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Development of male Reproductive System Learning Objectives: At the end of the lecture, students should be able to: • • Know the development of parts of male reproductive system. Know the applied anatomy of development of male reproductive system. DEVELOPMENT OF THE GENITAL SYSTEM: Although the chromosomal and genetic sex of an embryo is determined at fertilization by the kind of sperm that fertilizes the ovum. male and female morphological characteristics do not begin to develop until the week. The early genital systems in the two sexes are similar, therefore the initial period of genital development is referred to as INDIFFERENT STAGE OF SEXUAL DEVELOPMENT. DEVELOPMENT OF THE GONADS : The gonads (testes & ovaries) are derived from three sources; – – – The mesothelium (mesodermal epithelium) lining the posterior abdominal wall. The underlying mesenchyme (embryonic connective tissue). The primordial germ cells. THE INDIFFERENT GONADS During 5th week, when a thickened area of mesothelium develops on the medial side of the mesonephros. Proliferation of this epithelium and the underlying mesenchyme produces a bulge on the medial side of the mesonephros-----the gonadal (genital) ridge. Fingerlike epithelial cords-----THE PRIMARY SEX CORDS soon grow into the underlying mesenchyme. The indifferent gonad now consists of a external cortex and an internal medulla. In embryos with an XY sex chromosome complex, the medulla differentiates into a testes and the cortex regresses, except for vestigial remnants. PRIMORDIAL GERM CELLS • • These large, spherical primitive sex cells are visible early in the 4th week among the endodermal cells of the yolk sac near the origin of the allantois. During folding of the embryo, the dorsal part of the yolk sac is incorporated into the embryo. As this occurs, the primordial germ cells migrate along the dorsal mesentery of the hind gut to the gonadal ridges. During the 6th week the primordial germ cells enter the underlying mesenchyme and are incorporated in the primary sex cords. SEX DETERMINATION Before the 7th week the gonads of the two sexes are identical in appearance and are called INDIFFERENT GONADS. Development of male phenotype requires a Y chromosome, but only the short arm of this chromosome is critical for sex determination. The SRY gene for a TESTES-DETERMINING FACTOR(TDF) has been localized in the sex determining region of the Y chromosome. Two X chromosomes are required for the development of the female phenotype. A number of genes and regions of the X chromosome have special roles in sex determination. The Y chromosome has a testes-determining effect on the medulla of the indifferent gonad. It is the TDF regulated by the Y chromosome that determines testicular differentiation. Under the influence of this organizing factor, the primary sex cords differentiates into seminiferous tubules. The absence of a Y chromosome result in the formation of an ovary. The type of gonads present then determines the type of sexual differentiation that occurs in the genital ducts and external genitalia. TESTOSTERONE produced by fetal testes, that determines MALENESS. Primary female sexual differentiation in the fetus does not depend on hormones. DEVELOPMENT OF THE TESTES: TDF induces the primary sex cords to condense and extend into the medulla of the indifferent gonad, where they branch and anastomose to form the RETE TESTES. The connection of the sex cords----seminiferous cords-------with the surface epithelium is lost when a thick fibrous capsule, the TUNICA ALBUGENIA is the characteristic and diagnostic feature of testicular development. In the fetus gradually they separates from the degenerating mesonephros and become suspended by its own mesentery, the MESORCHIUM. The seminiferous cord develop into the seminiferous tubules, tubuli recti and rete testes. The SEMINIFEROUS TUBULES become separated by mesenchyme that gives rise to interstitial cells of (leydig). By about 8th week, These cells begin to secrete androgen hormones TESTOSTERONE and ANDROSTENEDIONE, which induce masculine, Differentiation of the mesonephric ducts and external genitalia. In addition to testosterone, The fetal testes produces a glycoprotein known as antimullerian hormone (AMH) or mullerian inhibiting substance (MIS). AMH is produced by the sertoli cells, it suppresses development of the paramesonephric ( mullerian ) ducts. The seminiferous tubules remain solid until puberty then lumina begin to develop. The walls of the seminiferous tubules are composed of two kinds of cells. * SERTOLI CELLS---supporting cells derived from the surface epithelium of the testes. * SPERMATOGONIA---primordial sperm cells derived from the primordial germ cells. The rete testes becomes continuous with 15 to 20 mesonephric tubules that become EFFERENT DUCTULES. These ductules are connected with the mesonephric duct, which becomes the DUCTUS EPIDIDYMIS. DEVELOPMENT OF GENITAL DUCTS: Both male and female embryos have two pairs of genital ducts. The mesonephric (wolffian) ducts play an important part in the development of the male reproductive system. And the paramesonephric (mullerian ) ducts have a leading role in the development of female reproductive system. During 5th & 6th weeks, the genital system is in an INDIFFERENT STAGE, when both pairs of genital ducts are present. Under the influence of testosterone produced by fetal testes in the 8th week, the proximal part of each mesonephric duct becomes highly convoluted to form the EPIDIDYMUS. The remainder of this duct forms the DUCTUS DEFERENS and EJACULATORY DUCT. In female fetuses this duct almost completely disappear, only a few non-functional remnants persists. The paramesonephric ducts develop lateral to the gonads and mesonephric ducts and play an essential role in the development of FEMALE REPRODUCTIVE SYSTEM. These ducts form on each side from longitudinal invaginations of the mesothelium on the lateral aspect of the mesonephroi. The funnel-shaped cranial ends of these ducts open into the peritoneal cavity. These ducts pass caudally, parallel to the mesonephric ducts until they reach the future pelvic region of the embryo. Here they cross ventral to the mesonephric ducts, approach each other in median plane, and fuse to form a Y- shaped UTEROVAGINAL PRIMORDIUM. This tubular structure projects into the dorsal wall of the urogenital sinus and produced an elevation, the SINUS ( MULLE RIAN ) TUBERCLE. DEVELOPMENT OF THE MALE GENITAL DUCTS AND GLANDS: The sertoli cells of the fetal testes produce masculinizing hormones e.g. ( Testosterone ) and a mullerian inhibiting substance ( MIS ). These cells begin to produce MIS at 6th to 7th weeks. The interstitial cells begin producing testosterone in the 8th week. TESTOSTERONE, the production stimulated mesonephric ducts to form male genital ducts, where as MIS causes the paramesonephric ducts to disappear by epithelial – mesenchymal transformation. The mesonephric tubules transformed into EFFERENT DUCTULES, DUCTUS EPIDIDYMUS & DUCTUS DEFERENCE. A lateral out growth from caudal end of each duct gives rise to SEMINAL VESICAL, This pair of glands produces a secretion that nourishes the sperms. The part of the mesonephric duct between the duct of this gland and the urethra becomes the EJACULATORY DUCT. PROSTATE Multiple endodermal out growths arise from the prostatic part of urethra and grow into the surrounding mesenchyme, which differentiates into the dense stroma and smooth muscle of the prostate. BULBOURETHRAL GLANDS • • These pea-sized structures develop from paired out-growths from the spongy part of urethra. The smooth muscle fibers and stroma differentiate from the adjacent mesenchyme. The secretions of these glands contribute to the semen. ANOMALIES: Hermaphroditism Androgen insensitivity syndrome (AIS). Mixed gonadal dysgenesis