Pronephros

Significant function of the pronephros is limited to the lower vertebrates, fish for example. In most mammals the pronephros is rudimentary and consists of seven or eight pairs of pronephric tubules that appear briefly at the level of somites seven to 14. In the intermediate mesoderm of this region, a duct, the pronephric duct, develops and grows caudally to the cloaca. In the sheep, pronephric tubules become quite well developed and connect to the pronephric duct.

Mesonephros

The mesonephros is fully operational in lower vertebrates like amphibians. In mammals, the mesonephros is a vestige of the nephrogenic cord, and its appearance is transitory. The mesonephros and its mesonephric duct are derived from intermediate mesoderm that extends from upper thoracic to upper lumbar segments. In domestic animals, 70–80 pairs of mesonephric tubules appear approximately between the levels of somites nine through 26. Each tubule is apposed to a blood vessel on one end, and connects into the posterior end of the pronephric duct on the other. The duct grows towards the cloaca and forms the mesonephric or Wolffian duct. The mesonephric tubules lengthen rapidly, form an S-shaped loop, and acquire a tuft of capillaries that later form the glomerulus at their medial extremity. The glomeruli are supplied by a rich vascular plexus, composed of numerous lateral branches of the dorsal aorta, within the mesonephros. Around each glomerulus, the tubulus forms a Bowman’s capsule. Together these structures constitute a renal corpuscle. Laterally, the tubules join the longitudinal collecting duct, the mesonephric duct.

The fully developed mesonephros is of considerable size in domestic animals, forming an ovoid organ on each side of the midline (Figs 15-2, 15-3). Due to its size, it is partly responsible for the physiological herniation of the growing intestinal loop (see Chapter 14). The size of the mesonephros correlates to some extent with the type of placenta and how well the placenta cleans the blood. Thus, it is largest in species with a six-layered placental barrier (epitheliochorial placenta; see Chapter 9) such as the pig and sheep, and smallest in carnivores with a four-layered barrier (endotheliochorial placenta). Soon after their formation, most of the mesonephric tubules start to degenerate. Degeneration of the cranial portion of the mesonephros occurs around the eighth and ninth week of gestation in the horse, and tenth week in cattle.

Fig. 15-2: Mesonephros in a pig embryo at Day 21 of development. 1: Mesonephros; 2: Liver.

Fig. 15-3: Higher magnification of the mesonephros in a pig embryo at Day 21 of development. 1: Mesonephros; 2: Mesonephric (Wolffian) duct; 3: Glomeruli of the mesonephros; 4: Mesonephric tubuli.

Metanephros

It is the third generation of urinary organs, the metanephros, that matures to form the permanent kidney (Figs 15-4, 15-5). In cattle, its development begins at the level of somites 26 through 28, when the embryo is about 6–7 mm in length. The metanephros is derived from two primordial structures: the ureteric bud, an outgrowth of the mesonephric duct, and the metanephric blastema, which is located in the sacral region and originates from the posterior end of the nephrogenic cord. In forming the metanephros, the ureteric bud grows anteriodorsally into the overlying posterior intermediate mesoderm where it interacts with this loosely organized mesenchyme, the metanephric blastema, located on the lateral aspect of the aorta. This epithelial-mesenchymal interaction leads to a dramatic transformation of the mesenchyme into an epithelial phenotype, which reciprocates by inducing the ureteric bud to undergo arborization and generation of nascent nephrons.

Fig. 15-4: Stages in the development of a metanephric tubule. A: As the terminal bud of the metanephric duct branches, the surrounding mesenchyme cells split into parts. A single condensation of mesenchymal cells goes through a defined series of stages to form a renal tubule.1: Ureteric bud with two ampullae; 2: cap of metanephric tissue; 3: Renal vesicle. B: The renal vesicle gives rise to small S-shaped tubules. Capillaries (6) grow into the pocket (5) at one end of the S and differentiate into glomeruli. 1: Ampulla; 1′: Collecting tubule; 4: Renal tubule. C: At the points where the collecting tubule (1′) splits, numerous nephrons consisting of corpuscula renales (7) and renal tubules (8) develop. D: The nephron forms proximal (9) and distal (10) convoluted tubules, which are connected by the Henle’s loop (11). E: Differentiated corpusculum renis. 12: Glomerulus; 13: Bowmans capsule.

Courtesy Sinowatz and Rüsse (2007).

Fig. 15-5: Development of a metanephrogenic excretory unit in a bovine embryo of 17 mm CRL. 1: Ureteric bud; 2: Caps of metanephric tissue.

Collecting system

The combination of elongation and branching (up to 14 or 15 dichotomous branching divisions) of the ureteric bud plays a central role in the development of the metanephros (Fig. 15-6). Outgrowth of the ureteric bud from the mesonephric duct is induced by the secretion of alial-derived neurotrophic factor (GDNF) by glial cells derived from the undifferentiated mesenchyme of the metanephrogenic blastema. GDNF secretion is controlled by WT-1, a transcription factor that makes the mesenchyme competent to respond to induction by the ureteric bud. The inductive signal GDNF is bound by c-Ret, a member of the tyrosine kinase receptor superfamily, which is located in the plasma membrane of the epithelial cells of the ureteric bud. In response to GDNF, the epithelial cells of the ureteric bud produce fibroblast growth factor 2 (FGF2), BMP1/BMP2, and leukaemia inhibitory factor (LIF), which stimulate the surrounding metanephric mesenchyme to form precursors of renal tubules.

Fig. 15-6: Nephron induction and patterning.

A: Glial-derived neurotrophic factor (GDNF) released from mesenchymal cells (blue) surrounding the ureter binds to the RET receptor at the tip of the ureter (red) and induces growth and branching. RET signalling activates WNT11, which is required in a positive-feedback loop to maintain expression of GDNF in the metanephric mesenchyme. Retinoic acid signalling (RA) from stromal cells (pink) is required to maintain RET expression in the ureteric bud. Sine oculis homeobox homologue 2 (SIX2) suppresses tubulogenesis in renal precursor cells (purple), which reside at the outer cortex of the developing kidney.

B: WNT9B released from stalk regions of the ureter induces canonical β-catenin signalling in the metanephric mesenchyme, which activates a molecular cascade involving fibroblast growth factor 8 (FGF8), the LIM homeobox protein LIM1 (also known as LHX1) and WNT4. WNT4 induces the mesenchyme-to-epithelial transition and the formation of the renal vesicle (brown).

C: LIM1 is required to induce the initial stages of patterning in the renal vesicle, by controlling the expression of the POU-domain transcription factor BRN1 and Delta-like protein 1 (DLL1) at the pole of the vesicle that lies in close proximity to the ureter. Expression of the Wilms tumour transcription factor (WT1) becomes restricted to the presumptive podocyte layer of the comma-shaped body, where it suppresses paired-box protein 2 (PAX2).

D: The comma-shaped body extends to form an S-shaped structure. Under the control of transcription factors, distal segments further extend and differentiate towards distal tubule segments (with a high concentration of BRN1) and intermediate tubule segments. NOTCH2 controls proximal tubule fate. Podocyte cells mature under the control of transcription factors such as WT1 and LIM homeobox transcription factor 1B (LMX1B), and release signals (vascular endothelial growth factor (VEGF)) that attract endothelial cells (red), which in turn produce factors (for example, platelet-derived growth factor (PDGF) that support the differentiation of mesangial cells.

E: A patterned nephron showing the vascular loop (red), podocytes (dark green), Bowman’s capsule (light green), proximal convoluted tubule (blue), intermediate segments with Henle’s loop (orange), distal convoluted tubule (yellow) and collecting duct (dark red).

Modified from Schedl (2007).

The formation of functional nephrons in the developing metanephros involves three cell lineages, all derived from the mesoderm: epithelial cells from the ureteric bud, mesenchymal cells of the metanephric blastema, and ingrowing endothelial cells. The first step of nephron formation is the condensation of mesenchymal blastema cells around terminal buds of the branching ureteric bud. As the mesenchymal cells condense, the expression of several proteins typically found in mesenchymal cells (like collagen I, collagen III, and fibronectin) is lost and replaced by epithelial-type proteins like collagen IV, syndecan-1, and laminin, which ultimately contribute to the basal membrane around the tubular cells.

The mesenchymal condensations of the metanephric blastema around the terminal buds of the branches develop into a renal tubule in stages. The aggregates of metanephric blastema cells organize into an epithelial cord that canalizes to form a tubule (Fig. 15-4). The primordium of the tubule first assumes a comma shape, with a central lumen at its distal end and a basal lamina assembled on its outer surface. These events mark the transformation of mesenchymal cells into an epithelium. Subsequently, a slit-like space develops outside the transforming podocyte precursors in the tubular primordium, and precursors of vascular endothelial cells migrate into this space. These vascular endothelial cells ultimately form the capillaries of the glomerulus, which are connected with branches of the lateral segmental arteries arising from the aorta. Between the cells of the glomerular endothelium and the neighbouring podocytes, a thick basal lamina is formed that later serves as an important component of the renal filtration barrier.

As the glomerular component of the nephron takes shape, the comma-shaped tubular primordium is transformed into an S-shaped structure. During this process the rest of the tubule primordium acquires the characteristics of epithelial cells. The cells now express E-cadherin, which seals the lateral border of the cells, and laminin is deposited at their basal surfaces. A characteristic pattern of gene expression can be observed along the length of the S-shaped tubules: near what will later be the glomerular end of the tubule, WT-1 becomes strongly expressed, whereas Pax2 expression declines. At the other end (the future distal convoluted tubule) expression of both Wnt-4 and E-Cadherin remain prominent. In the middle part of the S-shaped tubule (the future proximal convoluted tubule) K-cadherin expression remains high. Later, differentiation of the renal tubule progresses from the proximal to the distal convoluted tubule. The middle part of each tubule develops into an elongated, thin, hairpin-like loop that extends into the medulla of the kidney and is referred to as the tubulus attenuatus or the loop of Henle. During the differentiation, the tubular epithelial cells also acquire molecular features characteristic of mature kidney cells, including expression of brush border antigens or the Tamm-Horsfall protein. The mature nephrons each consist of a renal corpuscle located in the outer cortical portion of the kidney, and an elongated tubular loop that extends centrally and contributes to the medulla of the kidney.

Development of the kidney involves the formation of approximately 15 successive generations of nephrons in the peripheral cortical zone (Figs 15-7, 15-8, 15-9). The first renal corpuscles to form are located at the corticomedullary junction. Many of the early nephrons become apoptotic during later fetal stages. Collecting tubules elongate and new generations of nephrons are induced and form at progressively more superficial levels. Thus, the outermost nephrons are less mature than are those located deeper in the cortex. Depending on the species, nephrogenesis ceases at or shortly after birth; nephrogenesis continues during the first weeks post partum in the dog, and for the first three weeks in the pig. The number of nephrons formed differs between the species: about 200 000 nephrons form in the feline kidney, 300 000–500 000 in the dog, and 1.5–4 million in ruminants and pigs.

Fig: 15-7: Metanephros and regressing mesonephros of a bovine fetus with a CRL of 30 cm. 1: Metanephros; 2: Mesonephros.

Fig. 15-8: Metanephros (1) and adrenal gland (2) of a bovine fetus with a CRL of 12.7 cm.

Fig. 15-9: Development of the renal pelvis, calyces and collecting tubules of the metanephros. A: Splitting of the ureteric bud in the metanephrogenic blastema. B: Indifferent stage of the metanephros: C–F: Differentiation of the metanephros in carnivores (C), pig (D), bovine (E), and horse (F).

Courtesy Sinowatz and Rüsse (2007).

The variations in macroscopic appearance of the mature kidney result from differences in the branching of the ureteric bud and the arrangement of nephrons associated with these branches (Fig. 15-9). In cattle, the ureteric bud, from which the ureter is derived, forms two major branches (primary branches) that subdivide into 12 to 25 minor (secondary) branches. Consequently, the bovine kidney develops 12–25 separate lobes, each retaining its distinct pyramid-forming papillae. The bovine kidney is therefore often referred to as a multipyramidal kidney. The papillary ducts within each lobe drain into a calyx. The bovine kidney differs from that of the other domestic animals in having no renal pelvis.

In the pig, although the cortex is not lobated, the medulla is subdivided into renal pyramids forming papillae and so the porcine kidney is also multipyramidal. Each papilla consists of nephric loops and the collecting tubules and ducts that empty into terminal branches of a minor calyx. The dilated end of the porcine ureteric bud forms the renal pelvis. From the two major divisions of the renal pelvis (major calyces) up to ten funnel-shaped minor calyces originate. Despite it superficially smooth appearance, the multilobular structure of the porcine kidney reveals itself in both its multipyramidal appearance and the separate drainage of each lobe through minor calyces.

In the horse, small ruminants, and carnivores no calyces are formed and the papillary duct drains directly into a common pelvis. In the horse, the renal pelvis possesses two long, thin-walled processes (terminal recesses) in which the urine is collected. The terminal recesses are lined by the same epithelium as the collecting ducts and may be regarded as fusions of collecting ducts originating from the nephrons located near the poles of the kidney. The cortex undergoes a complete fusion resulting in a non-lobated, smooth surface of the kidney. Moreover, fusion of the apical regions of the medullary pyramids results in the formation of a ridge-like common papilla, the renal crest. All collecting ducts open into the pelvis on this ridge which runs on the roof of the pelvis. The deep lateral recesses of the canine pelvis do not collect urine, but segregate the medullary regions into wedge-shaped structures called renal pyramids

The metanephric kidney develops first in the pelvic region of the embryo. However, due to the extensive growth and elongation of the posterior portion of the fetus, in a relative sense the kidney ascends a short distance into the abdomen and in most species becomes situated ventral to the cranial lumbar vertebrae. The ureter elongates accordingly, commensurate with fetal growth.

Bladder and urethra

During development of the hindgut, the cloaca is subdivided by the urorectal septum into the rectum (dorsally) and the urogenital sinus (ventrally). The latter comprises an anterior pelvic region and a posterior phallic region (Fig. 15-10). Cranially, the urogenital sinus is connected to the allantoic cavity through the urachus which is continued in the allantoic stalk. After degeneration of the cloacal membrane the allantoic stalk opens caudally into the amniotic cavity through the urogenital orifice.

Fig. 15-10: Differentiation of the Wolffian and Müllerian ducts and dislocation of the urethra during the development of male and female genital organs.

A and B: Indifferent stage: 1: Mesonephros and genital ridge (stippled); 2: Wolffian duct; 3: Ureteric bud; 4: Müllerian duct; 5: Sinus urogenitalis (later urinary bladder) with primary urethra (5′). 6: Cloaca; 7: Rectum; 8: Septum urorectale.

C: Female genital organs: 1: Ovary; 2: Gardner’s duct (remainings of the mesonephric duct); 3: Metanephros with ureter (3′); 4: Uterus; 5: Urinary bladder with urethra (5′) and vestibulum (5″); 6: Perineum; 7: Rectum; 8: Septum urorectale; 9: Clitoris.

D: Male genital organs: 1: Testis; 2: Epididymis; 2′: Ductus deferens; 3: Metanephros with ureter (3′); 5: Urinary bladder with urethra (5′); 6: Perineum; 7: Rectum; 8: Septum urorectale; 9: Penis.

Courtesy Sinowatz and Rüsse (2007).

The bladder forms from the proximal portion of the urachus and the pelvic region of the urogenital sinus (Figs. 15-10, 15-11). The attenuated distal end of the urachus solidifies into a cord-like structure, which is suspended in a peritoneal fold that ultimately forms the median umbilical ligament, leading from the bladder to the umbilical region. As the bladder grows, its expanding wall incorporates the terminal portions of mesonephric ducts and the ureteric buds, and each duct system develops its own separate openings into the developing bladder. Initially, the mesonephric ducts open anterior to the ureteric buds, but gradually the positions of these orifices shift, so that the ends of the ureteric buds finally open into the bladder laterally and anterior to the mesonephric ducts. A triangular area in the dorsal wall of the neck of the bladder and the cranial urethra represents the region of mesonephric duct and ureteric bud incorporation. The base of this trigone is delineated anteriorly by the entrance of the forming ureters. The apex is located where the mesonephric ducts each enter to form the ductus deferens on either side of a small swelling referred to as the urethral crest. The trigone in the dorsal wall of the bladder is lined by epithelium of mesodermal origin whereas the rest of the bladder epithelium is derived from the endoderm. The non-epithelial components of the bladder wall (connective tissue and smooth muscle) are derived from the visceral mesoderm.

Fig. 15-11: Dorsal view of the bladder showing the relation of the ureters and the mesonephric ducts during development. A: Initially the ureters are formed by an outgrowth of the mesonephric duct, but with time they assume a separate entrance into the urinary bladder (B-D). 1: Mesonephric duct; 2: Ureteric bud; 3: Urinary bladder; 4: Trigone of the bladder (trigonum vesicae); 5: Urethra.

Courtesy Sinowatz and Rüsse (2007).

In the female, the urethra develops from the anterior portion of the pelvic urogenital sinus and the remainder of the sinus forms the vestibule. In the male, the caudal urogenital sinus gives rise to the penile urethra.

Sex determination

Chromosomal sex is established at fertilization, when a Y- or an X-chromosome-bearing spermatozoon fuses with the oocyte to determine the genetic sex of the zygote. The sex determining region of the Y gene (Sry), a member of the Sox family of transcription factors, is the testis-determining gene. It is located within a 35-kilodalton region on the short arm of the Y-chromosome. In the mouse, Sry encodes a 223 amino acid DNA-binding protein of the high mobility group (HMG) box class. It presumably regulates the expression of other genes, which then confer the cellular phenotype. Additional evidence that Sry is the Y-encoded testis-determining gene has come from experiments with transgenic mice: sex reversal from female to male was found after a small genomic fragment carrying the mouse Sry gene was introduced as a transgene into XX embryos. These results demonstrate not only that Sry is involved in testis determination, but that it is the only gene of the Y chromosome that is required for this process. Although the genetic sex of the embryo is fixed at fertilization, the gross sex-specific phenotype is not apparent until after 4 to 7 weeks of development, depending on the species. Subtle differences, however, are expressed much earlier as it has been demonstrated that the rate of development up to the blastocyst stage is faster in males than in females.

Primordial germ cells and indifferent stage of gonadal development

During the indifferent stage of gonadal development, primordial germ cells (PGCs) migrate from the yolk sac into the gonadal primordium (see Chapter 4). The PGCs are the source of germ cells in the adult gonad. PGCs can first be identified in the epiblast, where their formation, at least in mice, is dependent upon the expression of BMP4 by the extraembryonal ectoderm (see Chapter 20). The extraembryonic ectoderm is formed during development of the amnion in mice, and, because amniogenesis is basically different in the domestic animals and the mouse, it is uncertain whether a similar mechanism operates in the domestic species. PGCs can be identified histochemically by their high alkaline phosphatase activity and by their expression of pluripotency transcription factors such as Oct4. These cells pass through the early primitive streak and become located as a small cluster of cells in the extraembryonic mesoderm, near the base of the allantois. They then become incorporated into the endoderm of the posterior wall of the yolk sac, where they are apparently further dislocated from the embryonic disc. Subsequently, the PGCs shift to a site in the mesoderm along the yolk sac and allantois stalks. From there they apparently migrate in the wall of the hindgut and through the dorsal mesentery until they reach the newly formed genital ridge (Fig. 15-12).

Fig. 15-12: Cross section through a sheep embryo of 17 mm CRL. 1: Genital ridge; 2: Mesonephros; 3: Aorta; 4: Wolffian duct.

Studies in mutant mice have demonstrated that the passage of PGCs to the dorsal mesentery and into the genital ridges probably requires active locomotion. This, especially the initial stages of migration, is accomplished by active amoeboid movement of the cells in response to molecular clues form the extracellular matrix. In avian species, PGCs reach the genital ridge via the blood stream. PGCs divide during migration to the gonadal primordia in response to mitogenic factors such as LIF and Steel factor and many remain linked to one another through long cytoplasmic processes. They also express the transcription factor Oct4, which is involved in the maintenance of their pluripotent state (see Chapter 4) and is the same gene that maintains the undifferentiated state of blastomeres and the ICM in developing embryos (see Chapter 6). PGCs can be found in the genital ridge by Day 16 in the pig, Day 21 in dogs, Day 22 in sheep, Day 25 in cattle, and Day 28 in humans. Approximately 1000 to 2000 PGCs enter the genital ridge. A few days after colonizing the genital ridges, PGCs undergo mitotic arrest. In the testis primordium the PGCs do not enter meiosis until puberty whereas meiosis is initiated during fetal development in the ovary primordium.

The gonads develop from an elongated region of steroidogenic mesoderm along the ventromedial border of the mesonephros. As already described, the mesonephros is a primitive kidney developing from unsegmented, intermediate mesoderm. The early genital ridge consists of three major cell populations: local mesenchymal cells, cells derived from the coelomic epithelium, and cells originating from the regressing mesonephric tubules that invade the presumptive gonadal tissue. Recently, some of the molecular mechanisms of gonadal differentiation have been established. One of the earliest genes required for the formation of the gonads is WT-1 which is expressed throughout the intermediate mesoderm and also plays an important role in the development of kidneys. Lim-1 is another major gene involved in the early phase of gonadal development: in its absence no gonads form. Another gene, steroid factor 1, is expressed in the early indifferent gonad as well as in the developing adrenal medulla, which forms from cells in the cranial part of the steroidogenic mesoderm.

Although the sex of a mammalian embryo is determined genetically at the time of fertilization, the genital ridges remain morphological indifferent during the first weeks of gestation. When the PGCs arrive in the gonadal ridge, the resident mesenchymal cells and the coelomic epithelium proliferate and, consequently, the developing gonadal ridges project into the coelomic cavity (Figs. 15-12, 15-13). This ridge forms in embryos of approximately 9–10 mm CRL and grows quickly when the PGCs arrive. Cords of epithelial cells from the mesonephric tubules and regressing glomerular capsules penetrate the mesenchyme of the genital ridge and form a number of irregularly shaped cords – the primitive sex cords or gonadal cords – that incorporate PGCs. In both sexes these cords are temporarily connected to the surface epithelium. At this time it is still impossible to differentiate the male and female gonad morphologically and they are therefore referred to as indifferent gonads.

Fig. 15-13: Cross section through a bovine fetus of 11.3 cm CRL. 1: Gonad; 2: Mesonephros.

Differentiation of the testis

Differentiation of the testis (Figs 15-14, 15-15) occurs under the influence of the Sry gene (testis-determining factor) on the Y-chromosome. Without the expression of products of this gene, the indifferent gonad develops somewhat later into an ovary. In male embryos, transcripts of the Sry gene only become detectable in the genital ridge just at the onset of testis differentiation. Neither the expression of the Sry gene in the testis primordium, nor subsequent testicular development, is dependent on the presence of germ cells. Sry triggers testis formation by inhibiting Dax-1, a member of the nuclear receptor family, which is also expressed in the indifferent gonad at the same time. The inhibition of Dax-1 is necessary for a genetically male gonad to express its sex phenotypically and develop into a testis.

Fig. 15-14: Schematic drawing showing the topography of the urogenital system after the differentiation of the gonads. 1: Gonad; 2: Giant glomerulus; 3: Tubules of the mesonephros; 4: Mesonephric (Wolffian duct); 5: Paramesonephric (Müllerian) duct; 6: Sinus urogenitalis; 7: Gubernaculum testis; 8: Metanephros; 9: Adrenal gland.

Courtesy Sinowatz and Rüsse (2007).

Fig. 15-15: Testis (1) and epididymis (2) of a bovine fetus with a CRL of 12 cm. 3: Plexus pampiniformis.

Under the influence of the Sry gene, the cells of the primitive sex cords continue to proliferate and penetrate deep into the medulla to form the testicular or medullary cords (Figs 15-16, 15-17). The subsequent development of the indifferent gonad into a testis is initiated in the medullary region of the gonadal ridge. The testicular cords transform into solid tubules composed of primitive germ cells centrally and presumptive sustentacular cells or Sertoli cells peripherally. These tubules are arranged in horseshoe-like loops connected at both ends to a network of tiny cells strands, the later rete testis. The testicular tubules develop a lumen at the time of puberty and become the seminiferous tubules. The rete testis eventually joins the efferent ductules, which are derived from remaining mesonephric tubules. They link the rete testis to the mesonephric or Wolffian duct, which becomes the ductus epididymidis and the ductus deferens.

Fig. 15-16: Testis of a bovine embryo of 10 weeks gestation. The testicular cords consist of primordial germ cells (1) and presumptive Sertoli cells (2). Between the cords mesenchymal cells form the first generation of androgen-secreting Leydig cells (3).

Fig. 15-17: Testis and epididymis of a newborn calf. 1: Testicular parenchyma; 2: Mediastinum testis with rete testis; 3: Tunica albuginea; 4: Corpus epidiymidis; 5: Cauda epididymidis.

The developing male gonad also produces a chemoattractive substance that stimulates the migration of mesonephric cells to the gonad, where they surround the testicular cords and differentiate into the contractile myoid cells. As the testicular cords differentiate, a dense layer of fibrous connective tissue, the tunica albuginea, forms as a capsule surrounding the testicular cords beneath the surface epithelium of the gonad. A tunica albuginea is first seen in cattle at Day 41 (CRL 20 mm), sheep at Day 31 (17 mm CRL), the horse at Day 30 (16 to 17 mm CRL), and the dog at Day 29 (19 to 20 mm CRL).

In the mesenchyme between the testicular cords, the first generation of androgen-producing Leydig cells develop in cattle at a CRL of 30 mm (Day 42) and in pigs at 33 mm. During the next two days, these cells initiate an increasing production of testosterone and androstendione. This endocrine activity is important for the differentiation of the male sexual duct system, the development of the external male genitalia, and differentiation of the sexual centres in the brain, which are important for the development of male behaviour. After several weeks to months (7 months of gestation in cattle), the first (fetal) generation of Leydig cells gradually involutes, to be replaced later by a second generation of Leydig cells before puberty. The second generation cells differentiate from connective tissue cells and are responsible for initiation and further stimulation of spermatogenesis.

Descent of the testes

This refers to the migration of the testes from their intra-abdominal site of development into the scrotum, usually located in the inguinal region (Fig. 15-18). In mammals, this process is subject to species variation. For instance, in aquatic mammals, elephants, and armadillos, the testes remain within the abdominal cavity and descent does not occur. In most mammals, however, including all our domestic species, the testes migrate to an extra-abdominal location. In these species, a temperature of 2–4°C below the core body temperature is required for normal spermatogenesis.

Fig. 15-18: Descent of the testis in cattle. A: The testis is located in the abdominal cavity. B: Testis passing the inguinal canal. C: Testis within the scrotum. 1: Testis; 2: Gubernaculum testis; 2′: Lig. testis proprium and Lig. caudae epididymidis; 2″: Lig. inguinale testis; 3: Wolffian duct; 3′: Epididymis; 3″: Ductus deferens: 4: Ampulla ductus deferentis; 5: Vesicular gland; 6: Prostate; 7: Bulbourethral gland; 8: Urachus; 9: Urinary bladder; 10: Urethra; 11: M. retractor penis.

Courtesy Sinowatz and Rüsse (2007).

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