the roof of the archenteron in Amphioxus, gives rise to paired, lateral diverticula, the ccdonuc pouches (Fig. 26). These separate both from a mid-dorsal plate of cells (the future notochord), and from the entoderm of the gut, and become the primary mesoderm. The mesodermal pouches grow ventrad and their cavities form the coelom, or body cavity. Their outer layers, with the ectoderm, constitute the body wall, or somatopleure; their inner layers, with the gut entoderm, form the intestinal wall, or splanchnopleure. In the meantime, a dorsal plate, cut off from the ectoderm, folds into the neural tube (anlage of the nervous system), and the notochordal plate becomes a cord, or cylinder, of cells (axial skeleton) extending the length of the embryo. In this simple fashion the ground plan of the chordate body is attained.


Fig. 26. - Origin of the mesoderm in Amphioxus (Hatschek). X 425. a/, Lumen of gut; r//., notochord : ai\, ccelom; crrl.p., coelomic pouch; ect., ectoderm; ent., entoderm; n.c., neural canal; n.g., neural groove.


Fig. 27. - Longitudinal sections of the snake - s blastoderm, at various stages, to show the origin of the notochordal plate (adapted after Hertwig).


In amphibia, solid mesodermal plates arise in a similar location and extend laterally between the ectoderm and entoderm. Later, these plates split into two layers and the cavity so formed is the coelom (cf .3S)' The notochord also originates as in Amphioxus.


Reptiles, - The same pocket-like depression in the caudal portion of the blastoderm, that gave rise to the cells of the entodermal layer, now invaginates more extensively and forms a pouch which pushes forward between ectoderm and entoderm (Fig. 27 A and B). The size of the invagination cavity varies in different species; in some it is elongate and narrow, lieing confined to the middle line of the blastoderm. The floor of this pouch soon fuses with the underlying entoderm, and the two thin, rupture, and disappear, thus putting the cavity of the pouch temporarily in communication with the space (archenteron) beneath the entoderm (Fig. 27 C). The cells of the roof persist as the notochordal plate, which later liccomes the notochord. The neural folds arise before the mouth of the pouch (blastopore) closes, and, fusing to form the neural tube, incorporate the blastopore into its floor. This temporary communication between the neural tube and the primitive enteric cavity is the neurenteric canal (cf. Fig. 27 C) \ it is found in all the vertebrate groups (cf. Fig. 58). A transverse section through the invaginated pouch, at the time of rupture of its floor, and through the underlying entoderm will make clear the lateral extent of these changes (Fig. 28).



Fig. 28. - Transverse section of a snake - s blastoderm, at a level corresponding to the middle of


Fig. 27 C (adapted after Hertwig).



From about the blastopore, and from the walls of the pouch, mesodermal plates arise and extend like wings between the ectoderm and entoderm (Fig. 28). As in amphibia, they later separate into outer (somatic) and inner (splanchnic) layers enclosing the Primitive groove coelom. The relation between notochordal plate, mesoderm, and entoderm, shown in Fig. 28, resembles strikingly the conditions in Amphioxus (Fig. 26 A).


Birds - Due to the modified gastrulation in reptiles, birds, and mammals through the influence of yolk, a structure known as the primitive streak becomes important. An account of its formation and significance, based on conditions found in the bird, may be introduced conveniently at this place.


Shortly after the formation of entoderm, an opaque band appears in the median line at the more caudal portion of the blastoderm (Fig. 29).


Fig. 29. - BlaStoderm of a chick cmliryo at the stage of the primitive streak. X 20.


Along this primitive streak, which is at first merely a linear ectodermal thickening, there forms a shallow primitive groove, and at its forward end the streak ends in a knob, the primitive knot, or node (of Hensen). The primitive streak becomes highly significant when interpreted in the light of the theory of concrescence, a theory of general application in vertebrate development. It will be remembered that the entoderm of birds arises by a rolling under of the outer layer along the caudal margin of the blastoderm. As the blastoderm expands, it is believed that a middle point on this margin remains fixed (Fig. 30 A) while the edges of the margin on eaeh side are carried caudad and brought together (B, C). Thus, a crescentic margin is transformed into a longitudinal slit. Since this marginal lip originally bounded the blastopore (p. 35), the longitudinal slit must also be an elongated blastopore whose direction has merely been changed. The lips of the slit fuse, forming the primitive streak (D). The teachings of comparative embryology support these conclusions, for the neurenteric canal arises at the cranial end of the primitive streak, the anus at its caudal end, while the primary germ layers fuse in its substance. All these relations exist at the blastopore of the lower animals.



Fig. 30. - Diagrams to illustrate the formation of the primitive streak according to the theorjof concrescence. The expanding blastoderm is indicated by dotted circles.



Fig. 31. - Median longitudinal section of a chick embryo at the stage of the primitive streak and head process. X 100.


From the thickened ectoderm of the primitive streak a proliferation of cells takes place, and there grows out laterally and caudally between the ectoderm and entoderm a solid plate of mesoderm which soon splits into somatic and splanchnic layers (Fig. 316). An axial growth, the head process, or notochordal plate, likewise extends forward from the primitive knot and fuses at once with the entoderm (Figs. 31 and 317). Since the primitive streak represents a modified blastopore, it is evident that this cranial extension, the head process, corresponds to the pouch-like invagination concerned in the formation of notochord and mesoderm in reptiles. In birds, the fusion of the head process with the entoderm, the relation of mesodermal sheets to it laterally, the formation of the notochord from its tissue and the occasional traces in it of a cavity continuous with the primitive pit (that is, a notochordal canal), all recall the conditions described for the less modified invagination in reptiles. The primitive groove is the visible result of mesoderm proliferation from the tissue of the streak.


Fig. 32. - . 1 , Embryonic disc of the Mateer human embryo, at the stage of the primitive streak (after Streeter). X 50. B, Embryonic disc of the Ingalls human embryo, with primitive streak and head process. X 26.


Mammals - A typical primitive streak appears on the blastoderm of mammals (Fig. 32 A). The under side of its ectodermal thickening proliferates mesodermal cells which grow laterally and caudally (Fig. 33). All three germ layers fuse in the primitive knot and from it a head process soon extends forward (Fig. 32 B).


Fig. 33. - Transverse section through the primitive streak of the Mateer human embryo (Fig. 32 ,1 ) to show the origin of mesoderm (redrawn after Streeter). X 185.


The head process of many mammalian embryos contains a cavity {notochordal canal), which in some cases is of considerable size, opening at the primitive pit (Fig. 34). As in reptiles, the floor of this cavity fuses with the entoderm, and the two rupture and disappear. Portions of the floor, still persistent, are shown in Fig. 34. Thus a canal, later enclosed by the neural folds, and then known as the neurenteric canal, puts the dorsal surface of the blastoderm in communication with the enteric cavity beneath the entoderm (Figs. 57 and 58). The roof of the head process, or notochordal plate, is for a time associated closely with the lateral mesoderm (compare these relations in reptiles. Fig. 28), but eventually it becomes the notochord.



Fig. 34. - Median sagittal section through the primitive knot and head process of the Ingalls human embryo (Fig. 32 5 ). X 200.


The mesoderm grows rapidly around the wall of the blastodermic vesicle, until Anally the two wings fuse ventrally. The single sheet then splits into two layers, the cavity between being the coelom, or body cavity (Fig. 35). The outer mesodermal layer (somatic), with the ectoderm, forms the somatopleure, or body wall; the inner splanchnic layer, with the entoderm, forms the intestinal wall, or splanchnoplcure. The neural tube having in the meantime arisen from the neural folds of the ectoderm, there is present the ground plan of the vertebrate body, the same in man as in Amphioxus (Fig. 35 A).



Fig. 35. - Diagrammatic transverse sections of mammalian embryos. . A , The origin and spread of mesoderm (Brjme); B, the further differentiation of mesoderm, and the body plan (Prentiss).



Mesoderm, but not a coelom, is already present in the youngest human embryo yet examined (Fig. 40 A). In Tarsius, a low primate, the mesoderm has two sources: (i) From the splitting of ectoderm at the caudal edge of the blastoderm; this constitutes the extra-embryonic mesoderm and takes no part in forming the body of the embryo. (2) The intra-embryonic mesodertu, which gives rise to body tissues, takes its origin from the primitive streak as in the chick and lower mammals. The origin in the human embryo is probably much the same as in Tarsius.


Homologies of Mesoderm and Notochord. - In Amphioxus and amphibia, transverse sections (Fig. 26) apparently show that the mesoderm and notochord are folded directly from dorsal gut-entoderm. Yet such is illusory, for the roof of the archenteron grows from the dorsal lip of the blastopore. Longitudinal sections prove that as the embryo elongates, this caudal, formative region progressively adds to the roof of the primitive gut. Hence, both notochord and mesoderm originate from the indifferent tissue at the blastopore where ectoderm and entoderm meet. In reptiles, birds, and mammals the mesoderm arises as lateral proliferations from the primitive streak, whereas the notochordal plate (head process) is a - growth - from its anterior end (cf. p. 40). But, as the primitive streak is a modified, fused blastopore (p. 39), their origin is fundamentally like that in Amphioxus and amphibia. From its external position and developmental relations the parent blastoporic tissue is often styled ectoderm; especially in embryos with a primitive streak this is convenient and unobjectionable. It will be evident, therefore, that although the ultimate source of both mesoderm and notochord is from an indifferent - ectoderm, - the notochord, once formed, is true mesoderm.


The Notochord or Chorda Dorsalis. - As the primitive streak recedes caudad during development, the head process is progressively lengthened at its expense. Ultimately, the primitive streak becomes restricted to the tail region and serves as a growth zone there, whereas the entire remainder of the body is built around the head process as an axis. The original position of the primitive knot corresponds to the junction of head and neck in the future body. In later stages, the rod-like notochord extends from head to tail in the midplane (Fig. 91). It becomes enclosed in the centra of the vertebrae and in the base of the cranium, and eventually degenerates. In Amphioxus, the notochord forms the only axial skeleton, and it is persistent in the vertebrae of fishes and amphibians. In adult man, traces are found as - pulpy nuclei - in the intervertebral discs.


Twinning. - LTsually but one human ovum is produced and fertilized at coitus. The simultaneous development of two or more embryos is due commonly to the ripening, expulsion, and subsequent fertilization of an equal number of ova. In such cases ordinary, or fraternal livins, triplets, and so on, of the same or opposite sex result; properly speaking, they are not twins at all. Identical, or duplicate twins, that is, those true twins always of the same sex and strikingly similar in form and feature, arise from two growing points on the embryonic cell mass, each of which develops as a separate embryo within the common chorion. The identical quadruplets of certain armadillos are known to result from the division of a single blastoderm into four parts. Separate development of the cleavage cells can also be produced experimentally in many of the lower animals.

Occasionally twins are conjoined. All degrees of union, from almost complete separation to fusion throughout the entire body-length, are known. If there is considerable disparity in size, the smaller is termed the parasite; in such cases the extent of attachment and dependency grades down to included twin (fetus in fetu) and tumor-like fetal inclusions. In some - monsters - the duplication is partial, as doubling of the head or legs. All of these terata, like identical twins, are the products of a single ovum, but variably fused in accordance with their original degree of separation on the blastodermic mass.

Stockard reduces the primary cause of all non-hereditary abnormal developments, including twins, to a single factor - developmental inhibition or arrest; the exact type of deformity that results depends solely on the precise moment when the interruption occurs. A slowing of the developmental rate at the critical moment (gastrulation) when one of several potential embryonic axes is about to assert its dominance, causes it to lose its original advantage and one or more neighboring points may then appear as additional axes. The direct cause of the arrest is referred to retarded oxidations.




CHAPTER III. IMPLANTATION AND FETAL MEMBRANES


The conditions under which vertebrate eggs develop vary markedly. In all vcrtel)rates below mammals the eggs are laid and develop in the surrounding medium, aided sometimes (especially in reptiles and birds) by parental protection and incubation. As a group, the mammals alone develop their young within the genital tract of the mother.


The embryos of fishes and amphibia grow rapidly to immature forms capable of independent existence. All other vertebrates are much farther advanced at Ihrth and accordingly form various organs, of use during develoi)ment only. Especially in higher mammals has the absence of yolk, and the resulting physiological dependence upon the mother, led to the greatest elaboration of these ajopendages.


Such fetal organs include the yolk sac and stalk, the allantois, amnion, and chorion. They have to do with the nutrition and respiration of the embryo, and the elimination of katabolic wastes. In higher mammals, the chorion is associated intimately with the uterine mucosa and forms with it an important organ called the placenta.


THE FETAL MEMBRANES OF REPTILES AND BIRDS

Development is similar in both classes. The chick illustrates typically the manner of membrane formation.


Amnion and Chorion. - The embryo develops in the center of the blastoderm, which first lies like a disc upon the massive yolk (Fig. 6). Later, the periphery of the blastoderm, not concerned in embryo formation, expands and encloses the yolk mass. This envelope consists of somatopleure and splanchnopleure, separated by the coelom (Fig. 4). The amnion and chorion arise from the somatopleure. This double layer (ectoderm and somatic mesoderm) is thrown up into crescentic folds, just in front of and behind the embryo (Fig. 36 A). Gradually, the hood-like folds close in from all sides until they meet and fuse over the embryo ( Fig. 36 B-C ) . The inner somatopleuric layer, thus formed, is the amnion; it constitutes a protective sac, lined with ectoderm and soon filled with fluid, within which the embryo is suspended. The outer of the two somatopleuric sheets is the chorion. It lies next the shell and is separated by the extra-embryonic coelom from the enclosed embryo and its other membranes (Fig. 37).


Yolk Sac. - As the embryo enlarges, its original connection with the extra-embryonic blastoderm becomes a slender stalk, uniting embryo and yolk (Fig. 37). It is designated the yolk stalk, whereas the yolk, enveloped by extra-embryonic blastoderm, is the yolk sac. Vitelline blood vessels ramify on the surface of the yolk sac and through them all the food material of the liquefied yolk is conveyed to the chick during the incubation period.



Fig. 36. - Diagrams in a sagittal plane illustrating the development of the fetal membranes of most amniotes (after Gegenbaur in McMurrich). Ectoderm, mesoderm, and entoderm are represented by heavy, light, and dotted lines respectively. .1/., Allantois: Am., amniotic cavity; I 5 .yolk sac.


Fig. 37. - Diagram of a five-day chick embryo and its membranes (Marshall). X 1.5.


Allantois. - There is an early outpouching of the ventral floor of the gut, near its hind end. This entodermal diverticulum pushes outward into the extra-embryonic coelom, carrying before it an investment of splanchnic mesoderm (Fig. 36). It forms a vesicle, known as the allantois, which develops rapidly into a large sac, connected to the hind-gut by the narrower allantoic stalk (Fig. 37). Finally, the allantois flattens and fuses with the chorion, just underlying the porous shell (Fig. 36 D). The blood vessels that ramify in the combined mesodermal wall are situated favorably for gaseous interchange, and the allantois becomes the embryonic respiratory organ. The allantoic cavity also serves in its primitive capacity as a reservoir for the excreta of the embryonic kidneys, and the wall assists in the absorption_of albumen.


THE FETAL MEMBRANES OF MAMMALS

Amnion and Chorion. - In most mammals these membranes arise by folding, as in reptiles and birds. Some (guinea pig; hedgehog; bat; primates) form an amnion precociously in an entirely different manner. In the bat, fluid-filled clefts appear in the interior of the embryonic cell mass; these coalesce and constitute the amnion cavity (Fig. 38). Later, a layer of somatic mesoderm envelops its ectodermal roof and the structural outcome is identical with the type derived by folding. The deer and sheep show a method transitional between these extremes; the embryonic mass hollows and its roof ruptures; then the definitive amnion develops by folding. The same group that derives an amnion by dehiscence, forms a chorion from the outer trophectoderm layer of the blastodermic vesicle, to which somatic mesoderm is added (Fig. 40).


Yolk Sac. - The yolk sac of monotremes resembles that of birds, but in higher forms an actual yolk mass is lacking. There are numerous early developmental variations. In the majority, the yolk-sac entoderm spreads beneath the trophectoderm shell and for a time lines it (Fig. 38) ; when the extra-embryonic mesoderm and coelom appear, the entoderm becomes clothed with the splanchnic layer and the sac is reduced in relative size. On the contrary, the yolk sac of primates is small from the first and remains as a diminutive central vesicle (Figs. 25 and 40). In rodents, carnivores, and split-hoofed mammals it early attains a large size, but ceases growth as the allantois comes to prominence. The splanchnic mesoderm of all groups bears the vitelline blood vessels. Many animals with a highly developed yolk sac effect an intimate association (through union with the chorion) with the uterine mucosa. There is thus formed a transitory yolk-sac placenta. In some marsupials and insectivores this relation persists.


Allantois. - Alany mammals, like reptiles and birds, form an allantois by the sacculation of gut-splanchnopleure into the extra-embryonic coelom. In some it remains small, and, especially in certain marsupials, does not come in contact with the chorion. On the contrary, in carnivores and ungulates it becomes very large and lines the chorionic sac (Fig. 39). A goat embryo of two inches has an allantois two feet long.


Fig. 38. - Stages of amnion formation in the bat (Van Beneden). X about 160.


Primates have a tiny, tubular allantois; it grows into and lies within the body stalk, which is a bridge of mesoderm connecting the embryo to he chorion (Fig. 40 D). Allantoic, or umbilical blood vessels accompany he allantois.


The Placenta. - The egg-laying monotremes develop under the same nutritive and respiratory conditions as do reptiles and birds. The marsupials, after a brief gestation period, give birth to immature young; their chorion, therefore, remains as a smooth membrane but in close apposition with the vascular uterine mucosa. The yolk sac is large and in some forms it unites with the chorion, apparently to serve as a nutritive path from uterus to embryo.


In all higher mammals, the chorion is beset with vascular villi and there is a more or less intimate relation, which persists throughout gestation, between the uterine mucosa and the chorionic vesicle. This arrangement results in the formation of an organ, the placenta, specialized for the nutrition of the embryo and for its respiration and excretion.


Fig. 39. - Diagram of the fetal membranes and allantoic placenta of a pig embryo, in median sagittal section (adapted by Prentiss).


The form and extent of the placenta vary in accordance with the final distribution of the chorionic villi. The pig and horse have villi diffusely scattered over the entire chorion. In ruminants, they occur in broadly scattered tufts, interspaced with smooth stretches of chorion. The villi of carnivores constitute a girdle-like band about the chorionic sac. In rodents, insectivores, bats, and primates, the villi are limited to a patchlike disc (Fig. 48).


There is likewise a structural series, based on the degree of fetal maternal intimacy. At the bottom of the scale stands the mere apposition of the uterine mucosa and the avillous chorion of marsupials.


Simplest of the forms with chorionic villi is the condition illustrated by the pig or horse (Fig. 39). The allantois, developing as in the chick, comes in contact and fuses with the chorion. Allantoic vessels lie in the combined mesoderm. Meanwhile, the external ectoderm of the amnion has closely applied itself to the uterine epithelium, and, when the chorionic villi appear, they fit into corresponding pits in the mucosa. Nutritive substances and oxygen from the maternal blood must pass through both layers of epithelium before entering the allantoic vessels. In the same manner, waste products from the embryo pass in the reverse direction. The allantois has therefore become important, not only as an organ of respiration and excretion, as in reptiles and birds, but also as an organ of nutrition. Through its vessels it has taken on the function belonging to the yolk sac of lower vertebrates, and the rudimentary, yolkless sac of higher mammals is now explained.


This general scheme of the ungulates is modified by an advance among its ruminant subgroup. Here the villi penetrate deeper and come in closer relation with the connective tissue about the maternal vessels by a partial destruction of the uterine epithelium. At the end of gestation the chorionic villi of the pig, horse, and ruminant are merely withdrawn, and the maternal mucosa is not lost.


In carnivores there is marked destruction of the mucosa, so that the chorionic epithelium about the maternal vessels is separated from the circulating blood by endothelium alone.


The highest type, as in rodents and primates, is characterized by a superficial erosion and destruction of the uterine mucosa, so that the chorionic villi, dangling in cavernous spaces, are bathed by the maternal blood which issues from eroded vessels (Fig. 34). In this and the preceding type, the changes are so profound and the fusions so intimate that the mucosa is largely sloughed at birth as a decidua. The chorion was important in the ungulate chiefly as it brought the allantois into close relation with the uterine wall, but in man and most unguiculates it assumes the several placental functions, and the allantois, now superseded like the yolk sac, in turn becomes rudimentary.


THE FETAL MEMBRANES OF MAN


Amnion. - -In the youngest known human embryo (Miller) the embryonic mass is solid (Fig. 40 A), but its ectoderm indicates a stage preparatory to the formation of amnion clefts. As an amniotic cavity is present in the slightly older embryo described by Bryce-Teacher (Fig. 40 B), the method of origin must be by direct splitting as in the bat (p. 46). These specimens likewise lack a coelom in the precociously formed extra-embryonic mesoderm, whereas all older embryos possess somatic and splanchnic layers bounding a more or less extensive coelomic cleft (Fig. 40 C). Somatic mesoderm then covers the primitive ectodermal roof of the amniotic cavity (Fig. 40 D) ; this order of layering is identical in all amniotes.


At first there is a broad union between the amnion and the external shell of t rophectoderm (Fig. 40 C), but this becomes reduced by the continued extension of the coelomic cavity until presently it is limited to the caudal end of the embryo alone (Fig. 40 D). This narrow, mesodermal bridge, into which the allantois and its vessels grow, is the body stalk (Fig. 43).



Fig. 40. - Diagrams of early human embryos (adapted by Prentiss). A, Miller (modified); B, Bryce-Teacher (modified); C, Peters; D, Spee.


Hence, from the first, the human amniotic cavity is closed. The base of the amnion is attached to the periphery of the embryonic disc, which also constitutes the floor of the cavity (Fig. 32 A). The amnion becomes a thin, pellucid, non-vascular membrane, lined with a simple epithelium (Figs. 43, 61 and 65). The amniotic cavity enlarges rapidly at the expense of the extra-embryonic coelom, and, at the end of the second month, fills the chorionic sac (Fig. 51). It then attaches loosely to the chorionic wall, thereby obliterating the extra-embryonic body cavity (Fig. 50).


Amniotic fluid fills the sac. Its immediate origin (fetal or maternal) is disputed. During the early months of pregnancy the embryo is suspended by the umbilical cord in this fluid (Fig. 51). Throughout gestation the amniotic fluid serves as a protective water cushion, equalizing pressures and preventing adherence of the amnion. At parturition, it acts as a fluid wedge to dilate the uterine cervix. The embryo is protected from maceration by a fatty skin-secretion, the vernix caseosa.


During the early stages of childbirth the membranes usually rupture, and about a liter of amniotic fluid escapes as the - waters. - If the tough amnion fails to burst, the head is delivered enveloped in it, and it is then popularly known as the - caul. - Anomalies. - When the amniotic fluid is excessive in volume, the condition is designated ' hydramuios. - If less than the optimal amount is present, the amnion may adhere to the embryo and cause malformations. Fibrous bands sometimes extend across the amnion cavity. As pressure increases during growth, they may cause scars and the splitting or even amputation of parts.


Fig. 41. - Section of Peters - 0.19 mm. human embryo (about fifteen da}^s). The portion of extra-embryonic ccelom shown is limited below by a strand of the magma reticulare.


Yolk Sac. - The entodermal portion of the Miller embryo is solid (Fig. 40 A), but in all other early specimens it forms a small vesicle, lined with a single layer of entoderm and covered with splanchnic mesoderm (Figs. 40 B-D, 41 and 43). In embryos of 1.5 to 2.0 mm., the entodermal roof of this vesicle begins to form the fore- and hind-gut which are then connected by a slightly narrowed region to the yolk sac proper (Figs. 43 . and 44). With the growth of the head- and tail regions of the embryo there is an apparent progressive constriction of the yolk sac (Figs. 60, 61 and 64). This, however, is a deception. Both embryo and yolk sac enlarge, whereas the region of union lags in transverse development but elongates into the slender yolk stalk (Fig. 42).


The yolk stalk becomes incorporated in the umbilical cord (Figs. 45, 64 and 65). It loses its attachment with the gut in embryos of 7 mm. and soon degenerates. Even earlier, the yolk sac has attained its final diameter of about i cm. ; it persists and may be found at birth adherent to the amnion in the placental region (Fig. 55). The yolk sac of man is a vestige containing a coagulum but no yolk (Fig. 41). Blood vessels arise very early in its mesoderm (Figs. 43 and 44) and institute a vitelline circulation with the embryo.


Fig. 42. - Yolk sac and Stalk of a 20 mm. human embryo (Prentiss). X u.


Anomalies. If that portion of the yolk stalk between the intestine and umbilicus remains pervious it constitutes a fecal fistula through which intestinal contents may escape.

In 2 per cent of all adults there is a persistence of the proximal end of the yolk stalk, to form a pouch, Meckel - s diverticulum of the ileum. This varies between 3 and 9 or more cm. in length and lies about 80 cm. above the colic valve. The divei'ticulum is important surgically as it sometimes telescopes into the intestinal lumen and occludes it.


Allantois. - Although the allantois is absent in the youngest embryos known, it nevertheless appears very early - even before the gut. In the Spee specimen, the allantois is a slender tube extending into the mesoderm of the body stalk (Fig. 43). It never becomes saccular, as in most lower amniotes. Since the human allantois arises so precociously, it does not develop as an evagination of the hind-gut into the extra-embryonic coelom; yet the body stalk, which contains the allantois, represents mesoderm into which the coelom has failed to penetrate.


Elongation extends the allantoic tube as far as the chorion (Figs. 44, 71 and 184), and, when the developing umbilical cord includes the allantois as a component, it at first is as long as the cord (Figs. 45 and 51). Soon, however, growth ceases and at birth the only remnant is a tenuous, and generally discontinuous, solid strand.


Fig. 44. - Mali - s 2.0 mm. human embryo in median sagittal section (adapted by Prentiss).X 23.


Umbilical blood vessels accompany the allantois; these also reach the chorion and vascularize it (Figs. 51 and 184). When the chorion becomes a part of the placenta it performs all the functions of nutrition, respiration, and excretion. Like the yolk sac, the allantois is a superseded rudiment.


Chorion. - The human chorion is derived directly from the trophectoderm layer of the blastodermic vesicle to which is added extra-embryonic mesoderm (Fig. 40). The trophectoderm of the youngest known embryos has already given rise to an outer syncytial layer, the irophodcrm, but the mesoderm is solid. In slightly older specimens, the mesoderm is cleft by the extra-embryonic cmlom and its outer, or somatic, layer lines the chorion (Figs. 40 B-I) and 46). The chorion forms villous processess (Fig. 48). At first these are solid ectoderm, the primary villi (Fig. 40 C), but soon the chorionic mesoderm invades them as central cores (Fig. 43) and allantoic, or umbilical blood vessels ramify in their branches. Such villi are secondary, or true villi (Figs. 51 and 65). The further history of the chorion is inseparable from placental development (p. 62).


Umbilical Cord. - As the embryo enlarges, its ventral, unclosed area, bounded by the edge of the amnion, becomes relatively smaller (Fig. 45 A, 5 ). For a time the amnion attaches close to the embryo, but, during the sixth week, growth of the adjoining body wall, accompanied by an elongation of the body stalk, causes the amnion to recede from the umhilicus. The tubular structure thus formed is the itmhilical cord (Fig. 45 C). It encloses both yolk stalk and allantois, and includes a portion of the coelom. Henceforth, the umbilical cord connects the embryo to that part of the chorion which constitutes the fetal half of the placenta (Figs. 51 and 55). The umbilical cord is actually an embryonic growth, and the amnion merely attaches to its distal end ( Fig. 65).


The cord is covered with ectodermal epithelium and contains, embedded in mucous tissue (jelly of Wharton): (i) the yolk stalk (and in early stages its vitelline vessels); (2) the allantois; (3) the allantoic or umbilical vessels (two arteries and a single, large vein ) . The mucous tissue, peculiar to the umbilical cord, comes from mesenchyme; it bears neither capillaries nor nerves. Between the sixth and tenth weeks, the gut extends into the coelom of the cord and forms a temporary umbilical hernia there (Fig. 96). After it is withdrawn, the cavity of the cord disappears.


The mature cord is about 1 .5 cm. in diameter and attains an average length of 50 cm. Its insertion is usually near the center of the placenta (Fig. 56), but may be marginal or even on the adjoining membranes. A spiral twist appears (Fig. 53), just how is not known, and the blood vessels sometimes curl in masses which cause external bulgings, designated - false knots. - True knots are known also. The cord may wind about the neck or extremities of a fetus and induce atrophy or even amputation.


Fig. 45. - Diagrams of the development of the human umbilical cord (DeLee). a.c., Amniotic cavity; exc., extra-embryonic coelom.


Implantation and Early Mucosal Relations During the events of cleavage and the formation of a morula and blastodermic vesicle, the ciliated lining of the uterine tube steadily transports the ovum downward. Early in this period of migration and development, the ovum loses its corona radiata cells and pellucid membrane. In about eight days it probably reaches the uterus, having attained a stage something like Fig. 40 A, although the vesicle is only about 0.2 mm. in diameter. It is evident, therefore, that the foregoing sections of this chapter describe changes which occur largely after implantation, rather than before it.


Fig. 46. - Section through a human embryo of 0.19 mm., embedded in the uterine mucosa (semidiagrammatic after Peters), am., Amniotic cavity; hS., body stalk; eel., ectoderm of embryo; ent., entoderm; ?nes., mesoderm; yS., yolk sac.


Implantation comprises the process by which the embryonic vesicle becomes embedded in the uterine mucosa. Actual observations on the human ovum are lacking, but from careful studies on the earliest specimens, and from more complete observations on other mammals, the course of events is reasonably certain.


The ovum penetrates the mucosa as would a parasite, the trophoderm supposedly producing an enzyme which digests away the maternal tissues until the embryo is entirely embedded. The Peters specimen, shown in Fig. 46, is well established and the chorionic vesicle has an internal diameter of more than a millimeter. Its point of entrance is marked by the customary fibrin clot which soon disappears, and the defect is repaired.


Continued rapid growth of the embryo necessitates a correspondingly progressive erosion of the maternal tissues. This causes extravasations of blood which collect in large vacuoles in the invading trophoderm and form blood lacunae (Fig. 46). The lacunce break up the trophoderm into solid cords, composed of both the inner cellular and outer syncytial layers. These constitute the primary villi. It is the syncytial layer that is active in the destruction of the uterine tissues, and probably also in the absorption of blood and tissue products (emhryotroph) for the early nutrition of the embryo.


Next, there are changes leading to the definitive [hemotrophic) type of nutrition. Chorionic mesoderm extends into the primary villi, and branching secondary or true villi result (Figs. 43 and 47). During the development of villi the blood lacunas in the original trophoderm shell expand, run together, and produce intervillous spaces which surround the villi and bathe their epithelium (Fig. 47). The formerly Spongy trophoderm is now reduced to a continuous layer covering the outer surfaces of the villi and chorion. Branches of the umbilical vessels develop in the mesoderm of the chorion and villi (Fig. 51). The mesodermal core of each villus and its branches is then covered by a two-layered epithelium; an inner, ectodermal layer (of Langhans) with distinctly outlined cuboidal cells, and an outer, syncytial trophoderm layer (Figs. 47 and 53 A). The epithelium also forms solid columns of cells which anchor the ends of certain villi to the uterine wall (Fig. 47),


Fig. 47. - Diagram of the early development of chorionic villi and placenta (after Peters).


In the vessels of the chorionic villi, the chorionic circulation of the embryo is established. The blood vessels of the uterus open into the intervillous blood s]iaces, and here the maternal blood circulates and bathes the syncytial trophoderm of the villi (Figs. 47 and 54). The transfer of nutritive substances and oxygen to the fetal blood takes place through the walls of the chorionic villi, whereas fetal wastes pass in the reverse direction. The tro])hoderm, like endothelium, prevents the coagulation of maternal blood. According to Mall, it also forms a wall which dams or ulugs the maternal blood vessels as soon as eroded, and, with the decidua (p. 62), limits the flow of blood into the intervillous spaces.


Villi at first cover the entire surface of the chorion (Fig. 40 D). As the embryo enlarges, the villi next the uterine cavity become both compresSed and remote from the Idood supply (Fig. 51). During the fourth week these villi atrophy and disappear (Fig. 48). This leaves a smooth surface, called the chorion Laeve. The villi adjacent to the uterine wall persist as the chorion frondosum and become the fetal part of the placenta (Fig. 49),



Fig. 48. - Human chorionic vesicles of five and seven weeks (De Lee). The chorion laeve and chorion frondosum are apparent. Natural size.


The Decidual Membranes


Two sets of important changes take place normally in the uterine mucosa. One of these is periodic, between puberty and the menopause, and is the cause of menstruation. It is comparable to the oestrus cycle in lower animals, and may also be regarded as preparatory to the second set of changes which appear only in pregnancy and give rise to the decidual membranes and placenta.


Menstruation. - The periodic changes that accompany the phenomenon of menstruation form a cycle which occupies twenty-eight days. This period is divisible into four phases ; .


1. Tumefaction (six days). The uterine mucosa thickens both because of vascular congestion and cellular multiplication. Blood escapes from the enlarged capillaries and forms subepithelial masses. The uterine glands elongate and their deeper portions especially are convoluted and dilated with secretion. The mucosa thus shows a superficial, compact layer and a deep, spongy layer.


2. Menstruation proper (four days). The superficial blood vessels rupture and add to the blood and glandular discharge which is escaping into the uterine cavity. The surface epithelium and a portion of the underlying tissue may or may not be desquamated.

3. Restoration (five days). The vascular engorgement disappears. Extravasated blood corpuscles are resorbed or cast off. The epithelium, glands, and capillaries are repaired.


4. Intermenstruum (thirteen days). An interval of rest. Since ovulation occurs most often postmenstruum, Grosser believes that the embryo reaches the uterus during the premenstrual stage. The congestion and loosening of the uterine tissue at this time would seemingly favor the implantation of the embryo, and the glandular secretion might afford nutriment for its growth until implantation occurred. The first phase of menstruation, according to this view, prepares the uterine mucosa for the reception of the embryo. If pregnancy supervenes, it soon inhibits any further premenstrual changes so that menstruation does not occur. Menstruation proper would then represent an over-ripe condition of the mucosa and the abortion of an unfertilized ovum.

The Deciduae. - The intimate fusions between fetal and maternal tissues necessitate an extensive sloughing of the uterine lining at birth.



Fig. 50. - Vertical section through the decidua vera of about seven months, with the attached membranes in situ (Schaper in Lewis and Stohr). X 30.


The mucosa of the pregnant uterus is, therefore, designated the decidua. Its preparation and continuance during gestation, and the long deferred loss and repair at parturition, only exaggerate the events of an ordinary menstrual cycle. The two processes show undoubted fundamental similarities.


The chorionic vesicle lies embedded in part of the uterine wall only (Fig. 49). This allows three regions to be recognized : (i) a portion not in direct contact with the ovum, the decidua vera; (2) a portion which constitutes a superficial covering or arching dome, the decidua capsularis; (3) a portion underlying the embryo and between it and the muscularis, the decidua basalis.


Decidua Vera. - The premenstrual, superficial compact layer and deep spongy layer are still further emphasized in pregnancy (Fig. 50). The compact layer contains the straight but dilated segments of the uterine glands. Its surface epithelium disappears by the end of the third month. The spongy layer is characterized by the greatly enlarged and tortuous portions of the glands of pregnancy.


A prominent constituent are the decidual cells that occur chiefly in the stratum compactum (Fig. 50). They are modified stroma cells, frequently multinucleate, which become about 50^ in diameter. Athough diagnostic of pregnancy their function is in doubt. Many degenerate during the later months.


Fig. 51. - Diagrammatic section through a pregnant uterus of two months (Thomson). c, Uterine tube; c', mucous plug in cervi.x; dv, decidua vera; dr, decidua capsularis; ds, decidua basalis; ch, chorion (its longer villi constitute the chorion frondosum) ; am, amnion; u, umbilical cord; al, allantois; y,y', yolk sac and stalk.


During the first two months of gestation the long axes of the glands are vertical. Later, as the decidua is stretched and compressed, owing to the growth of the fetus, the glands are broadened and shortened, and their cavities become elongated clefts parallel to each other and to the surface of the decidua (Fig. 50). Similarly, the gland cells stretch, and flatten until they resemble endothelium. The decidua vera attains a maximum thickness of about i cm., but in the latter half of pregnancy pressure causes it to thin and lose much of its early vascularity. The cervix uteri does not form a decidua; its glands secrete a mucous plug which closes the uterus until the beginning of labor (Fig. 51).


Decidua Capsularis . - In the earlier stages of development, glands and lilood vessels occur in its substance and the surface epithelium is continuous with that of the decidua vera (Fig. 49). As the chorion expands, the capsularis grows thin and atrophic. During the fourth month it comes into contact with the decidua vera, with which it fuses, thereliy obliterating the uterine cavity (Figs. 51 and 55). Soon after, the capsularis degenerates and disappears. This allows the chorion Ireve to become adherent to the decidua vera (Fig. 50).


Decidua Basalis - During the first four months of pregnancy this portion of the mucosa resembles the decidua vera in structure (Fig. 49). Both compact and spongy layers are represented, although there are superficial erosions and blood extravasations caused by the activity of the chorionic trophoderm. The decidua basalis does not share in the degeneration common to the other deciduae but persists until birth as a component of the nutritional organ termed the placenta (Figs. 52 and 55). The decidua is said to help in preventing excessive hemorrhage during the earlier part of pregnancy by acting as a dam between the chorionic villi and the eroded uterus (p. 58).


The Placenta

The placenta has a double origin. The chorion frondosum is the fetal portion and the decidua basalis is the maternal contribution (Fig. 49). The area of persistent frondosum villi is somewhat circular in form, so that the placenta becomes disc-shaped (Fig. 56). Near the middle of its fetal surface is attached the umbilical cord ; the surface itself is covered by glistening amnion that has fused with the subjacent chorion (Fig. 52).


The Placenta Fetalis. - The villi of this portion of the chorion form profusely branched, tree-like structures which lie in the intervillous spaces (Figs. 52 and 54). The ends of some of the villi are attached to the wall of the decidua basalis and are known as anchoring villi, in contrast to the floating free villi. In the connective-tissue core of each villus are commonly two arteries and two veins (branches of the umbilical vessels), cells like lymphocytes, and special ceils of Hofbauer apparently phagocytic in function. Lymphatics are also present. The epithelium of the villi is at first composed of a layer of trophectoderm, with the outlines of its cuboidal cells sharply defined (Fig. 53 A). This layer (of Langhans ) forms and is covered by a syncytium, the trophoderm. In the later months of pregnancy, as the villi grow, the trophectoderm is used up in forming the syncytium, so that at term the trophoderm is the only continuous epithelial layer of the villi (Fig. 53 B). About the margin of the placenta the trophectoderm persists as the closing ring, which is continuous with the epithelium of the chorion Ireve.


The Plaecnta Materna. - This, like the decidua vera, is differentiated into a basal plate, which is the remains of the compact layer and forms the floor of the intervillous spaces, and into a deep spongy layer (Figs. 52 and 54 ) 1 he basal plate is composed of a connective-tissue stroma, containing decidual cells, canalized fibrin, and persisting portions of the epithelium of the villi. The - canalized fibrin - (Fig. 47) forms chiefly by a fibrinoid necrosis of the mucosa, but the fibrin of the maternal blood and the chorionic trophoderm also participate (Mall, 1915). Septa extend from the basal plate into the intervillous spaces but do not unite with the chorion frondosum (Grosser). Near term, these constitute the septa placentae (Fig. 54) which incompletely divide the placenta into lobules, or cotyledons (Fig. 56 B).



Fig. 53. - Transverse sections of chorionic villi (Schaper in Lewis and Stohr). A, At the fourth week; B, C, at the end of pregnancy.



The maternal arteries and veins pass through the basal plate, taking a sinuous course and opening into the intervillous spaces (Fig. 54). Near their entrance they proceed obliquety and lose all but their endothelial layers. The original openings of the vessels into the intervillous spaces were formed during the implantation of the ovum when their walls were eroded by the invading trophoderm of the villi (Fig. 47). As the placenta increases in size, the vessels grow larger. The ends of the villi frequently are sucked into the veins and interfere with the placental circulation.



Fig. 54. - Scheme of placental circulation (Kollmann). Arrows indicate the blood flow in the intervillous spaces.


At the periphery of the placenta is an enlarged intervillous space that varies in extent but never circumscribes the placenta completely. This space is the marginal sinus through which blood is carried away from the placenta by the maternal veins (Fig. 55). The blood of the mother and fetus does not mix, although the epithelial cells of the villi are instrumental in transferring nutritive substances to the blood of the fetus and in eliminating wastes from the fetal circulation into the maternal blood stream of the intervillous spaces.


Mall (1915) states that there is little evidence of an actual intervillous circulation; the decidua and trophoderm are active in preventing this (pp. 58 and 62). Some authorities hold that the intervillous circulation is peculiar to the second half of pregnancy. In summary, Mall regards the entire question as still open.


Parturition

Before birth, the placenta is concave on its amniotic surface, its curvature corresponding to that of the uterus (Fig. 55). At term, the duration of which is taken as ten lunar months, the muscular contractions of the uterus, termed - pains, - bring about a dilation of the cervix uteri, the rupture of the amnion and chorion lasve, and cause the extrusion of the child. With the rupture of the membranes the amniotic liquor is expelled, but the fetal membranes remain behind, attached to the deciduae. The pains of labor begin the detachment of the decidual membranes, the plane of their separation lying in the spongy layer of the decidua basalis and decidua vera, where there are only thin-walled partitions between the enlarged glands (Figs. 50 and 52). Following the birth of the child, the tension of the umbilical cord and the - after pains - which diminish the size of the uterus normally complete the separation of the decidual membranes from the wall of the uterus. The uterine contractions serve also to diminish the size of the ruptured placental vessels and prevent extensive hemorrhage. From the persisting portions of the spongy layer and from the epithelium of the glands are regenerated' the tunica propria, glands, and epithelium of the uterine mucosa.



Fig. 56. - Mature placenta (Heisler). A, Entire fetal surface with membranes attached to its periphery; B, detail of maternal surface showing cotyledons.




Fig. 55. - Section of the uterus, illustrating the relation of an advanced fetus to the placenta and membranes (Ahlfeld).


PARTURITION .


The decidual membranes, and the structures attached to them when expelled, constitute the - after birth. - The placenta is disc-shaped, about 17 cm. in diameter, 2 cm. thick, and weighs 500 gm. It is usually everted so that its amniotic surface is convex, its maternal surface concave (Fig. 56). The placenta is composed of the amnion, chorion frondosum (chorionic villi with intervillous spaces divided incompletely by the septa into cotyledons), and includes on the maternal side the basal plate and a portion of the spongy layer of the decidua basalis (Fig. 52). Near the center is attached the umbilical cord, and at its margins the placenta is continuous with the decidua vera and the remains of the chorion Iseve and decidua capsularis. The amnion lines all the deciduae (Fig. 55).


Gross Changes in the Uterus. - During pregnancy the uterus enlarges enormously, due chiefly to the hypertrophy of its muscle fibers, and the fundus reaches the level of the xiphoid process. After birth, it undergoes rapid involution; at the end of one week it has lost one-half its weight, and in the eighth week the return is complete. The mucosa is regenerated in two or three weeks from the remains of the spongy layer (Fig. 52).


Position of the Placenta and Its Variations. - The position of the placenta is determined by the point at which the embryo is implanted. In most cases it is situated on either the dorsal or ventral wall of the uterus. Occasionally it is lateral in position, and, very rarely, it is located near the cervix and covers the internal os uteri, constituting a placenta prcBvia. A partially or wholly duplicated placenta, or accessory {succenturiate) placentas may be formed from persistent patches of villi on the chorion lseve.


Ectopic Pregnancy. - If the ovum becomes implanted and develops elsewhere than in the uterus, the condition is known as an extra-uterine, or ectopic pregnancy. The commonest site is the uterine tube, tubal pregnancy. Attachment to the peritoneum, abdominal pregnancy, and the development of an unexpelled ovum within the ruptured follicle, ovarian pregnancy, are known also.


Plural Pregnancy. - Twins occur once in 85 births; triplets, once in 7000; quadruplets, once in 750,000. Each member of ordinary double-ovum - twins - (p. 42) has its own amnion, chorion, and umbilical cord. The placenta and decidua capsularis are also individual, except in those cases where the original proximity of implantation leads to secondary fusions. Single-ovum, identical twins comprise only 15 per cent of the entire twin group; the chorion, placenta, and decidua capsularis are necessarily common, but the cord and usually the amnion are double.


CHAPTER IV . AGE, BODY FORM AND GROWTH CHANGES AGE. SIZE AND WEIGHT OF EMBRYOS


The age of a human embryo can not be determined with certainty, because too little is known of the time relations existing between ovulation and menstruation, and between ovulation, coitus, and fertilization (p. 27). This lack of a reliable basis makes any computation approximate, although the errors thus introduced are significant only in young specimens.


From numerous clinical observations it is certain that ovulation does not immediately precede menstruation, as was long held, but on the contrary follows it (p. 24). Experience proves that most pregnancies date from a coitus within a week or ten days after the menses cease. Hence, it is a])proximately correct to compute the age of an embryo from the tenth Jay after the onset of the last menstruation.


Careful studies on embryos which were accompanied by adequate data as to menstruation, coitus, and clinical history have led to the establishment of certain age-norms. By comparing a given specimen with such standards its age can be determined with reasonable accuracy. It is simplest to make these comparisons on the basis of size, although young embryos vary sufficiently so that structure must be taken into account as well. Embryos are measured in two ways. Commonest is the crown-rump length (designated CR), or sitting height; this is the measure from vertex to breech. The second is the crown-heel length (CH). or standing height.

The following table, based on data by Mall and Scammon, lists the size and weight of human embryos corresponding to definite ages : Ratio of increase .

.


Crown-rump length .

Crown-heel length .

.

to weight at .

.

(.CR), or sitting .

(CH). or standing .

Weight in .

beginning of .

Age .

height (mm.).

. height (mm.) .

grams .

month .

Three weeks .

0.5 .

0.5 .

.

.

Four weeks .

2.5 .

2-5 .

.

8000.00 .

Five weeks .

5-5 .

5-5 .

. 004 .

.

Six weeks .

I I . 0 .

11.0 .

.

.

Seven weeks .

17.0 .

19 . 0 .

.

.

Second lunar month .

25.0 .

30. 0 .

2 .

499 . 00 .

Third lunar month .

68.0 .

98 . 0 .

24 .

I I . 00 .

Fourth lunar month .

I 2 I . 0 .

180.0 .

120 .

4.00 .

Fifth lunar month .

167 . 0 .

250.0 .

330 .

1-75 .

Sixth lunar month .

210.0 .

3130 .

600 .

0.82 .

Seventh lunar month ,.

. 245 . 0 .

370.0 .

1000 .

0.67 .

Eighth lunar month .

284.0 .

425 0 .

1600 .

0.60 .

Ninth lunar month .

316.0 .

470.0 .

2400 .

0.50 .

Tenth lunar month .

345 â–  0 .

500. 0 .

3200 .

0.33 .


68 .



For estimating the age of an embryo when its size is known, or the reverse, the following rules are useful ;

Standing height (in cm.) X 0.2 = Age {in months)

Sitting height (in cm.) X 0.3 = ,-lg^ {in months) (For embryos less than 10 cm. long, add one month to the result)

Age (in months) ^ 0.2 = Standing height (in cm.)

Age {in months) -u 0.3 = Sitting height {in cm.) (For embryos of the first 3 months, subtract 4 cm. from the result)

Of practical interest is the determination of the date of delivery of a pregnant woman. Most labors occur ten lunar months, or 280 days, from the first day of the last menstrual period. The month and day of this date are easily found by counting back three months from the first day of the last period, and then adding one week. As some women menstruate once or more after becoming pregnant this computation is not infallible.


For comparison and reference, the gestation periods of a few representative mammals are appended ;

Opossum 13 days Pig Mouse 20 days Sheep Rat 21 days Cow Rabbit 30 days Horse Cat 8 W - eeks Rhinoceros Dog, guinea pig 9 weeks Elephant . .



The early history of the human ovum, including implantation and the development of membranes for its protection and nutrition, has been described on previous pages. The present section will deal with the appearance of the embryo and fetus at successive stages of uterine existence.


Period of the Embryo

Embryos of the Second Week. - The youngest known embryo is the Miller specimen. It is somewhat like the diagram represented in Fig. 40 A. The central embryonic anlage is solid, without amnion cavity or yolk sac; it measures oI mm. in length. The extra-embryonic mesoderm is unsplit by a coelom. The chorion has both syncytial and Langhans layers, but true mesodermal villi are absent; its internal cavity' measures 0.44 mm.

The Bryce-Teacher ovum (Fig. 40 B) differs from the foregoing specimen chiefly by possessing an amniotic cavity^ and y'olk sac.


A well-defined extra-embryonic coelom divides the mesoderm of Peter - s specimen into somatic and splanchnic layers, and there is also the beginning of true villi (Figs. 40 C and 46). The ectodermal embryonic disc measures 0.19 mm.; it is thickened and separated from the entoderm by a layer of mesoderm (Fig. 41). Strands of mesoderm, known as the magma reticulare, bridge the extra-embryonic body cavity, which is 0.9 X 1.6 mm. in diameter (Fig. 41).


17 weeks 21 weeks 41 weeks 48 weeks 18 months 20 months .


These ova all belong to the latter part of the second week. The yolk sac is smaller than the amnion and the villi are mostly unbranched. The embryo is merely a plate combined from the three germ layers. Neither primitive streak nor allantois has appeared. Even in the oldest, a broad zone of mesoderm connects embryo to chorion.


Embryos of the Third Week. - The Mateer ovum is shown as Fig. 32 A. It possesses a distinct primitive groove and allantois. The embryonic disc is 0.9 mm. in length.


Fig. 57 - Dorsal view of a human embryo of 1.54 mm. (Spee). X 23.


A head process with its contained notochordal canal features the advance illustrated by the Ingalls embryo (Fig. 32 B). There is also the beginning of a neural groove. The chorionic vesicle has an internal diameter of 7 mm.


Spec’s specimen has progressed still further (Fig. 57). The embryonic disc measures 1.54 mm. and is slightly constricted from the yolk sac. The primitive streak is confined to the caudal end of the embryonic disc, the neural folds are well-marked, and a neurenteric canal opens as a pore into the primitive intestinal cavity. In longitudinal section it is evident that the floor of the head process has disappeared, leaving its roof as the notochordal plate (Figs. 40 D and 43). The fore-gut is forming and there are indications of a future heart anlage.


In this group as a whole, the continued extension of the extra-embryonic coelom has separated the embryo from the chorion except in the region of the body stalk, which constitutes a bridge that contains the allantois. The yolk sac is now larger than the amnion. The chorionic villi branch freely and there is evidence of blood-vessel formation in the wall of the yolk sac (Fig. 43), and, usually, in the body stalk and chorion.


Embryos of the Fourth Week. - Embryos of this period are early characterized by the presence of high neural folds (Fig. 58) whose edges soon unite along part of their extent to form a tube which is the anlage of the brain and spinal cord (Figs. 59 and 245). The expansive brain portion is already recognizable. The mesoderm of each side of the midplane becomes arranged in blocks, the primitive (mesodermal) segments, visible externally.

In the embryo shown in Fig. 245 there are 14 pairs. The primitive streak is now insignificant (Figs. 44 and s8).


Fig. 58. - Kromer human embryo of 1.8 mm., in dorsal view (after Keibel and Elze). X 20.


Fig. 59. - Human cmbrjm of 2.1 1 mm. in dorsal view (Eternod). X 35.


Growth at the head and tail regions appears to constrict the embryo from the yolk (Figs. 58 and 245). In a longitudinal section of an embryo at the middle of this period (Fig. 44), both fore- and hind-gut are evident and the heart is conspicuous. A system of blood vessels is established connecting with the heart (Figs. 180 and 181). The embryo is now cylindrical, its body wall encloses two more or less complete tubes (neural and enteric) with the axial notochord between. During this period there is an increase in length from 0.5 to 2.5 mm.


Embryos of the Fifth Week. - Specimens corresponding to Figs. 60 and 61 stand at the turn between the fourth and fifth weeks, whereas one like Fig. 62 is more representative of this period. The progressive separation of embryo from yolk sac is evident. The primitive segments have increased until the 2.6 mm. specimen (Fig. 61) has 35 of the definitive 38 pairs. The convex curvature of the back is characteristic. External swellings indicate the three primary brain vesicles and the head becomes hexed at a right angle in the mid-brain region. On each side of the future neck appear branchial arches, separated by grooves. The hrst pair of arches bifurcates into maxillary and mandibular processes that will form the upper and lower jaws; between them is a depression, the oral fossa or stomodeum, where the mouth will be. The heart is large and flexed. The body ends in a blunt tail, and, toward the end of the period, bud-like outgrowths indicate the anlages of the upper and lower limbs. An idea of the extent of internal organization may be gained by examining Figs. 91, 183 and 184.


Embryos of Six to Eight Weeks. - These embryos range between 5.5 and 25 mm. and show marked changes. Their external form comes to resemble more the adult condition, and, after the second month, the developing young is designated a fetus. This external metamorphosis may be followed by referring to the illustrations of embryos of 7 mm. (Fig. 63), 9 mm. (Fig. 227), 12 mm. (Fig. 64), 18 mm. (Fig. 65), and 23 mm. (Fig. 66; two months). It is due principally to the following factors: (i) Changes in the flexures of the body; the dorsal convexity is lost, the head becomes erect, and the body straight. (2) The face develops (also illustrated in Fig. 68). (3) The external structures of the eye, ear, and nose appear. (4) The prominent tail of the sixth week regresses and becomes inconspicuous, largely through concealment by the growing buttocks. (5) The umbilical cord encloses both yolk stalk and body stalk and constitutes the sole attachment, limited to the region of the umbilicus. (6) The heart, which formed the chief ventral prominence in earlier embryos, now shares this distinction with the rapidly growing liver, and the two determine the ventral body shape until the eighth week when the gut dominates the belly cavity and the contour of the abdomen is more evenly rotund. (7) The appearance of a neck region, due chiefly to the settling of the heart caudad and the loss of the branchial arches. (8) The external genitalia appear in their - sexless - condition.


Fig. 62. - Human embryo of 4.2 mm. (His). X 15.


Fig. 63. - Human embryo of 7 mm. (Mall in Kollman). X 14. 1, u, HI, Branchial arches; u, lit., heart; L, liver; 0, otic vesicle; R, olfactory placode.


Fig. 64 . - Human embryo of 12 mm. (Prentiss). X 4 .



Period of the Fetus


During the third month the fetus definitely resembles a human being, but the head is still disproportionately large (Fig. 66); the umbilical herniation is reduced by the return of the intestine into the abdomen; the eyelids fuse, nail anlages form, and sex can now be distinguished readily. In the fourth month, the muscles become active and cause fetal movements; lanugo hair makes its appearance (Fig. 66). At five months, hair is present on the head. During the sixth month the eye brows and lashes grow and vernix caseosa forms; the body is lean but in better proportion. At seven months, the fetus looks like a dried-up, old person with red, wrinkled skin; the eyelids reopen. In the eighth month, the testes usually are in the scrotum ; infants of this age born prematurely may generally be reared. In the ninth month, the dull redness of the skin fades, wrinkles smooth out, the panniculus adiposus develops, the limbs become rounded, and nails extend to the finger tips. At ten months, the child is - at full term, - ready to cope with an extrauterine existence (Fig. 55).


Fig. 65. - Human embryo of 18 mm. with its membranes. X 2. The chorion is opened and reflected; the upper half of the amnion has been cut away.


Fig. 66. - Human embryos of three weeks to two months (His), and fetuses of three and four months (De Lee). Natural size.


+++++++++++++++++++++++++++++++++.

THE ESTABLISHMENT OF EXTERNAL FORM


Although the preceding section deals largely with the aquisition of fetal form, this topic requires supplementary treatment.

The Head and Neck Since development in the cephalic region maintains its early advantage, the head and neck of an embryo are for a long time disproportionate^ large. In Fig. 63 the last cervical segment is midway on the body. The gradual adjustment of size relations may be traced in Fig. 6g .


Anomalies. - Many grossly abnormal embryos are found at operation or spontaneous abortion. Various pathological conditions in the embryo commonly accompany those disturVjances which induce its stunting or death. Degenerative changes are common also in the fetal membranes, although the chorionic sac sometimes continues to grow quite normally after the embryo has died or disappeared. Dead, retained fetuses are usually resorbed, but they may mummify and persist indefinitely,


The head is composed of two portions almost from the start. One is neural in nature and includes the brain, eyes, and internal ears, and their supporting structures. The other is the facial, or visceral, part that contains the cephalic ends of the alimentary and respiratory tracts. The neural portion is much the larger in young embryos and this superiority is never lost completely, although the subsequent differentiation and growth of the nose, jaws, and pharynx reduces the early disparity.

Branchial Arches. - -The formation of the face and neck involves the history of the branchial arches. These are bar-like prominences, separated by grooves, which occur on the lateral surfaces of the neck (Figs. 6 1 to 63). They correspond to the gill-bearing arches of fishes that are separated by clefts through which respiratory water flows. In amniotes they never assume a respiratory function, but occur as transitory vestiges that are applied to various purposes, then disappear. The human embryo develops five such arches, separated by four ectodermal grooves; subjacent to these grooves the entoderm of the pharynx bulges correspondingly (Fig. 87). The thin plates thus formed by the union of ectoderm and entoderm sometimes rupture to make temporary openings, reminiscent of the gill-slit condition.


The last arch lies caudal to the fourth cleft and is poorly defined along its posterior margin. Toward the end of the sixth week, the first and second arches overlap the other three and obScure them. Fig. 63 shows the beginning of this process. Fig. 227 an advanced stage, and in Fig. 64 it is complete. The caudal arches sink into a triangular depression called the cervical sinus. When the posterior edge of the second arch fuses with the thoracic wall, the sinus and its contained arches are closed off. This cavity eventually degenerates.


Various muscles and bones form from the arches, and from the entodermal pouches certain glandular organs arise. The completion of this metamorphosis marks the appearance of a neck (Fig. 65) which is characteristic of amniotes alone.


Anomalies. - Imperfect closure of the branchial clefts (usually the second) leads to the formation of cysts, diverticula, or even fistulae. Such structures may be derived either from an ectodermal groove or the complementary entodermal pouch.


The Face. - Pig embryos show clearly how the face forms. In Fig. 369 the expansive jronto-nasal process represents much of the front of the head. The olfactory pits are present, and the first branchial arches have not only bifurcated into maxillary and mandibular processes but the mandibular segments have already united as the lower jaw. Laterally, the olfactory pits subdivide the fronto-nasal process into paired lateral and median nasal processes (Figs. 394 and 67 A). Soon, the median nasal processes fuse with each other and with the maxillary processes; this constitutes the upper jaw (Fig. 67 B). The lateral nasal processes likewise join the maxillary process, thereby obliterating the lacrimal groove, and forming the wings and margins of the nose and the adjacent cheek region. Meanwhile, the mesial portion of the original fronto-nasal process becomes the forehead and the septum and bridge of the nose.


The early development of the human face is essentially the same. These changes may be followed in Fig. 68. At first the nose is broad and fiat, with the nostrils set far apart and directed forward (Fig. 68 C). In the later fetal months the bridge is elevated and prolonged into the apex, and the nostrils look downward (Fig. 68 D). The line of fusion of the median nasal processes is evident in the adult as the philtrum . The chin is a median projection from the fused mandibular processes. During the formation of the jaws the originally broad mouth opening is reduced in its lateral extent. Epithelial ingrowths begin to separate the lips from the alveolar portions of the jaws at the fifth week (Fig. 79); at birth the inner edges of the lips bear numerous villosities. Progressive modelling of the face continues until the individual becomes fully grown.



Fig. 67. - Development of the pig - s face (Prentiss). X 7. A, 12 mm.; B, 14 mm.



Anomalies. - A common facial defect is hare lip. This is usually unilateral and on the left side. It may involve both lip and maxilla. Hare lip is attributed to the failure to fuse of the median nasal and maxillary processes (Kdlliker), or the lateral and median nasal processes (Albrecht).


Fig. 68. - Stages in the development of the human face (adapted). A, Five weeks; B, six weeks; C, eight weeks; D, si.xteen weeks. The fronto-nasal process is indicated by parallel lines, the median nasal processes by circles, and the lateral nasal processes by dots.


The Sense Organs. - The eye, ear, and nose will be considered in detail in Chapter XV. The external nose has just been described. The eye makes its appearance in the early weeks, and, by the second month, lids are present. For a time the e^-es are placed laterally and far apart, but gradually this distance is reduced (Fig. 68). The external ear is developed around the first branchial groove by the appearance of small tubercles which form the auricle (Figs. 64, 65 and 31 1). The groove itself becomes the external auditory meatus.


The Trunk

In young embryos the trunk is like a cylinder, flattened by lateral compression (Fig. 63). Its external contour is determined by the modelling of the viscera within. During the fetal period, this visceral mass becomes more rounded and the muscles and skeleton of the trunk appear, d'he trunk then assumes an ovoid form, circular in section, and largest at the umbilicus (Fig. 66). From the third fetal month through early infancy there is relative!}^ little change in the trunk ])roportions. When erect i)osture is assumed, the dominance of the thorax and abdomen is reduced and the lumbar region gains in prominence and relative length. The thorax of the newborn is rather conical, with its base below, due to the ril:)s l)cing more horizontal. In the adult the thorax is barrel-shaped, that is, broadest in its middle. The characteristic curves of the spinal column are absent at birth. They appear partly through the drag of body weight, ])artly through the pull of the muscles, and are not pronounced until the posture becomes erect.


Anomalies. - The embryonic tail sometimes persists and develops beyond its ordinary size. Specimens as long as 8 cm. have been recorded in the newborn. Most are soft and ileshy, but a few have contained skeletal elements. Some tumors of the coccygeal region are attributed to the activity of residual primitive-streak tissue.


The Appendages

The limbs appear during the fifth w^eek as lateral buds. In a 4 mm. embryo (Fig. 62) limb buds may be recognized, but due to the early expanse of the head-neck region they seem to be located far down the body. The distal ends flatten (Fig. 63) and a constriction divides this paddle-like portion from the proximal, rounded segment (Fig. 196). Later, a second constriction separates the cylindrical part into two further segments (Figs. 64 and 65), and the three divisions of arm, forearm, and hand, or thigh, leg, and foot are respectively formed. Radial ridges, separated by grooves, first foretell the formation of digits (Figs. 64 and 65). These elongate as the definitive fingers and toes, and rapidly project beyond the original plates; the latter by a slower rate of growth become confined as webs about the basal ends of the digits (Fig. 66). The thumb and great toe early separate widely from the index finger and second toe.


The limbs as a whole undergo several changes of position. At the very start they point caudad (Figs. ig6 and 64), but soon project outward at right angles to the bod\^ wall. Next, they are bent ventrad so that the thumb (radial) side of the arm and the great toe ( tibia!) side of the leg are directed forward; the palmar and plantar surfaces face the body; the elbow turns outward and somewhat caudad, the knee outward and slightly cephalad (Fig. 65). Finally, both sets of limbs undergo a torsion of 90° about their long axes, but in opposite directions. As a result, the radial side of the arm is outward (when radius and ulna are parallel) and the palm faces ventrad; on the contrary, the tibal side of the leg is the inner side, while the sole faces dorsad. By following through these changes it will be seen that the radial and tibial sides of arm and leg are homologous, as are palm and sole, elbow and knee.


The upper limb buds arise first and they maintain a slight advance in differentiation. Not until the second year of childhood are the two equal in length.


Anomalies. - The extremities may either fail to develop, or become mere stubs; the hands and feet may join the body like flippers. Rarely, the hands or feet are partially duplicated or reduced. The presence of extra digits is polydactyly; a fusion of digits constitutes syndactyly. More or less complete union of the legs occurs as sympodia.


The developmental period of man is divided by the incident of birth into prenatal and postnatal periods. At birth the infant is sufficiently advanced to be cared for outside its mother - s body, yet its development is far from complete. In its new environment differentiation and growth, especially marked by changes in form and proportion, continue until the beginning of the third decade ; only then is full size and mature structure attained.


The several divisions of the developmental period are listed as follows by Scammon, from whose account much of the material of the succeeding paragraphs is taken : .


Divisions of the Develop.mental Period in Man ^Period of the ovum (Fertilization to end of second week) Prenatal life - Period of the embryo (Second to eighth week) \Period of the fetus (Second to tenth month) Birth Period of the newborn (Neonatal period; birth to end of second week) 1 Infancy (Second week until assumption of erect posture at 13 to 14 months) j 1 Early childhood (Milk-tooth period; first to sixth year) j - idliood childhood (Sixth to ninth or tenth year) ” \ Later childhood (Prepubertal period; from 9 or 10 years to 12-15 Postnatal life ! I years in females and 13-16 years in males) I Puberty I (Fourteenth year in females: sixteenth year in males) I Adolescence (From puberty to the last years of the second decade in females I and to the first years of the third decade in males) .


Changes in Form. If an adult maintained the chubby newborn shape his weight would be twice the actual amount. Fig. 69 shows the proportions of the body at various developmental periods, all drawn as of the same height. Note: the great decrease in the size of the head; the constancy of the trunk length; the early completion of the arms and the tardier growth of the legs; the upward shift of the umbilicus and symphysis pubis, and the downward trend of the midpoint of the body.


Fig. 6g. - DiagramS to illustrate the changing proportions of the body during prenatal and postnatal growth (Scammon after Stratz).


Certain of these facts may be tabulated in terms of per cent of the total body volume:

Growth in Relative Volume of the Parts of the Body .


In per cent of the total body volume .


Age .

Head and neck .

Trunk .

Arms .

Legs .

Second fetal month .

45 .

50 .

3 .

3 .

Sixth fetal month .

37 .

40 .

8 .

15 .

Birth .

27 .

49 .

9 .

15 .

Two years .

22 1 .

50.5 .

9 .

17-5 .

Six years .

15 .

51 .

9 .

25 .

^Maturity .

7 .

53 .

10 .

30 .


Increase in Surface Area. - The relation of surface area to body mass or volume has a profound influence on metabolism. This relation changes greatly during the postnatal period. At birth, the surface area is about 2500 sq. cm. This is doubled in the first year, tripled by the middle of childhood, and increases rapidly before puberty. At maturity, the total gain is seven-fold. Since, however, the weight of the body has increased some twenty-fold in the same time it is obvious that there has been a relative loss. Thus, in the newborn there are over 800 sq. cm. per kilogram of body weight, whereas in the adult there are less than 300 sq. cm.


Growth in Weight. - During prenatal life the weight of the body increases several billion times, whereas from birth to maturity the increment is only twenty-fold. In absolute mass, however, 95 per cent of the final weight is acquired after birth. The ratio of increase during each fetal month to the weight at the beginning of that month is shown in the table on p. 68.


Growth in Length. - Growth in length and in weight have certain features in common, although the relative increase in length is obviously smaller since weight is a three dimensional phenomenon. The increase in the second fetal month is ten-fold but thereafter the relative rate of growth gradually declines. The data of prenatal growth are given in the table on p. 68. The total postnatal increment is 3.3 times. During the first six months after birth, length increases 30 per cent; in the first year, 50 per cent. Throughout the most of childhood the linear increase is very slow, but at the prepubertal period there is an acceleration; as with weight, this is begun and ended earlier in girls than in boys. Growth is complete at about 18 years in females and soon after 20 in males. The body is heaviest in proportion to its length during late fetal life and early infancy. From the middle of the first year until after puberty there is a decline in relative weight. Thereafter there is an increase in relative mass which may continue throughout life. During infancy and childhood girls are relative^ lighter than boys, but after puberty the reverse is true.


Growth of Organ Systems. - The skeleton grows rather slowly until the ninth and tenth fetal months, when it shows an acceleration. At birth, it constitutes from 13 to 20 per cent of the body weight. Postnatal growth apparently parallels that of the body as a whole and shows neither relative loss nor gain. The musculature likewise grows slowly at first, but forms about 2 5 per cent of the weight of the newborn and 40 to 45 per cent of the adult. The central nervous system, on the contrary, is relatively huge in the young embryo. It decreases from about 25 per cent in the second month to about 15 per cent at birth and 2 to 2.5 per cent in the adult. Incomplete data on the peripheral nervous system and skin indicate a considerable reduction in relative weight during the postnatal years. As a whole, the visceral group decreases slowly and steadily in relative weight after the first two embryonic months. In the second month they comprise about 15 per cent of the body weight, about 9 per cent at birth, and from 5 to 7 per cent in the adult.


Growth of the Organs. - Although the general course of relative growth in the individual organs follows that of the visceral group, each has its characteristic curve. Each usually increases more or less rapidly to a maximum relative size and then decreases in relative size through the subsequent prenatal and postnatal periods.

During fetal life the curves of absolute growth are quite similar. The various organs have an initial period of slow increase, followed after the fifth month by a terminal phase of rapid growth. However, this uniformity disappears at birth, and most of the organs can be arranged in four main divisions. The splanchnic group includes the digestive, respiratory, and urinary organs, and the heart, thyroid, and spleen. The nervous group comprises the brain, cord, and eyeballs. The genital group excludes the ovary and uterus which have special curves. The lymphoid group includes all but the spleen. Fig. 70 shows these relations graphically from embryo to adult.


Fig. 70. - Chart showing the course of growth in the various organ groups (after Scammon).

Growth is calculated in per cent of adult weight.



Anomalies. - Giants and dwarfs may be of monstrous size when born at full term, or the acceleration or slowing may be secondary at some later period. This abnormal size is sometimes unilateral or even confined to specific parts of the body.


++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

PART II. ORGANOGENESIS ENTODERMAL DERIVATIVES

CHAPTER V THE DIGESTIVE SYSTEM



The entoderm of the embryonic disc is at first directly continuous with the entodermal lining of the yolk sac, and merely forms a roof to that organ (Fig. 40 C). As the embryo grows and expands, while its connection with the yolk sac lags in development, the entoderm necessarily takes the form of a blind tube within the cylindrical body. This extends first into the head region as the fore-gut (Figs. 40 C and 43), then tailward as the hind-gut (Fig. 44). The intermediate region, open ventrally through the narrower yolk stalk into the yolk sac, is sometimes termed the mid-gut (Fig. 71), but its existence is brief for the yolk stalk loses its connection with the gut during the sixth week.


At each end, the gut comes into direct contact ventrally with the ectoderm. The plates thus formed are the pharyngeal and cloacal membranes (Fig. 71). The pharyngeal membrane forms the floor of a depression known as the oral fossa, or stomodeum ; this fossa is bounded by the fronto-nasal, maxillary, and mandibular processes (Figs. 61 and 62). At the beginning of the fifth week (2.5 to 3 mm. embryos), the pharyngeal membrane ruptures and the oral fossa and fore-gut become continuous. The oral fossa develops into the front part of the mouth cavity, which is therefore ectodermal. The remainder of the mouth cavity, the respiratory tract, and the alimentary canal to a point well along the small intestine are all derived from the entodermal fore-gut.


The caudal end of the entodermal tube comprises the cloaca, which soon receives the allantoic, urinary, and genital ducts (Figs. 87, 91 and 94). The cloaca promptly begins to subdivide into a dorsal rectum and a ventral urogenital sinus (Figs. 139 to 142). At the same time, the cloacal membrane is separatedinto anal and urogenitalmembranes (Figs. 71, 95 and 96). The anal membrane ruptures at about the ninth week, and an external depression, the proctodeum, therefore becomes continuous with the hindgut (Figs. 96 and 142). It constitutes the anal canal, which, like the front part of the mouth cavity, is lined with ectoderm. The hind-gut itself forms some of the small intestine, the colon, and the rest of the rectum (Figs. 93 to 96). It will be noticed that the primitive entodermal tube extends a little beyond the cloacal membrane (Figs. 71, 91 and 139); this tail-gut, or postanal gut, soon dwindles and disappears.

The entoderm forms only the epithelial lining of these organs. AU other coats develop from the investing splanchnic mesoderm. The original low epithelium of the gut differentiates into the several types of simple epithelium formed in the digestive and respiratory systems, as well as into the pseudostratified and stratified forms. The various glands are primarily epithelial outgrowths.


Fig. 71. - Diagrams showing the human alimentary canal in median sagittal section. X 35. A, 2 mm. (modified after His): B, 2.5 mm. (after Thompson).


It is impossible to determine the exact junction of ectoderm and entoderm in the mouth, but in general the roof and peripheral portions are ectodermal. The salivary glands are considered to be from ectoderm, as are the enamel of the teeth, a portion of the tongue epithelium, and much of the lining of the nose and palate. Although these structures do not strictly belong with entodermal derivatives, it is simplest to consider them with the systems of which they are integral parts.


THE MOUTH


Lips and Cheeks. - During the fifth week, these separate from the jaws proper by the ingrowth of epithelial plates which promptly begin to thin and form the vestibule (Figs. 74, 76 and 79).


The Palate. - -The roof of the original mouth cavity is the base of the skull. When the membranes which separate the olfactory pits from the mouth rupture, their orifices, the primitive choance, also open into the common oral cavity. The nasal passages next become separate by partitioning off a portion of the mouth cavity and adding it to their original extent. They then communicate with the pharynx by the secondary, definitive choance. The horizontal septum which thus divides mouth from nasal ^passage is the palate. The details of its formation follow ; At first the jaws are closed and the tongue extends up between shelf like folds of the maxilla, the lateral palatine processes (Figs. 73 A and 74), which project downward (Fig. 72 A). Soon the mandible drops, owing to growth changes, and the tongue is withdrawn. This allows the palatine folds to bend upward to the horizontal plane (Fig. 75), approach, and fuse (Fig. 72 B). The shift of the lateral palatine processes is an active bending, due to cellular proliferation on their under sides (Fig. 75). The union of the halves of the palate begins about the end of the second month and progresses backward toward the pharynx (Fig. 73 B). Coincidently, bone appears in the front part and forms the hard palate; more caudad, ossification fails, and this region constitutes the soft palate and its free apex the uvida. The unfused, backward prolongations of the palatine folds give rise to the pharyngo-palatine arches, which delimit oral cavity from pharynx. The palate shows a median seam, and, for a time, the uvula is notched; both are indicative of the mode of origin.



Fig. 72. - Sections through the jaws of pig embryos, to show the development of the palate (Prentiss). X 8. A, 22 mm.; B, 34 mm.


Fig. 73 - Dissections to show the development of the palate in pig embryos (Prentiss). X 5. A , The upper jaw and palatine processes of a 22 mm. embryo in ventral view; B, fusion of the palatine processes in a 35 mm. embryo.


74. - The roof of the mouth of a two-months - human embryo, groove, primitive choanse and developing palate (after His). showing the labial ,X 9 .



Fig. 75. - Section through the jaws of a 25 mm. pig embryo, to show the change in position of one palatine process due to unequal growth (Prentiss).



The median nasal lobes of the original fronto-nasal process also develop median palatine processes, so-called, which do not contribute to the palate but form the premaxillary portion of the upper jaw (Figs. 73 and 74). Fusion with the palate is incomplete and in the midplane there is a gap, the incisive foramen, flanked by the incisive canals (of Stenson). These become covered with mucous membrane, although they sometimes are patent at birth.


Fig. 76. - Early stages in the development of the teeth (Rose). . 4 , Seven weeks (X 90); B, nine weeks (X 45).


Anomalies. - The lateral palatine processes occasionally fail to unite in the middle line, producing a defect known as deft palate. The extent of the defect varies considerably, in some cases involving only the soft palate, while in other cases both soft and hard palate are cleft. It may be associated also with hare lip.


The Teeth. - The teeth have a double origin. The enamel is from ectoderm ; the dentine, pulp, and cement are mesodermal.


The Enamel Organ. - When the labial groove is forming in embryos of six weeks, a horizontal shelf develops from it and extends backward into the substance of the jaw (Fig. 76). This curved dental ridge, or lamina, is parallel with the adjacent labial groove and lies mesial to it (Fig. 82). At intervals a series of thickenings develop, the anlages of the enamel organs; these will form enamel and serve as the moulds of the future teeth (Figs. 76 B and 77). Early in the third month the ventral side of each enamel organ becomes concave, like an inverted cup, and the concavity is occupied by dense mesenchymal tissue, the dental papilla, which will differentiate into dentine and pulp (Figs. 77 and 78). An enamel organ and its associated dental papilla is the basis of each tooth (Fig. 79). Ten such anlages of the decidual, or milk teeth, are present in each jaw (Fig. 82). Their connection with the dental ridge is eventually lost.



Fig. 77. - Models of the early development of three teeth, one in section (Lewis and StohrL .


Fig. 78. - Section through an upper incisor from a fetus of three months (Prentiss). X 70.


The compact internal cells of the enamel organ transform into a reticulum resembling mesenchyme, termed the enamel pulp (Fig. 78). The outer enamel cells, at first cuboidal, flatten out as a fibrous layer. Neither of these components contributes to tooth formation. The inner enamel cells line the cup-shaped concavity of the enamel organ. Over the crown of the tooth these cells are designated amelohlasis, for they become columnar and produce the enamel layer along their basal ends (Fig. 80). The enamel is laid down first as an uncalcified, fibrillar layer which then calcifies in the form of enamel prisms, one for each ameloblast. The enamel is deposited first at the apex of the crown and then downward .


Fig. 79. - Parasagittal section through the mandible and tongue of a three-months - fetus, showing the relations of the first incisor anlage (Prentiss). X 14.


Fig. 80. - Section through a portion of the crown of a developing tooth, showing the various layers (Tourneux in Heisler).


Toward the root. The enamel cells about the future root of the tooth remain cuboidal or low columnar in form, come into contact with the outer enamel cells, and the two layers constitute the epithelial sheath of the root (Fig. 81); it does not produce enamel prisms.


The Dental Papilla - At the end of the fourth month, the outermost cells of the dental i)apilla arrange themselves as a definite layer of columnar epithelium. Since they produce the dentine, or dental bone, these cells are known as odontoblasts (Fig. 8i). When the dentine layer is deposited, the odontoblast cells remain internal to it, but branched processes from them (the dentinal fibers of Tomes) extend into the dentine and occupy the dental canalicnli (Fig. 80). Internal to the odontoblasts, the remaining mesenchymal cells differentiate into the dental pulp, popularly known as the - nerve - of the tooth. This is composed of a framework of reticular tissue in which are found blood vessels, lym.phatics, and nerve fibers. The odontoblast layer persists throughout life and intermittently lays down dentine, so that eventually the root canal may be obliterated,


Fig. 81. - Longitudinal section of a decidual tooth of a newborn dog. X 42. Above the enamel, on either side, are artificial shrinkage spaces (Lewis and Stohr).



The Dental Sac. - The mesenchymal tissue surrounding the anlage of the tooth gives rise to a dense outer layer and a more open inner layer of fibrous connective tissue. These form the dental sac (Fig. 8i). Over the root of the tooth a layer of osteoblasts, or bone forming cells, develops, and when the epithelial sheath of the enamel organ disintegrates, they deposit about the dentine an investment of specialized bone, known as the cement. Cementum contains typical bone cells but no Haversian systems. As the tooth grows and fills its alveolar socket, the dental sac.



Fig. 82. - Dental lamina and anlages of the upper milk teeth in a three-months - fetus (Rose).


Becomes a thin, vascular layer, the peridental membrane. This has fibrous attachments to both the alveolar bone and the cement and holds the tooth in place.


Eruption. - ^When the crown of the tooth is fully developed the enamel organ disintegrates, and, as the root continues to grow, the crown approaches the surface and breaks through the gum. The periods of eruption of the various milk, or decidual teeth vary with race, climate, and nutritive conditions Usually they are cut in the following sequence: .


Median Incisors sixth to eighth month.

Lateral Incisors eighth to twelfth month.

First Molars twelfth to sixteenth month.

Canines seventeenth to twentieth month.

Second Molars twentieth to thirty-sixth month.


The permanent teeth develop precisely like the temporary set. The anlages of those permanent teeth which correspond to the milk dentition arise in another series along the free edge of the dental lamina (Fig. 77 H) and come to lie mesad of the decidual teeth (Fig. 83). In addition, three permanent molars are developed on each side, both above and below, from a backward or alioral extension of the dental lamina, entirely free from the oral epithelium (Fig. 82). The anlages of the first permanent molars appear at the end of the fourth month, those of the second molars at six weeks after birth, while the anlages of the third permanent molars, or wisdom teeth, are not found until the fifth year. The permanent dentition of thirty-two teeth is then complete.


Before the permanent teeth begin to erupt, the roots of the milk teeth undergo partial resorption, their dental pulp dies, and they are eventually shed. Toward the sixth year, before the loss of the decidual teeth begins, each jaw may contain twenty-six teeth (Fig. 83). The permanent teeth are cut as follows : .

First Molars

Median Incisors

Lateral Incisors

First Premolars

Second Premolars

Canines I

Second Molars )

Third Molars (Wisdom Teeth)



seventh year, eighth year, ninth year, tenth year, eleventh year.

Thirteenth to fourteenth year, seventeenth to fortieth year.


Fig 83. - Skull of a live-year-old child, showing the positions of the decidual and permanent teeth (Sobotta-McMurrich).


The teeth of vertebrates are homologues of the placoid scales of elasmobranch fishes (sharks and skates). The teeth of the shark resemble enlarged scales, and many generations are produced in the adult fish. In some mammalian embryos, three, or even four, dentitions are present. The primitive teeth of mammals were of the canine type, and from this conical tooth the incisors and molars have arisen. Just how the cusped tooth differentiated - whether by the fusion of originally separate units, or by the development of cusps on a single primitive tooth - is debated.



Fig. 84. - Dissections showing the development of the tongue in pig embryos (Prentiss). X 12. A, 7 mm.; B, 9 mm.; C, 13 mm.


Anomalies. - Dental anomalies are frequent. They may consist in the congenital absence of some or all of the teeth, or in the production of more than the normal number. Defective teeth are frequently associated with hare lip. Cases have been noted in which, owing to a defect of the enamel organ, the enamel was wanting. Third dentitions have been recorded, and occasionally fourth molars are developed behind the wisdom teeth.


The Tongue. - The tongue develo])s as two distinct portions, the body and the root, separated from each other by a V-sha]ied groove, the sulcus tcnninalis (Fig. 85 B). In both human and pig embryos, the body of the tongue is represented by three anlages that appear in front of the second branchial arches. These are the median, somewhat triangular iuhcrculitm uupar, and the paired lateral swellings of the first, or mandibular arches - all of which are present in human embryos of 5 mm. (Figs. 84 A and 85 . 4 ). At this stage, a median ventral elevation, formed by the union of the second branchial arches, constitutes the copula. This, with the ])ortions of the second arches lateral to it, forms later the root of the tongue. Between it and the tuberculum impar is the point of evagination of the thyroid gland, represented in the adult by the foramen cecum (Fig. 85). I'he copula also connects the tuberculum impar with a rounded prominence that is developed in the midventral line from the bases of the third and fourth branchial arches. This is the anlage of the epiglottis (Figs. 84 and 85).




Fig. 85. - Stages in the development of the human tongue (adapted). A, 6 mm.; B, 15 mm. Contributions from the first three branchial arches are indicated respectively by parallel lines, dots and crosses; the tuberculum impar is marked by circles.


In later stages (Figs. 84 B, C and 85 B), the lateral mandibular anlages, bounded laterally by the alveolo-lingual grooves, increase rapidly in size and fuse with the tuberculum impar, which lags behind in development, and, according to recent investigators, atrophies completely. The epiglottis enlarges and becomes concave on its ventral surface. Caudad, and in early stages continuous with it, are two thick, rounded folds, the arytenoid ridges. Between these is the slit-like glottis, leading into the laryn.


In fetuses of 11 weeks, the fungiform and filiform papilla; may be distinguished as elevations. Taste buds appear in the fungiform papillae at 14 weeks and are much more numerous in the fetus than in the adult.



The vallate papilla: develop on a V-shaped epithelial ridge whose apex corresponds to the site of the thyroid evagination (Fig. 85 B). After the thirteenth week, circular epithelial down-growths occur at intervals along the ridges and take the form of inverted and hollow truncated cones (Fig. 86 A). During the fourth month circular clefts appears in the epithelial down-growths, thus separating the walls of the vallate papillae from the surrounding epithelium and forming the trench from which this type of papilla derives its name (Fig. 86 B). At the same time, lateral outgrowths arise from the bases of the epithelial cones, hollow out and form the ducts and glands of Ebner (Fig. 86 C). The taste buds of the vallate papillae also are formed early, appearing in embryos of three months. Foliate papilla: probably develop at about six months.


The foregoing account applies to the early origin of the mucous membrane alone. The musculature of the tongue is supplied chiefly by the hypoglossal nerve, and both nerve and muscles belong historically to the post-branchial region. If not in the development of each present-day embryo, at least in the past the musculature has migrated cephalad and invaded the branchial region beneath the mucous membrane (cf. p. 229). At the same time, the tongue may be said to extend caudad until its root is covered by the epithelium of the third and fourth branchial arches. This is shown by the fact that the sensory portions of the nn. trigeminus a.nA facialis, the nerves of the first and second arches, supply the body of the tongue, while the nn. glossopharyngeus and vagus, the nerves of the third and fourth arches, supply chiefly the root.


Fig. 86. - Diagrams showing the development of the vallate papillae of the tongue (Graberg in McMurrich). a, Valley; b, von Ebner's gland.



Anomalies. - Faulty development or incomplete fusion of the several anlages causes variable degrees of absence or bifurcation of the tongue.


The Salivary Glands. - The glands of the mouth are all regarded as derivatives of the ectodermal epithelium. They complete their differentiation only after birth.


The parotid is the first to develop. Its anlage has been observed in 8 mm. embryos, near the angle of the mouth, as a keel-like flange in the floor of the groove which divides cheek from jaw. The flange elongates, and, in embryos of seven weeks, separates from the parent epithelium, forming a tubular structure that opens into the mouth cavit\" near the front end of the original furrow. The tube grows back into the region of the external ear, branches, and forms the main body of the gland in this region, while the stem portion of the tube becomes the parotid duct. Acinus cells are present at five months.


The submaxillary gland arises at n mm. as an epithelial ridge in the groove between the jaw and the tongue, its cephalic end located near the frenulum. The caudal end of the ridge soon begins to separate from the epithelium and extend backward and ventrad into the submaxillary region, where it enlarges and branches to form the gland proper ; its cephalic, unbranched portion, persisting as the duct, soon hollows out (Fig. 79).


Fig. 87. - Diagrammatic ventral view of pharynx, digestive tube and mesonephroi of a 4 to 5 mm. embryo (adapted by Prentiss). X about 30. The liver and yolk sac are cut away. The tubules of the right mesonephros are shown diagrammatically.



The sublingual gland appears by the eighth week as several solid evaginations of epithelium from the jaw-tongue groove (Fig. 79). This group, usually regarded as a sublingual gland, really consists of the sublingual proper, with its ductus major, and of about ten equivalent alveololingual glands. Mucin cells have appeared by the sixteenth week.


Pharyngeal Pouches. - There are developed early from the lateral wall of the entodermal pharynx paired outpocketings which are formed in succession cephalo-caudad. In 4 to 5 mm. embryms, five pairs of such pharyngeal {branchial) pouches are present, the fifth pair being rudimentary (Figs. 87 and 91). Meanwhile, the pharynx has flattened and broadened, so that it is triangular in ventral view (Figs. 87 and 88).


From each pharyngeal pouch develop small dorsal and large ventral diverticula. All five pouches come into contact with the ectoderm of corresponding branchial grooves, fuse with it, and form the closing plates. Although the closing plates become perforate in human embryos only occasionally, these pouches and grooves, nevertheless, are homologous to the functional branchial clefts of fishes and tailed amphibia. The first and second pharytigeal pouches soon connect with the pharyngeal cavity through wide common openings. The third and fourth pouches grow laterad and their diverticula communicate with the pharynx through narrow ducts in lo to 12 mm. embryos (Fig. 88). When the cervical sinus (p. 77) is formed, the ectoderm of the second, third, and fourth branchial clefts is drawn out to produce the transient branchial and cervical ducts and the cervical vesicle. These are fused at the closing plates with the entoderm of the corresponding pharyngeal pouches, the fate of the entodermal pouches is varied and spectacular. Although they do not continue as parts of the digestive apparatus, their embryonic relations justify their inclusion in the present section. The first differentiates into the tympanic cavity of the middle ear and into the auditory (Eustachian) tube. The second becomes the palatine tonsil in part. The third, fourth, and fifth pouches give rise to a series of ductless glands: the thymus, parathyroids, and the ultimobranchial bodies.



Fig. 88. - Reconstruction of the pharynx and fore-gut of a 12 mm. human embryo, seen in dorsal view (Hammar-Prentiss). The ectodermal structures are stippled.



The Tonsils. - By the growth and lateral expansion of the pharynx, the second pouch is absorbed into the pharyngeal wall, its dorsal angle alone persisting, to be transformed into the tonsillar and su proton sillar fossae. Crypts arise at the end of the third month by the hollowing of solid epithelial ingrowths, whereas a mound of mesodermal lymphoid tissue hrst presses against the epithelium at the middle of the fourth month. This association constitutes the palatine tonsil.


A Subepithelial infiltration of lymphocytes during the sixth month gives rise to the median pharyngeal tonsil, which like the lingual tonsil is not of pharyngeal pouch origin. Immediately caudad is a recess, the pharyngeal bursa, formed by a protracted connection of the epithelium with the notochord (Huber). It bears no relation to the original blind termination of the fore-gut known as Seesel - s pouch. According to Hammar, the lateral pharyngeal recess (of Rosenmfiller) is not a persistent portion of the second pouch, as His asserted.


The Thymus. - The thymus anlages appear in 10 mm. embryos as ventral and medial prolongations of the third pair of pouches (Figs. 88 and 89). The ducts connecting the diverticula with the pharynx soon disappear so that the anlages are set free. At first, they are hollow tubes which soon lose their cavities and migrate caudally into the thorax, usually passing ventral to the left innominate vein. Their upper ends become attentuate and atrophy, but may persist as accessory thymus lobes. The enlarged lower ends of the anlages form the body of the gland, which is thus a paired structure (Fig. 90). At 1 1 weeks the thymus still contains solid cords and small closed vesicles of entodermal cells. From this stage on, the gland becomes more and more lymphoid in character. Its final position is in the thorax, dorsal to the upper end of the sternum. It grows under normal conditions until puberty, after which involution begins. This process proceeds slowly in healthy individuals, rapidly in case of disease. True atrophy of the parenchyma enters at about the fiftieth year.


The ventral diverticulum of the fourth pouch is a rudimentary thymic anlage which usually atrophies.

It is now generally believed that the entodermal epithelium of the thymus is converted into reticular tissue and thymic corpuscles. The latter are the atrophic and hyalinized remains of embryonic tubules and cords (Marine, 1915). The lymphoid cells were regarded by Stohr as entodermal in origin, but most observers derive them from the mesoderm.




Fig. 89. - Diagram of the pharynx and its derivatives (adapted by Prentiss). I-V, first to fifth pharjmgeal pouches.


The Parathyroid Glands. - Each dorsal diverticulum of the third and fourth pharyngeal pouches gives rise to a small mass of epithelial cells termed a parathyroid gland (Fig. 89). Two pairs of these bodies are thus formed, and, with the atrophy of the ducts of the pharyngeal pouches, they are set free and migrate caudalw^ard. The}* eventually lodge in the dorsal surface of the thyroid gland; the pair from the third pouches lies, one on each side, at its caudal border, the ]iair from the fourth pouches at the cranial border (Fig. go). Their solid bodies are broken up into masses and cords of jiolyhedral entodermal cells intermingled with blood vessels. In postfetal life, lumina may appear in the cell masses and fill with a colloid-like secretion.


Fig. 90. - Reconstruction of the thymus, thyroid and parathj-roid glands in a human embryo of two months (Tourneaux and Verdun). X 15.


The Ultimobranchial Bodies. - These bodies, also called postbranchial, are usually rated as derivatives of the fifth pharyngeal pouches (Fig. 89).


Fig. 91. - Reconstruction of a 4.2 human embryo (His- Prentiss). X 25.


By the atrophy of the ducts of the fourth pouches they are set free and migrate caudad with the parathyroids. Each forms a hollow vesicle which has been erroneously termed the lateral thyroid. It takes no part in forming thyroid tissue, but atrophies. Kingsbury (1915) denies the origin of the ultimobranchial body from any specific pouch, and asserts it is “merely formed by a continued growth activity in the branchial entoderm .


The Thyroid Gland. - In embryos with five to six primitive segments (1.4 mm.) there appears in the midventral wall of the pharynx, between the first and second branchial arches, a small outpocketing, the thyroid milage. In 2.5 mm. embryos it has become a stalked vesicle (Figs. 71 j 5 and 87). Its stalk, the thyroglossal duct, opens at the aboral border of the tuberculum impar of the tongue (Figs. 85 B); this spot is represented permanently by the foramen cecum (Fig. g6). The duct soon atrophies and the bilobled gland anlage (Fig. 89) loses its lumen and breaks up into irregular, solid, anastomosing plates of tissue as it migrates caudad. The thyroid assumes a transverse position with a lobe on each side of the trachea and larynx (Fig. 90). In embryos of eight weeks, discontinuous lumina begin to appear in swollen portions of the plates; these represent the primitive thyroid follicles. Colloid soon forms.


Anomalies. - Persistent portion of the thyroglossal duct may form cysts or even fistulce.


THE DIGESTIVE TUBE.


The several accessory coats of the digestive tube are all derived from splanchnic mesoderm wTich invests the entoderm of the primitive gut. In each division of the tube the circular muscle layer develops before the longitudinal layer.


The Esophagus. - The esophagus in 4 to 5 mm. embryos is a very short tube, extending from pharynx to stomach (Fig. 91). As the heart and diaphragm recede into the thorax, it grows rapidly in length (Figs. 95 and 96). In embryos of 8 mm. the esophageal epithelium is composed of two layers of columnar cells, but at birth they number nine or ten. The esophagus remains so broadly attached to the dorsal body wall that there is never a distinct mesentery (Fig. 124).


During the eighth week vacuoles appear in the epithelium and increase the size of the lumen, which, however, is at no time occluded. Glands begin to develop at four months. The circular muscle layer is indicated at six weeks but the longitudinal fibers do not form a definite layer until u weeks.


Anomalies. - There may be atresia. This usually involves a fistulous relation with the trachea; the esophagus is divided transversely, the trachea opening into the lower segment, while the upper portion ends as a blind sac.


The Stomach. - The stomach appears in embryos of 4 to 5 mm. as a laterally flattened, fusiform enlargement of the fore-gut, caudal to the lung anlages (Figs. 93 and 94). Its wall is composed of three layers: the entodermal epithelium, a thick mesenchymal layer, and the peritoneal mesothelium (Fig. 114). The stomach is attached dorsally to the body wall by its mesentery, the greater omentum, and ventrally to the liver by the lesser omentum (Fig. 112 B). The dorsal border of the stomach soon bulges locally to form the fundus, and also grows more rapidly than the ventral wall throughout its extent, thus producing the convex greater curvature (Fig. 92). The whole stomach becomes curved, and its cranial end is displaced to the left by the enlarging liver (Fig. 88). This forms a ventral concavity, the lesser curvature, and produces the first flexure of the duodenum.


Fig. 93. - Median sagittal section of a 5 mm. human embryo, to show the digestive canal (Ingalls-Prentiss). X 14.


The rapid growth of the gastric wall along the greater curvature also causes the stomach to rotate about a long axis until its greater curvature, or primitive dorsal wall, lies to the left, its lesser curvature, or ventral wall, to the right (Fig. 114). The original right side is now dorsal, the left side ventral in position, and the caudal, or pyloric end of the stomach is ventral and to the right of its cardiac, or cephalic end. The whole organ extends obliquely across the peritoneal cavity from left to right.


These changes in position progress rapidly and are already completed early in the second month.

The rotation of the stomach explains the asymmetrical position of the vagus nerves of the adult organ, the left nerve supplying the ventral wall of the stomach, originally the left wall, while the right vagus supplies the dorsal wall, originally the right. At the end of the seventh week the stomach has reached its permanent position, the cardia having descended through about ten segments, the pylorus through six or seven.



Fig. 94. - Reconstruction of a 5 mm. human embryo, showing the entodermal canal and its derivatives (His in Kollmann). X 25.


Gastric pits are indicated in embryos of seven weeks, and at 14 weeks the glands begin to differentiate. The gastric pits number 270,000 at birth but increase by fission to nearly seven million in the adult. At seven w'eeks, the circular muscle layer is indicated by condensed mesenchyme; a heavier ring forms the pyloric sphincter. During the fourth month the cardiac region shows a few longitudinal muscles fibers, which become distinct in the pyloric region at seven months.


The Intestine. - ^In 5 mm. embryos (Fig. 93), the intestine, beginning at the stomach, consists of the duodenum (from which are given off the hepatic diverticulum and dorsal pancreas), and the cephalic and caudal limbs of the intestinal loop, which bends ventrad and connects with the yolk stalk. Caudally, the intestinal tube expands into the cloaca. It is sup]:)orted from the dorsal body wall by the mesentery (Fig. 94).


From 5 to 9 mm., the ventral flexing of the intestinal loop becomes more marked and the attachment of the yolk stalk to it normally disappears (Fig. 95). At this stage there is formed in the caudal limb of the intestinal loop an enlargement, due to a ventral bulging of the gut wall, that marks the anlage of the cecum and the boundary line between the large and small intestine. Succeeding changes in the intestine consist; (i) in its torsion and coiling, due to rapid elongation, and (2) in the differentiation of its several regions. As the gut elongates in 9 to 10 mm. embryos, the intestinal loop rotates. As a result, the originally caudal limb lies at the left and cranial to its cephalic limb (Fig. 95) of the small intestine soon lengthens so rapidly that the coelom can no longer accommodate it, and, at seven weeks, it protrudes into the umbilical cord and forms loops there (Fig. 96). This constitutes a normal umbilical hernia. Six primary loops occur and these may be recognized in the arrangement of the adult intestine. In embryos of ten weeks, spatial readjustments have allowed the intestine to return from the umbilical cord into the abdominal cavity; the coelom of the cord is obliterated soon after.


Fig. 95. - Median sagittal section of a 9 mm. human embryo, showing the digestive canal (Mall-Prentiss). X 9.



Vacuoles appear in the duodenal wall of embryos six to nine weeks old and epithelial septa completely block its lumen. The remainder of the small intestine becomes vacuolated but not occluded. Villi develop as rounded elevations of the epithelium at eight weeks. They begin to form at the cephalic end of the jejunum, and, at four months are found throughout the small intestine. Intestinal glands appear as ingrowths of the epithelium about the bases of the villi. They develop first in the duodenum at 14 weeks. The duodenal glands (of Brunner) are said to appear during the fourth month. In embryos of six weeks the circular muscle layer of the intestine first forms, but the longitudinal layer is not distinct until the end of the third month.


Fig. 96. - Median sagittal section of a 17 mm. human embryo, showing the digestive canal (Mall-Prentiss). X 5.


The large intestine, as seen in 9 mm. embryos (Fig 95), forms a tube extending from the cecum to the cloaca. It does not lengthen so rapidly as the small intestine, and, when the intestine is withdrawn from the umbilical cord, its cranial, or cecal end lies on the right side and dorsal to the small intestine (Fig. 97). It extends across to the left side as the transverse colon, then, bending abruptly caudad as the descending colon, returns by its sigmoid segment to the median plane and continues into the rectum. In fetuses from three to six months old, the lengthening of the colon causes the cecum and cephalic end of the colon to descend toward the pelvis (Fig. 97). The ascending colon is thus established in the position which it occupies in the adult. The distal end of the cecal anlage continues to elongate, but early lags in transverse development; as a result, the vermiform process is distinct from the cecum at the end of the third month. These structures make a sharp U-shaped bend with the colon at ten weeks, and this flexure gives rise to the colic valve.


Fig. 97. - Later changes in the intestine and dorsal mesentery of the human fetus (Tourneux in Heisler). i. Stomach; 2, duodenum; 3, small intestine; 4, colon, 5, yolk stalk; 6, cecum; 7, greater omentum; 8, mesoduodenum; 9, mesentery, 10, mesocolon. The arrow points to the orifice of the omental bursa. The ventral mesentery is not shown.


Fig. 98. - Development of the cecum and vermiform process (adapted from Kollman and Paterson). A, Two months; B, three months; C, early infancy; D, five years.


The Rectum. - The terminal portion of the intestine is derived by the horizontal division of the cloaca; Figs. 95 and 96, and 140 to 142 illustrate the process which is described in full on p. 145. When the anal membrane ruptures at the ninth week, the ectodermal proctodeum is added to the entodermal rectum.


The circular muscle layer of the large intestine appears first at two months, the longitudinal layer at three months. Between the third and seventh months villi are present.


Glandular secretions and desquamated entodermal cells, together with swallowed amniotic fluid, containing lanugo hairs and vernix caseosa, collect in the fetal intestine. This mass, yellow to brown in color, is known as meconium. At birth the intestine and its contents are perfectly sterile, but a bacterial flora is promptly acquired.


Anomalies. - The intestine may show atresia. This occurs most often in the duodenum as a retention of the embryonic occlusion. When the anal membrane fails to rupture, an imperforate anus results. If the rectum does not separate completely from the cloaca, a common urogenital and rectal cavity remains. Rarely there is nonrotation of the intestine and the colon lies on the left side. Two per cent of all adults show a persistence of the proximal end of the yolk stalk to form a pouch, Meckel - s diverticulum of the ileum (p. 52). Congenital umbilical hernia is due either to the continuance of the normally transitory embryonic condition or to a secondary protrusion of the viscera. Other hernias are explained on pp. 134 and 163.



Fig. 99. - Model of the liver anlage of a 4 mm. human embryo (Bremer). X 160. In., Intestine; Pa., pancreas; V., veins in contact with liver trabeculse.


In embryos of 2.5 mm., the liver anlage is present as a median ventral outgrowth from the entoderm of the fore-gut, just cranial to the yolk stalk (Fig. 71). Its thick walls enclose a cavity which is continuous with that of the gut. This hepatic diverticitluni becomes embedded at once in a mass of splanchnic mesoderm, the septum transversum (Fig. 91). Cranially, the septum will contribute later to the formation of the diaphragm; caudally, in the region of the liver anlage, it becomes Glisson - s capsule and the ventral mesentery (Figs, no and in). Thus, from the first, the liver is in close relation to the septum transversum, and later when the septum becomes the diaphragm, the liver remains attached to it (Fig. 113).


In embryos 4 to 5 mm. long, solid cords of cells proliferate from the ventral and cranial portion of the hepatic diverticulum (Fig. 91). These cords anastomose and form a crescentic mass with wings extending u]iward on either side of the gut (Fig. 93). This mass, a network of solid trabeula?, is the glandular portion of the liver, whereas the primitive, hollow diverticulum differentiates later into the gall bladder and the large biliary ducts. Referring to Fig. 183, it will be seen that the early liver anlage lies between the vitelline veins and is in close proximity to them laterally. The veins send anastomosing branches into the ventral mesentery. The trabeculce of the expanding liver grow between and about these venous plexuses, and the plexuses in turn make their way .



Fig. 100. - The trabeculae and sinusoids of the liver in section (after Minot). X 300. Tr., Trabeculae of liver cells; Si., sinusoids.


Between and around the liver cords (Fig. 99). The vitelline veins, on their way to the heart, are thus surrounded by the liver and largely subdivide into a network of vessels, termed sinusoids. The endothelium of the sinusoids is closely applied to the cords of liver cells, which, in the early stages, contain no bile capillaries (Fig. 100).

The glandular portion of the liver grows rapidly, and, in embryos of 7 to 8 mm., is connected with the primitive hepatic diverticulum by a single cord of cells only, the hepatic duct (Fig. loi A). That portion of the hepatic diverticulum distal to the hepatic duct is now differentiated into the terminal, solid gall bladder and its cystic duct; the proximal portion forms the ductus choledochus. In embryos of 10 mm. (Fig. loi B), the gall bladder and ducts have become longer and more slender and the hepatic duct receives a right and left branch from the corresponding lobes of the liver. The gall bladder is without a lumen up to the 15 mm stage, but later its cavity appears, surrounded by a wall of high, columnar epithelium.


The glandular portion of the liver develops fast and is largest relative to the size of the body at nine weeks. In certain regions the liver tissue undergoes degeneration, and especially is this true in the peripheral portion of the left lobe. In general, the external lobes of the liver are moulded under the influence of the fetal vitelline and umbilical trunks. The development of the ligaments of the liver is described on p. 126.



Fig. 101. - Reconstructions of the hepatic diverticulum and pancreatic anlages in human embryos. A, 7.5 mm. (Thyng). X 50; B, 10 mm. (Prentiss). X 33.


Fig. 102. - Diagrams illustrating the formation of liver lobules (Mall), a, Hepatic side; d, portal side; b and c, successive stages of the hepatic vein; e and f, successive stages of the portal vein.


During the development of the liver the endothelial cells of the sinusoids become stellate in outline, and thus form an incomplete layer. From the second month of fetal life to some time after birth, blood cells are actively differentiating between the hepatic cells and the endothelium of the sinusoids. At eight weeks hollow interlobular ducts appear spreading inward from the hepatic duct along the larger branches of the portal vein. In fetuses of ten weeks bile capillaries with cuticular borders are present, most numerous near the interlobular ducts with which some of them connect. At birth, or shortly after, the number of liver cells surrounding a bile capillary is reduced to two, three, or four. Secretion of the bile commences at about the end of the third fetal month.


The lobules, or vascular units of the liver, are formed, according to Mall, by the peculiar and regular manner in which the veins of the liver branch. The primary branches of the portal vein extend along the periphery of each primitive lobule, parallel to similar branches of the hepatic veins that drain the blood from the center of the lobule (Fig. 102). As development proceeds, each primary branch becomes a stem, giving off on either side secondary branches which bear the same relation to each other and to new lobules as did the primary branches to the first lobule. This process is repeated during fetal and early postnatal life until thousands of liver lobules are developed until the 20 mm. stage, the portal vein alone supplies the liver. The hepatic artery, from the cadiac axis, comes into relation first with the hepatic duct and gall bladder. Later, it grows into the connective tissue about the larger bile ducts and the branches of the portal vein, and also supplies the capsule of the liver.


Anomalies. - A common anomaly of the liver consists in its subdivision into multiple lobes. Absence or duplication of the gall bladder and of the ducts may occur. In some animals (horse; elephant) the gall bladder is absent normally.


THE PANCREAS


Two pancreatic anlages are developed almost simultaneously in embryos of 3 to 4 mm. The dorsal pancreas arises as a hollow outpocketing of the dorsal duodenal wall, just cranial to the hepatic diverticulum (Figs. 93 and 94). At 7.5 mm., it is separated from the duodenum by a slight constriction and extends into the dorsal mesentery (Fig. 10 1 A). The ventral pancreas develops in the inferior angle between the hepatic diverticulum and the gut, and its wall is at first continuous with both. With the elongation of the ductus choledochus, its origin is transferred to this portion of the diverticulum.


Fig. 103. - Stages in the development of the human pancreas (Kollman). 4 , 8 mm. ; B, 20 mm.



Of the two pancreatic anlages, the dorsal grows more rapidly, and, in 10 mm. embryos, forms an elongated structure with a central duct and irregular nodules upon its surface (Fig. loi B). The ventral pancreas is smaller and develops a short, slender duct that opens into the ductus choledochus. When the stomach and duodenum rotate, the pancreatic ducts shift their positions as well. At the same time, growth and bending of the bile duct to the right bring the ventral pancreas into close proximity with the dorsal pancreas (Figs. 101 and 103).


In embryos of 20 mm., the tubules of the dorsal and ventral pancreatic anlages interlock (Fig. 103 B). Eventually, anastomosis takes place between the two ducts, and the duct of the ventral pancreas, plus the distal segment of the dorsal duct, persists as the functional pancreatic duct (of Wirsung) of the adult. The proximal portion of the dorsal pancreatic duct forms the accessory duct (of Santorini), which remains pervious, but becomes a tributary of the chief pancreatic duct. The ventral pancreas forms part of the head and uncinate process of the adult gland. The dorsal pancreas participates in forming the head and uncinate process, and comprises the whole of the body and tail.


In 10 mm. embryos the portal vein separates the two pancreatic anlages, and later they partially surround the vein. The alveoli of the gland are derived from the ducts as darkly staining cellular buds in fetuses of ten weeks. The islands, characteristic of the pancreas, also bud from the ducts (and alevoli, Mironescu, 1910) and appear first in the tail a week later. Owing to the shift in the position of the stomach and duodenum during development, the pancreas takes up a transverse position.


Anomalies. - The ventral pancreas may arise directly from the intestinal wall, and paired ventral anlages also occur. Accessory pancreases are not uncommon. Both the dorsal and ventral ducts persist in the horse and dog; in the sheep and man, the ventral duct normally becomes of chief importance; in the pig and ox, the dorsal duct.


++++++++++++++++++++++++++++++++++++++++++++.

CHAPTER VI THE RESPIRATORY SYSTEM .


The development of the nose and pharynx are described elsewhere. Accordingly, the present account will deal exclusively with the origin of the other respiratory organs. In embryos of 23 segments, the anlage of this apparatus appears as a laryngo-tracheal groove in the floor of the entodermal tube, just caudal to the pharyngeal pouches. This groove produces an external ridge on the ventral wall of the tube which promptly becomes larger and rounded at its caudal end (Fig. 104). The groove and .


Fig. 104. - Stages in the early development of the trachea and lungs of human embryos (adapted by Prentiss). X about 50. A, 2.5 mm.; B, 4 mm.; C, stage B in side view; D, 5 mm. ; E, 7 mm.

The ridge are the anlages of the larynx and trachea. The rounded end of the ridge is the unpaired anlage of the lungs; in embryos of 4 to 5 mm. it becomes bilobed.


Externally, two lateral longitudinal grooves mark off the dorsal esophagus from the ventral respiratory anlages. A fusion of the lateral furrows, progressing cephalad, constricts first the lung anlages and then the trachea from the esophagus. At the same time the laryngeal portion of the groove and ridge advances cranially until it lies between the fourth branchial arches (Fig. 87). At 5 mm., the respiratory apparatus consists of the laryngeal groove and ridge, the tubular trachea, and the two lung buds (Fig. 104 D).


The Larynx. - In embryos of 5 to 6 mm., the oral end of the laryngeal groove is bounded on either side by two rounded prominences, the arytenoid swellings, which are continuous orally with a transverse ridge to form the furcula of His (Fig. 85). The transverse ridge becomes the epiglottis, derived from the third and fourth branchial arches (p. g6). In embryos of 15 mm., the arytenoid swellings are bent near the middle; their caudal portions lie parallel, while their cephalic segments diverge nearly at right angles (Fig. 105). The glottis, opening into the larynx, thus becomes T-shaped and ends blindly, as the laryngeal epithelium has fused. In fetuses of ten weeks this fusion is dissolved, the arytenoid swellings are withdrawn from contact with the epiglottis, and the entrance to the larynx becomes oval in form (Fig. 106). At eight weeks the ventndes of the larynx appear, and, during the tenth week, their margins indicate the position of the vocal cords. The elastic and muscle fibers of the cords are developed by the fifth month.



Fig. 105. - The larynx of a 16 mm. human embryo (Kallius). X 15.


At the end of the sixth week, the cartilaginous skeleton of the larynx is indicated by surrounding condensations of mesenchyme, derived from the fourth and fifth pairs of branchial arches (p. 221). The cartilage of the epiglottis appears relatively late. The thyroid cartilage is formed from the fusion of two lateral plates, each of which has two centers of chondrification. The anlages of the cricoid and arytenoid cartilages are originally continuous; later, separate cartilage centers develop for the arytenoids. The cricoid is at first incomplete dorsad, but eventually forms a complete ring; it therefore may be regarded as a modified tracheal ring. The corniculatc cartilages represent separated portions of the arytenoids. The cuneiform cartilages are derived from the cartilage of the epiglottis. The laryngeal muscles originate in the fourth and fifth branchial arches and are consequently innervated by the vagus nerve which supplies those arches.


The Trachea. - This tube gradually elongates during development, and its columnar epithelium becomes ciliated. Muscle fibers and the anlages of the cartilaginous rings appear in the condensed mesenchyme at the end of the seventh week. The glands develop as ingrowths of the epithelium during the last five months of fetal life.


The Lungs. - Soon after the lung anlages, or stem buds, are formed (in 5 mm. embryos), the right bronchial bud becomes larger and is directed .



Fig. 107. - Ventral and dorsal views of the lungs from a human embryo of about 9 mm. (after Merkel). Ap., Apical bronchus; Di, D2, etc., dorsal, V i. V2, ventral bronchi; Jc., infracardiac bronchus.


Straighter caudad (Fig. 104). At 7 mm. the stem bronchi give rise to two bronchial buds on the right side, to one on the left. The smaller bronchial bud on the right side is the apical {eparterial) hud. The right and left chief buds, known as ventral bronchi, soon bifurcate. There are thus formed three bronchial rami on the right side and two on the left; these correspond to the primitive lobes of the lungs (Figs. 88 and 107). On the left side, an apical bud is interpreted as being derived from the first ventral bronchus (Fig. 107). It remains small so that there is no separate lobe corresponding to the upper lobe of the right lung. The absence of this upper left lobe may be an adaptation to permit the normal caudal regression of the aortic arch (p. 190).


The bronchial anlages continue to branch in srich a way that the stem bud is retained as the main bronchial stem (Fig. 107). That is, the branching is monopodial, not dichotomous, lateral buds being given off from the stem bud proximal to its growing tip. Only in the later stages of development has dichotomous branching of the bronchi and the formation of two equal buds been described. Such buds, formed dichotomously, do not remain of equal size (Flint). The inclination of the heart to the left suppresses one of the larger ventral bronchial rami on that side, but at the same time it affords opportunity for an excessive development of the corresponding right ramus which then projects into the space between the heart and diaphragm as the infrasardiac bronchus (Fig. 107, Jc).



Fig. 108. - Transverse section through the lungs and pleural cavities of a 10 mm human embryo (Prentiss). X 23.


The entodermal anlages of the lungs and trachea are developed in a median mass of mesenchyme, dorsal and cranial to the peritoneal cavity. This tissue forms a broad mesentery, termed the mediastinum (Fig. 108). The right and left stem buds of the lungs grow out laterad, carrying with them folds of the mesoderm. The branching of the bronchial buds takes place within this tissue which is covered by the mesothelial lining of the future pleural cavity. The terminal branches of the bronchi are lined with entodermal cells; these flatten out and form the respiratory epithelium of the adult lungs. The surrounding mesenchyme differentiates into the muscle, connective tissue, and cartilage plates of the lung, tracheal, and bronchial walls. Into it grow blood vessels and nerve fibers. When the pleural cavities are separated from the pericardial and ])eritoneal cavities, the mesothelium covering the lungs, with the connective tissue underl3ung it, becomes the visceral pleura. The corresponding layers lining the thoracic wall form the parietal pleura. These layers are derived respectively from the visceral (splanchnic) and parietal (somatic) mesoderm of the embryo.


In 11 mm. embryos, the two pulmonary arteries, from the sixth pair of aortic arches, course first lateral then dorsal to the stem bronchi (Fig. 109). d he right pulmonary artery passes ventral to the apical (epar terial) bronchus of the right lung. The single pulmonary vein receives two branches from each lung: a larger vein from each lower lobe, a smaller vein from each upper lobe, including the middle lobe of the right side. These four pulmonary branches course ventrad and drain into the pulmonary trunk. When this common stem is taken up into the wall of the left atrium, the four pulmonary veins open directly in to the latter.


According to Kolliker, the air cells, or alveoli, of the lungs begin to form in the sixth month and their developnent is completed during pregnancy. Elastic tissue appears during the fourth month in the largest bronchi. The abundant connective tissue found between the bronchial branches in early fetal life becomes reduced in its relative amount as the alveoli of the lungs are developed.


Until birth the lungs are relatively small, compact, and possess sharp margins. They lie in the dorsal portion of the pleural cavities. After birth the lungs normally fill with air, expanding and completely filling the pleural cavities. Their margins are then rounded and the compact, fetal lung tissue, which resembles that of a gland in strrrcture, becomes light and spongy, owing to the enormous increase in the size of the alveoli and blood vessels. Because of the greater amount of blood admitted to the lungs after birth, their weight is suddenly increased.


Anomalies. - Variations occur in the size and number of lobes of the lungs; rarely there is a third lobe on the left side. The most common anomaly involving both esophagus and trachea is described on p. 104.


A striking malformation of the viscera in general is situs visccrum inversus, in which the various organs are transposed in position, right for left and left for right, as in a mirror image. This reversal may effect all the internal organs, or an independent transposition of the thoracic or abdominal viscera alone may occur. The early influence of the larger left great venous trunks is thought to be chiefly responsible for the usual positions and asymmetrical relations of the viscera.


Fig. 109. - Ventral view of the lungs of a 10.5 mm. embryo, showing the pulmonary arteries and veins (His in McMurrich). X 27. Ep., Apical bronchus; I, u, primary bronchi.


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CHAPTER Vu THE MESENTERIES AND COELOM


I. THE MESENTERIES


The Primitive Mesentery. - -The gut arises when the entoderm is folded into a tube (Fig. 165). At the same time, the lateral expanse of superposed splanchnic mesoderm swings inward from each side toward the midplane and forms a double-layered sheet, extending from the roof of the coelom to the midventral body wall and containing the gut between its layers (Figs, no and in). This membrane is the primitive mesentery. The covering layers of the gut (and other viscera), mesenteries, and body wall are continuous with each other and consist of a mesothelium, overlying connective tissue (Fig. ui). The parietal lining is derived from the somatic layer of mesoderm and the visceral covering from the splanchnic layer (Fig. 165).


Fig. 110. - Diagram showing the primitive mesenteries of an early human embryo in median sagittal section (Prentiss). The broken lines (A, B, and C) indicate the level of sections A , B, and C, in Fig. 111.




Fig. 111. - Diagrammatic transverse sections of an early human embryo (Prentiss). A, Through the heart and pericardial cavities; B, through the fore-gut and liver; C, through the intestine and peritoneal cavity. (Compare guide lines A, B, C, Fig. uo.) .


Differentiation of the Dorsal Mesentery. - At first, the gut is broadly attached dorsad and its roof lies directly beneath the notochord and descending aortee (Fig. 165). Presently this region of attachment becomes relatively narrow, and the gut is then suspended throughout most its length by a definite dorsal mesentery which extends like a curtain in the midplane. The esophagus lies in the mediastinum and has no typical mesentery in the adult (Fig. 124). On the contrary, that portion of the digestive canal which passes through the peritoneal cavity is contained in an originally continuous dorsal mesentery. Later, distinctive names are given to its several regions (Fig. no): thus, there is the dorsal mesogastrium (or greater omentum), of the stomach, the mesoduodenum, the mesentery proper of the small intestine, the mesocolon, and the mesorecinm.



Fig. 112. - Diagrammatic model cf an 8 mm. human embryo, showing the primitive omental bursa (Prentiss). The model is sectioned transversely, caudal to the liver, so the observer looks cephalad at the caudal surfaces of the liver and sectioned body.


The Omental Bursa. - The history of the mesogastrium is chiefly concerned with the development of a huge sacculation known as the omental bursa, or lesser peritoneal sac. According to Broman, its first indication in a 3 mm. embryo is a peritoneal pocket which extends cranially into the dorsal mesentery, to the right of the esophagus. A similar pocket, present on the left side, has disappeared in 4 mm. embryos. Lateral to the opening of the primitive bursa, a lip-like fold of the mesentery is continued caudally along the dorsal body wall into the mesonephric fold as the caval mesentery, in which the inferior vena cava develops later (Fig. 1 12). Furthermore, it will be remembered that the liver grows out into the ventral mesentery from the fore-gut, and, expanding laterally and ventrally, takes the form of a cresent. Its right lobe comes into relation with the caval mesentery, and, growing rapidly caudad, forms with this fold a partition between the lesser sac and the peritoneal cavity. Thus, the cavity of the omental bursa is extended caudally from a point opposite the bifurcation of the lungs to the level of the pyloric end of the stomach. In 5 to 10 mm. embryos, it is crescent-shaped in cross section (cf. Fig. Ill) and is bounded mesially by the greater omentum (dorsal mesentery) and the right wall of the stomach, laterally by the liver and caval mesentery, and ventrally by the lesser omentum (ventral mesentery) (Fig. 1 14). It communicates to the right with the peritoneal cavity through an opening between the liver ventrally and the caval mesentery dorsally (Figs. 114 and 116). This aperture is the epiploic foramen (of Winslow). When the dorsal wall of the stomach rotates to the left, the greater omentum is carried with it to the left of its dorsal attachment. The omental tissue grows actively to this side and caudally, and gives the omentum an appearance of being folded on itself between the stomach and the dorsal body wall (Fig. 113). The cavity of the omental bursa is carried out between the folds of the greater omentum as the inferior recess (Figs. 97 and 116).


From the cranial end of the sac there is constricted off a small closed cavity which is frequently persistent in the adult. This is the infra-cardiac bursa and may be regarded as a third pleural cavity. It lies at the right of the esophagus in the mediastinum when the stomach changes its position and form so that its midventral line becomes the lesser curvature and lies to the right, the position of the lesser omentum is also shifted. From its primitive location in a median sagittal plane, with its free edge directed caudally, the lesser omentum is rotated through 90° until it lies in a coronal plane with its free margin facing to the right. The epiploic foramen then forms a slitlike opening leading from the peritoneal cavity into the vestibule of the omental bursa (Fig. 114). The foramen is bounded ventrally by the edge of the lesser omentum, dorsally by the inferior vena cava, cranially by the caudate process of the liver, and caudally by the wall of the duodenum.


Fig. 113. - Diagrammatic model of a 14 mm. human embryo (adapted by Prentiss). The figure shows the caudal surface of a section through the stomach and spleen, a ventral view of the stomach, the liver having been cut away to leave the sectioned edges of the omental bursa and caval mesentery, and the caudal surface of the septum transversum and pleuro-peritoneal membrane. Upon the surface of the septum is indicated the attachment of the liver


During fetal life the greater omentum grows rapidly to the left and caudad, in the form of a sac, flattened dorso-ventrally. It overlies the intestines ventrally and contains the inferior recess of the omental bursa (Fig. 1 1 5). In the fourth month, the dorsal wall of the sac usually fuses with the transverse colon and mesocolon where it overlies them (Fig 115 B). The transverse mesocolon of the adult is conseciuently a double structure and the omental connection between stomach and colon becomes the gastro-coUc ligament. Caudal to this attachment, the walls of the omental bursa commonly unite and obliterate its cavity. The inferior recess of the omental bursa thus may be limited in the adult chiefly to a space between the stomach and the dorsal fold of the great omentum, which latter is largely fused to the peritoneum of the dorsal body wall. The s[)leen develops in the cranial portion of the great omentum; that stretch of the omentum extending between the stomach and spleen is known as the gastro-splenic ligament (Fig. 113), while its continuation beyond the spleen is the spleno-renal ligament.



Fig. 114. - Transverse section through a 10 mm. human embryo at the level of the stomach and epiploic foramen (Prentiss). X 33.


Fig. 115. - Diagrams showing the developmental relations of the greater omentum (Hertwig). A, Illustrates the beginning of the greater omentum and its independence of the transverse mesocolon: in B the two come into contact; in C they have fused. A, Stomach; B, transverse colon; C, small intestine; D, duodenum; E, pancreas; F, greater omentum; G, greater sac; H, omental bursa.


Other Changes in the Dorsal Mesentery. - As long as the gut remains a straight tube, the dorsal mesentery is a simple sheet whose two attached edges are equal in length. But when the intestine starts to elongate faster than the body wall, and forms first a loop and then coils, the intestinal attachment of the mesentery grows correspondingly and is carried out into the umbilical cord between the intestinal limbs. Even before this herniation of the intestine occurs, its limbs are so shifted that the cecal end of the large intestine comes to lie cranially and to the left, and the small intestine caudally and to the right; in this position the future duodenum and colon cross in close proximity to each other (Fig. 95). On the return of the intestinal loop into the abdomen, the cecal end of the colon is carried over to the right, and the transverse colon crosses the duodenum ventrally and cranially (Fig. 116 A). The primary loops of the small intestine lie caudal and to the left of the ascending colon. There has thus been a torsion of the mesentery about the origin of the superior mesenteric artery as an axis, which is accentuated as the limb of the ascending colon elongates toward the pelvis (Fig. 116 B). From this focal point, the mesentery of the small intestine and colon spreads out like a fan or funnel.



Fig. 116. - Diagrams showing the later history of the dorsal mesentery in ventral view (Tourneux-Prentiss). *, Cut edge of greater omentum; a, h, area of ascending and descending mesocolon fused to dorsal body wall. The arrow emerges from the omental bursa.



Previous to the middle of the fourth month, the gut is freely movable within the scope of its restraining mesentery, but soon secondary fusions occur which attach certain segments. The ascending and descending colon are applied against the body wall on the right and left side respectively. The flat surfaces of their mesenteries fuse with the adjacent dorsal peritoneum, and these two limbs of the colon become permanently anchored (Fig. 1 16). vSince the transverse colon passes ventral to the duodenum (Fig. 1 16), its mesentery remains distinct; but in the region of crossing, the base of the mesocolon fuses with the surface of the duodenum and pancreas. In accordance with its final position, this mesentery is now known as the transverse mesocolon. The line of attachment of the mesocolon presses the duodenum firmly against the dorsal body wall and obliterates its mesentery, thereby fixing this portion of the small intestine. The pancreas, which primarily is an outgrowth of the duodenum into the mesoduodenum, necessarily assumes also a retroperitoneal position behind the root of the transverse mesocolon. The mutual union of the lamellae of the greater omentum and its fusion to the transverse colon and the dorsal body wall have been mentioned. The mesentery proper of the small intestine is thrown into numerous folds, corresponding to the loops of the intestine, but normally does not exhibit secondary attachments; the sigmoid mesocolon likewise remains free.


Differentiation of the Ventral Mesentery. - The same splanchnic mesodermal layers that invest the entoderm and form the dorsal mesentery, also combine beneath the gut as the ventral mesentery (Figs, no and uI). The ventral mesentery is associated intimately with the development of two important organs. One is the heart, which becomes a single tube by the union of paired anlages lying one in each lateral fold of splanchnic mesoderm (Fig. 165). Hence the heart is supported by the ventral mesentery both above and below (Figs, no and in A). The other organ, the liver, grows downward into the ventral mesogastrium, splitting apart its component lamellae and then having similar mesenterial relations as the primitive heart (Figs, no and in B). Caudal to the yolk sac the ventral mesentery does not persist, even in young embryos (Figs, no and in C).


Most cephalad, the heart is suspended in the ventral mesentery which is there designated the dorsal and ventral mesocardium (Figs, -no and uI * 4 ). The latter is transitory and the dorsal mesocardium also disapjiears somewhat later, leaving the heart unsupported in the pericardial cavity (Fig. i66).


Ligaments of the Liver. - From the first, the liver is enclosed by the lamelte of the ventral mesogastrium, which, as the liver increases in size, give rise to its capsule and ligaments (Figs, no and in B). Wherever the liver is unattached, the enveloping mesodermal layers form the capsule (of Glisson), a fibrous layer covered by mesothelium, continuous with that of the jjeritoneum (Fig. in B). Along its mid-dorsal and midventral line, the liver remains connected to the ventral mesentery. That portion of the mesentery between the liver, stomach, and duodenum is the lesser omentum (Fig. 113). This in the adult is differentiated into the hepato-gastric and he pato-duodcnal ligaments. The mesogastrial attachment of the liver to the ventral body wall extends caudally from diaphragm to umbilicus and constitutes the falciform ligament.


In its early development, the liver abuts upon the primitive diaphragm, and, in 4 to 5 mm. embryos, is attached to it along its cephalic and ventral surfaces. Soon, dorsal prolongations of the lateral liver lobes, the coronary appendages, come into relation with the diaphragm dorsally and laterally (Fig. 124). The attachment of the liver to the septum transversum now has the form of a crescent, the dorsal horns of which are the coronary appendages (Fig. 113). This union becomes the coronary ligament of the adult liver. The dorso-ventral extent of the coronary ligament is reduced during development, and, at five months, its lateral extensions upon the diaphragm give rise to the triangular ligaments of each side.


The right lobe of the liver, comes into relation along its dorsal surface with the caval mesentery of 9 mm. embryos (Figs. 112 and 113). This attachment extends the coronary ligament caudally on the right side and makes possible the connection between the veins of the liver and mesonephros which contributes to the formation of the inferior vena cava. The portion of the liver included between the caval mesentery and the lesser omentum is the caudate lobe. The umbilical vein (later the ligamentum teres) courses in a deep groove along the ventral surface of the liver, and, with the portal vein and gall bladder, bounds the quadrate lobe.

In general, the several displacements and secondary fusions of the primitive mesentery cause its line of peritoneal attachment to depart throughout most of its extent from the original midsagittal position.


The special mesenterial supports of the urogenital organs will be described in the next chapter.


Anomalies. - The mesenteries may show malformations, due to the persistence of the simpler embryonic conditions, usually correlated with the defective development of the intestinal canal. In about 30 per cent of cases the ascending and descending mesocolon are more or less free, having failed to fuse with the dorsal peritoneum. The primary sheets of the greater omentum may also fail to unite, so that the inferior recess extends to the caudal end of the greater omentum, as is normal in many mammals.


II. THE COELOM .


Pericardial cavity Surface of fore-gut .


The Primitive Coelom. - The first occurrence of a coelom is in the extra-embryonic mesoderm (Fig. 40 C). vShortly after, numerous clefts appear in the embryonic mesoderm of each side and split it into somatic and splanchnic layers (cf. Fig. 325).

These clefts coalesce in the cardiac region and form two elongated pericardial cavities, lateral to the paired heart tubes (Fig 165 A, B). Similarly, right and left pleuro-peritoneal cavities are formed between the mesoderm layers caudal to the heart. The paired pericardial cavities extend toward the midplane cranial to the heart and presently communicate with each other (Figs. 117 and 165 C).


Laterally, they are not continuous with the extra-embryonic coelom, for in this region the head of the embryo has already separated from the underlying blastoderm .

The pericardial cavities, nevertheless, are prolonged caudally until they open into the pleuro-peritoneal cavities where these in turn communicate laterally with the extra-embryonic coelom. In an embryo of 2 mm., the coelom thus consists of a U-shaped pericardial cavity, the right and left limbs of which are continued caudally into the paired pleuro-peritoneal cavities; these extend out into the extraembryonic coelom (Fig. 117).


The primitive coelom lies in the horizontal plane (Fig. 117). Coincident with the caudal regression of the primitive diaphragm, the pericardial cavity is bent ventrad and enlarged (Fig. 118). The ventral mesocardium, attaching the heart to the ventral body wall, disappears, and the right and left limbs of the U-shaped cavity become confluent, ventral to the heart. The result is a single, large pericardial chamber, the long axis of which now lies in a dorso-ventral plane, nearly at right angles to the plane of the pleuro-peritoneal cavities, and connected with them dorsally by the right and left pleuro-pericardial canals. On account of the more rapid growth of the embryo, there is an apparent constriction at the yolk stalk, and, with the development of the umbilical cord, the peritoneal cavity is separated definitely from the extra-embryonic coelom (Fig. 45). Dorsally, the pleural and peritoneal cavities are permanently partitioned lengthwise by the dorsal mesentery.


Pleuro-peritoneal canal Entoderm of gut Peritoneal cavity Extra-embryonic coelom Wall of yolk sac

Fig. 117. - Diagrammatic model of the fore-gut and coelom in an early human embryo, viewed from above and behind (Robinson-Prentiss)

the cavities of the mesodermal segments are regarded as portions of the coelom, but in man they disappear early. The development of the vaginal sacs, which grow out from the inguinal region of the peritoneal cavity into the scrotum, will be described in Chapter VuI the division of the primitive coelom into separate cavities is accomplished by the development of three types of membrane that join on each side in a Y-shaped fashion (Figs. 122 and 123); (i) the unpaired septum transversum, which separates partially the pericardial and pleural cavities from the peritoneal cavity; (2) the paired pleuro-pericardial membranes, which complete the division between pericardial and pleural cavities; (3) the paired pleuro- peritoneal membranes, which complete the partition between each pleural cavity and the peritoneal cavity.


Fig. 118. - Reconstruction, cut at the left of the median sagittal plane of a 3 mm. human emhryo, showing the body cavities and septum transversum (Kollmann).


The Septum Transversum. - The vitelline veins, on their way to the heart, course in the splanchnic mesoderm lateral to the fore-gut (Fig. 183). In embryos of 2 to 3 mm., these large vessels bulge into the coelom until they meet and fuse with the somatic mesoderm (Fig. 381). Thus, there is formed caudal to the heart a transverse partition, filling the space between the sinus venosus of the heart, the gut, and the ventral body wall, and separating the pericardial and peritoneal cavities from each other ventral to the gut (Fig. i66). This mesodermal partition was termed by His the septum transversum. In Fig. u8 it comprises both a cranial portion (designated - septum transversum - that is the anlage of a large part of the diaphragm, and a caudal portion, the ventral mesentery, into which the liver is growing.


At first the septum transversum does not extend dorsal to the gut, but leaves on either side a pleura- peritoneal canal through which the pericardial and pleuro-peritoneal cavities communicate (Fig. 1 1 8). In embryos of 4 to 5 mm., the lungs develop in the median walls of these canals and bulge laterally into them (Fig. 120). Thus the canals become the pleural cavities, and will be so termed hereafter.


The septum transversum of 2 mm. embryos occupies a transverse position in the middle cervical region (Fig. 119, 2). It then migrates caudally, the ventral portion at first moving more rapidly so that its position becomes oblique. In 5 mm. embryos (Fig. 119, 5) the septum is opposite the fifth cervical segment, at which level it receives the phrenic nerve. During a second period of migration the dorsal attachment travels faster than the ventral portion, and as a result the septum rotates to a position nearly at right angles to its plane at 7 mm. The final location, opposite the first lumbar segments, is attained in an embryo of two months.


The Pleuro-pericardial and Pleuro-peritoneal Membranes. - The common cardinal veins (ducts of Cuvier), on their way to the heart, curve around the pleural cavities laterally in the somatic body wall (Fig. 118). In embryos of 7 mm., each vein, with the overlying mesoderm, forms a ridge that projects from the body wall mesially into the adjacent pleural canal. This ridge, the pulmonary ridge (of Mall), is the anlage of both the pleuro-pericardial and pleuro-peritoneal membrane (Figs. 118 and 120). Later, it broadens and thickens cranio-caudally (Fig. 121), forming a triangular structure whose apex is continuous with the septum transversum (Fig. 122). Its cranial side constitutes the pleuro-pericardial membrane, and, in g to 10 mm. embryos, reduces the opening between the pleural and pericardial cavities to a mere slit. Its caudal side becomes the pleuro-peritoneal membrane, which later completes the partition dorsally between the pleural and peritoneal cavities (Fig. 123).

.


Fig. 119. - Diagram showing the migration of the septum transversum (MallPrentiss). Numerals indicate the length of the embryo at each position of the septum. The letters and numbers at the right represent the occipital, cervical, thoracic and lumbar segments.


Fig. 120. - Reconstruction of a 7.5 mm. human embryo, cut across and viewed caudally to show the body cavities and pulmonary ridge (Kollman).


Fig. 121. - Reconstruction of a 7 mm. human embryo, showing from the left side the pleuro-pericardial membrane, the pleuro-peritoneal membrane and the septum transversum (Mall in Prentiss). X 20. The phrenic nerve courses in the pleuro-pericardial membrane. An arrow jiasses from pericardial to peritoneal cavity through the pleuro-pericardial canal.



Fig. 122. - Reconstruction of an 1 1 mm. human embryo, to show the structures of Fig. 121 at a later stage (Mall in Prentiss). X 14.

The two sets of membranes at first lie nearly in the sagittal plane, and a portion of each lung is caudal to the corresponding pleuro-peritoneal membrane (Fig. 121). Between the stages of 7 and u mm. the dorsal attachment of the septum transversum shifts caudad more rapidly than its ventral portion, and carries the pleuro-peritoneal membrane with it until the latter lies caudad to the lung (Figs, ug, 121 and 122). Each lung then occupies a spherical triangle between pleuro-pericardial and pleuro-peritoneal membranes (Fig 122). During this rotation the dorsal end of the pleuro-pericardial membrane lags behind, anchored by the phrenic nerve which courses through it, and so takes up a position in a coronal plane nearly at right angles to the septum transversum (Figs. 122 and 123). In 1 1 mm. embryos, the pleuro-pericar dial membranes have fused completely on each side with the median walls of the pleural cavities (Fig. 123).


The pleuro-peritoneal membranes are continuous dorsally and caudally with the mesonephric folds; ventrally and caudally, they fuse later with the dorsal pillars of the diaphragm, or coronary appendages of the liver (Figs. 113 and 124). Between the free margins of the membranes and the mesentery a temporary opening is left on each side, through which the pleural and peritoneal cavities communicate (Figs. 108, 113 and 122). Owing to the caudal migration of the septum transversum and the growth of the lungs and liver, the pleuro-peritoneal membrane, at first lying in a nearly sagittal plane (Figs. 120 and 12 1), is shifted to a horizontal position (Fig. 122), and gradually its free margin unites with the dorsal pillars of the diaphragm and with the dorsal mesentery. The opening between the pleural and peritoneal cavities is thus narrowed and finally closed in embryos of 19 to 20 mm.


Fig. 123. - Transverse section through a 10 mm. human embryo, showing the pleuro-pericardial and pleuro-peritoneal membranes (Prentiss). X 33.


The Pericardium and Diaphragm. - The lungs grow and expand, not only cranially and caudally but also laterally and ventrally (Fig. 125). Room is made for them by the obliteration of the very loose, spongy mesenchyme of the adjacent body wall (Fig. 124). As the lungs burrow laterally and ventrally into the body wall around the pericardial cavity, the pleuro-pericardial membranes enlarge at the expense of this tissue and more and more the heart comes to lie in a mesial position .


Fig. 124. - Transverse section through a 10 mm. human embryo, showing the fusion of the pleuro-peritoneal membranes with the coronary appendages (Prentiss). X 16.

Between the lungs, but separated from them by the pericardium (Fig. 125 B). The pleural cavities thus increase rapidly in size at the same time the liver grows enormously, and on either side a portion of the body wall is taken up into the septum transversum and pleuro-peritoneal membranes. The diaphragm, according to Broman, is thus derived from four sources (Fig. 126): (i) its ventral pericardial portion from the septum transversum; its lateral portions from (2) the pleuro-peritoneal membranes, plus (3) derivatives from the body wall; (4) lastly, a median dorsal portion is formed from the dorsal mesentery. In addition to these, the striated muscle of the diaphragm takes its origin from a pair of premuscle masses, which, in 9 mm. embryos, lie one on each side opposite the fifth cervical segment (Bardeen). This is the level at which the phrenic nerve enters the septum transversum (Fig. 124). The exact origin of these muscle anlages is in doubt, but they probably represent portions of the cervical myotomes of this region. The muscle masses migrate caudally with the septum transversum and develop chiefly in the dorsal portion of the diaphragm.


Fig, 125. - Diagrams showing the development of the lungs and the formation of the pericardium (Robinson-Prentiss). A, Coronal section; B, transverse section.


Fig. 126. - Diagram showing the contributions to the diaphragm (Broman). i. Septum transversum; 2, 3, dorsal mesentery; 4, 4, pleuro-peritoneal membranes; 5, 5, bodj' wall; A, aorta; Oe, esophagus; VC, inferior vena cava.


Anomalies. - The persistence of a dorsal opening in the diaphragm, more commonly on the left side, finds its explanation in the imperfect development of the pleuro-peritoneal membrane. Such a defect may lead to diaphragmatic hernia, the abdominal viscera projecting to a greater or less extent into the pleural cavity. Similarly, faulty development of the left pleuro-pericardial membrane sometimes causes the heart and left lung to occupy a common cavity. An intact diaphragm, locally deficient in muscle, may herniate,


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