The Legendary Genius..

Development of Gonads - During 5 th week: gonadal development occurs. - Until 7 th week: gonads are similar in both sexes.

Development of Gonads Mesothelium (mesodermal epithelium lining the coelomic cavity) 1 Underlying mesenchyme 2 Primordial germ cells 3 Gonads are derived from 3 sources :

Indifferent Gonads

 the initial period of genital development is referred to as the indifferent stage of sexual development.  The initial stages of gonadal development occur during the fifth week ( 5 th )

A thickened area of mesothelium develops on the medial side of the mesonephros Gonadal ridge: a bulge on the medial side of mesonephros produced by: Proliferation of mesothelium (cortex) Proliferation (condensation ) of mesenchyme (medulla)

Finger like epithelial cords or Gonadal cords soon grow into the underlying mesenchyme

The indifferent gonad now consists of: 1- an external cortex 2 - an internal medulla

Indifferent Gonads  In embryos with an XX sex chromosome complex, the cortex differentiates into an ovary and the medulla regresses  In embryos with an XY sex chromosome complex, the medulla differentiates into a testis and the cortex regresses  Except for vestigial remnants.

Primordial Germ Cells

These large, spherical cells are visible early in the fourth week among the endodermal cells of the yolk sac near the allantois During folding of the embryo, the dorsal part of the yolk sac is incorporated into the embryo the primordial germ cells migrate along the dorsal mesentery of the hindgut to the gonadal ridges

Primordial Germ Cells  During the sixth week the primordial germ cells enter the underlying mesenchyme and are incorporated in the gonadal cords o The migration of the primordial germ cells is regulated by the genes : 1- stella 2- fragilis 3- BMP-4. o If they fail to reach the ridges, the gonad remain indifferent or is absent…

Sex Determination

 Chromosomal and genetic sex is determined at fertilization  It depends upon whether an X-bearing sperm or a Y-bearing sperm fertilizes the X- bearing ovum  The type of gonads develop is determined by the sex chromosome complex of the embryo (XX or XY)

Sex Determination  Before the seventh week, the gonads of the two sexes are identical in appearance called indifferent gonads  Development of the male phenotype requires a Y chromosome  The SRY gene for a testes-determining factor (TDF) has been localized in the sex-determining region of the Y chromosome ( on the short Arm of this chromosome )  Two X chromosomes are required for the development of the female phenotype

Sex Determination  The Y chromosome has a testes-determining effect on the medulla of the indifferent gonad  The absence of a Y chromosome results in the formation of an ovary  Testosterone, produced by the fetal testes, determines the maleness  Primary female sexual differentiation in the fetus does NOT depend on hormones  It occurs even if the ovaries are absent  Expression of the Sox9 and Fgf9 genes is involved in the formation of the seminiferous cords.

Development of Testes

 Embryos with a Y chromosome usually develop testes  The SRY gene for TDF on the short arm of the Y chromosome acts as the switch that directs development of indifferent gonad into testes

TDF induces the gonadal cords to condense and extend into the medulla of indifferent gonad, where they form rete testes

The connection of gonadal cords or seminiferous cords with the surface epithelium is lost as tunica albuginea develops

Development of Testes  The development of a dense tunica albuginea is the characteristic feature of testicular development in a fetus

The enlarging testis separates from the degenerating mesonephros and becomes suspended by its own mesentery called mesorchium The seminiferous cords develop into the seminiferous tubules, tubuli recti, and rete testis

The seminiferous tubules are separated by mesenchyme that gives rise to the interstitial cell of Leydig

Development of Testes  By the eighth week, these cells(Leydig) begin to secrete testosterone and androstenedione  These hormones induce masculine differentiation of the mesonephric ducts and external genitalia  Testosterone production is stimulated by HCG which reaches peak amounts during the 8- to 12-week period.  Fetal testes also produces a glycoprotein called antimullerian hormone (AMH) or mullerian inhibiting substance (MIS)

AMH is produced by sustentacular cells of Sertoli

AMH suppresses development of the paramesonephric ducts Seminiferous tubules remain solid until puberty

Development of Testes  The walls of seminiferous tubules are composed of two kinds of cells :

1.Sertoli cells, supporting cells derived from the surface epithelium on the testis 2. Spermatogonia, primordial sperm cells derived from the primordial germ cells

The rete testis becomes continuous with 15 to 20 mesonephric tubules that become efferent ductules - These ductules are connected with the mesonephric duct - It becomes the duct of the epididymis

In Summary …

Development of Genital Ducts

 Both male and female embryos have two pairs of genital ducts  The mesonephric ducts (wolffian ducts) play an important role in the development of the male reproductive system  The paramesonephric ducts (mullerian ducts) have a leading role in the development of the female reproductive system  Till the end of sixth week, the genital system is in an indifferent state, when both pairs of genital ducts are present

Distal to the epididymis, the mesonephric duct acquires a thick investment of smooth muscle and becomes the ductus deferens A lateral outgrowth from the caudal end of each mesonephric duct gives rise to the seminal gland or vesicle The secretion from this pair of glands nourishes sperms The mesonephric duct between the duct of this gland and the urethra becomes the ejaculatory duct

Prostate  Multiple endodermal outgrowths arise from the prostatic part of the urethra  Grow into surrounding mesenchyme  The glandular epithelium of the prostate differentiates from these endodermal cells  The associated mesenchyme differentiates into the dense stroma and smooth muscle of the prostate

Bulbourethral Glands  pea-sized structures develop from paired outgrowths from the spongy part of the urethra.  The smooth muscle fibers and the stroma differentiate from the adjacent mesenchyme.  The secretions of these glands contribute to the semen.

Development of External Genitalia

 Up to the seventh week of development the external genitalia are similar in both sexes  Distinguishing sexual characteristics begin to appear during the ninth week  External genitalia are not fully differentiated until the twelfth week

Early in the fourth week, proliferating mesenchyme produces a genital tubercle in both sexes at the cranial end of the cloacal membrane Labioscrotal swelling and urogenital folds soon develop on each side of the cloacal membrane The genital tubercle soon elongates to form a primordial phallus

Development of External Genitalia  When the urorectal septum fuses with the cloacal membrane, it divides it into : 1. A dorsal anal membrane 2. A ventral urogenital (Urethral) membrane

The urogenital membrane lies in the floor of a median cleft, the urogenital groove, which is bounded by urogenital folds

Development of Male External Genitalia

 Masculization of the indifferent external genitalia is induced by testosterone

The phallus enlarges and elongates to become the penis The urogenital folds form the lateral walls of the urethral groove on the ventral surface of the penis to form the spongy urethra

The surface ectoderm fuses in the median plane of the penis, forming a penile raphe and enclosing the spongy urethra within the penis

At the tip of the glans of the penis, an ectodermal ingrowth forms a cellular ectodermal cord It grows towards the root of the penis to meet the spongy urethra

Development of Male External Genitalia  This cord canalizes and joins the previously formed spongy urethra  This completes the terminal part of the urethra and moves the external urethral orifice to the tip of the glans of the penis  During the twelfth week, a circular ingrowth of ectoderm occurs at the periphery of the glans penis

Development of Male External Genitalia  When this ingrowth breaks down, it forms the prepuce (foreskin)  It is adherent to the glans for some time  Usually not easy to retract at birth  Corpora cavernosa and corpus spongiosum of the penis develop from mesenchyme in the phallus

The labioscrotal swellings grow towards each other and fuse to form the scrotum The line of fusion of these folds is clearly visible as the scrotal raphe

Development of Male External Genitalia  Agenesis of scrotum is an extremely rare anomally

Development of Inguinal Canals  Inguinal canals develop in both the sexes

The gubernaculum passes obliquely through the developing anterior abdominal wall at the site of future inguinal canal The gubernaculum attaches caudally to the internal surface of the labioscrotal swellings

The processus vaginalis develops ventral to the gubernaculum and herniates through the abdominal wall along the path formed by the gubernaculum

Development of Inguinal Canals  The vaginal process carries extensions of the layers of the abdominal wall before it, which form the walls of the inguinal canal

In males, these layers also form the coverings of the spermatic cord and testis The opening in the transversalis fascia produced by the vaginal process becomes the deep inguinal ring The opening created in the external oblique aponeurosis forms the superficial inguinal ring

Testicular descent is associated with: Descent of Testes 1 Enlargement of the testes and atrophy of the mesonephroi, allow caudal movement of the testes 2 Atrophy of paramesonephric ducts enables testes to move transabdominally to the deep inguinal rings 3 Enlargement of processus vaginalis guides the testes through the inguinal canal into the scrotum

Descent of Testes  By 26 weeks the testes have descended retroperitoneally to the deep inguinal rings  This change in position occurs as the fetal pelvis enlarges and the trunk of the embryo elongates  Little is known about cause of testicular descent  The process is controlled by androgens

Descent of Testes  Passage of testis through the inguinal canal may also be aided by the increase in intra- abdominal pressure resulting from growth of abdominal viscera  Descent of testes through the inguinal canals into the scrotum usually begins during 26 th week  It takes 2 to 3 days

Descent of Testes  More than 97% of full-term newborn males have both testes in the scrotum  During the first 3 months after birth, most undescended testes descend into the scrotum  Spontaneous testicular descent does not occur after the age of one year  When the testis descends, it carries its ductus deferens and vessels with it

DESCENT OF TESTIS  Fate of gubernaculum testis: degenerates & disappears  Fate of processus vaginalis: During perinatal period: 1. The stalk normally obliterates 2. The caudal part forms the peritoneal sac surrounding the testis (tunica vaginalis)

ANOMALIES Female ducts in male:  Paramesonephric ducts develop in male (it should disappear in males )  Cause: failure of development of testes & absence of müllerian inhibiting substance

ANOMALIES Hypospadius:  Most common anomaly of penis  Causes: inadequate production of androgens and/or inadequate receptor sites for hormones  External urethral orifice opens on ventral surface of glans or body of penis (80% of cases) Why ?  due to failure of canalization of ectodermal cord in glans and/or failure of fusion of urogenital folds  In perineal hypospadius: labioscrotal swellings fail to fuse & the orifice is located between unfused halves of scrotum

ANOMALIES Cryptorchidism (undescended testis):  Occurs in up to 30% of premature males and in approximately 3% to 4% of full-term males.  Cause: deficiency of androgens  May be unilateral or bilateral  In most cases, testes descend by the end of 1 st year, if not, atrophy occurs.  Men with a history of cryptorchidism have an increased risk of developing testicular cancer. (risk of developing germ cell tumors, especially in cases of abdominal cryptorchidism. )  Cryptorchid testes may be in the abdominal cavity or anywhere along the usual path of descent of the testis, but they are usually in the inguinal canal

CHRYPTORCHIDISM