Development of Genital System

2. Development of Genital System Ovaries, Fallopian tubes, uterus, Vagina, Vestibular glands, External genitalia Testis, Epididymis, Vas deferens, Seminal vesicle, ejaculatory duct, prostate, bulbourethral glands, External genitalia

3. Development of Genital System ORIGIN • Intermediate mesoderm: Gonads, Ducts • Endoderm of the yolk sac: Primordial Germ cells • Endoderm of the urogenital sinus: Vagina • Surface ectoderm and adjacent mesoderm: External genitalia

4. Sex Determination: Genetic sex of the embryo is determined at fertilization by the kind of the sperm (XX, XY) that fertilizes the ovum. Sex Differentiation (morphological indication of sex): Does not appear until the 7th week.

5. The early genital system is similar in both sexes, and this initial period is referred to as the Indifferent stage of the reproductive organs

6. Development of Genital System • Development of the Gonads: Testes & Ovaries • Development of the Genital Ducts and Auxiliary Genital glands • Development of the External Genitalia

7. Development of The Gonads • The gonads are derived from three sources: • The celomic epithelium (mesothelium) • The underlying mesenchyme • The primordial germ cells

8. Development of Gonads The Indifferent Stage

9. Development of the Indifferent Gonads • First indicated during the 5th week • A gonadal ridge appears medial to the mesonephros, by the: • Thickening of the mesothelium and • Proliferation of the underlying mesenchyme

10. Development of the Indifferent Gonads cont’d • Fingerlike epithelial cords, the primary sex cords, grow into the underlying mesenchyme • The indifferent gonad now consists of an external cortex and an internal medulla

11. Development of the Indifferent Gonads cont’d • During 6th week, the primordial germ cells enter the underlying mesenchyme and are incorporated in the primary sex cords

12. Formation & migration of primordial germ cells • Large spherical cells • Become visible early in 4th week among the endodermal cells of the yolk sac near the origin of allantois • Migrate along the dorsal mesentery of the hindgut to the gonadal ridges

13. Differentiation of Gonads

14. Differentiation of Gonads • Depends on the genetic sex of the embryo • It is the SRY gene for a testis-determining factor (TDF) located in the ‘sex-determining region’ on the short arm of the Y-chromosome critical for the testicular differentiation • Under the influence of TDF, the primary sex cords differentiate into seminiferous cords/tubules of testes • The absence of a Y-chromosome (TDF) results in formation of ovary

15. Differentiation of Sex • The type of gonad (testes or ovary) determines the type of sexual differentiation that occurs in genital ducts and external genitalia • The androgen testosterone, produced by the fetal testes determines maleness • Female sexual differentiation DOES NOT depend on hormones and/or even on the presence or absence of the ovaries. • Absence of testosterone leads to the development of female reproductive system

16. Development of Testes

17. Development of Testes • The primary sex cords become condensed & • Extend into the medulla, where they branch and anastomose to form the rete testes • The seminiferous cords lose connection with the surface epithelium • A thick fibrous sheath, the tunica albugenia, develops and fills the space underthe surface epithelium

18. Development of Testes cont’d • The presence of thick, prominent tunica albugenia is a characteristic feature of testicular development • The seminiferous cords develop into the seminiferous tubules, tubuli recti and rete testis • Later the rete testis become continuous with 15-20 mesonephric tubules, which become efferent ductules

19. Development of Testes cont’d • The seminiferous tubules remain solid until puberty, at which time lumina begins to appear. • The walls of the seminiferous tubules are composed of two type of cells: • Sustentacular (supporting) cells of Sertoli, derived from the surface epithelium and constituting most of the seminiferous epithelium in the fetal testis • Spermatogonia, derived from the primordial germ cells

20. Development of Testes cont’d • The mesenchyme around the seminiferous tubules gives rise to interstitial cells of Leydig. • These cells produce: • Testosteron, which induces the differentiation of male ducts and external genitalia. Testosterone production is stimulated by human chorionic gonadotrophin (hCG) which reaches peak level during 8-12 weeks • Genital duct inducer and suppressor substances, which induce the development of the mesonephric and suppress the development of the paramesonephric ducts

21. Development of Testes cont’d • During later development of testes, the surface epithelium flattens to form the mesothelium on the outer surface of the adult testes • Gradually the enlarging testes separates from the regressing mesonephros and becomes suspended by its own mesentery, the mesorchium

22. Development of Ovaries

23. Development of Ovaries • In embryos lacking Y-chromosome, gonadal development occurs slowly. • The ovary is not positively identifiable until about the 10th week

24. Development of Ovaries • The primary sex cords extend into the medulla and form rudimentary rete ovarii, which ultimately degenerate and disappear. • During early fetal period, a new set of epithelial cords, the secondary sex cords, develop from the surface epithelium and extend into the underlying mesenchyme.

25. Development of Ovaries cont’d • The secondary sex cords remain in the cortex and so are called cortical cord. • The primordial germ cells become incorporated into the cortical cord • At about 16 weeks the cortical cords begin to break up into isolated cell clusters called primordial follicles

26. Development of Ovaries cont’d • Each primordial follicle consists of an oogonium, derived from the primordial germ cell, surrounded by a single layer of flat follicular cells derived from the cortical cord • Active mitosis of oogonia occurs during fetal period producing thousands of primordial follicles • No oogonia formed after birth • Many oogonia degenerate before birth, the remaining ( about 2 million or so) enlarge to become primary oocytes before birth

27. Development of Ovaries cont’d • The surface epithelium becomes separated from the follicles in the cortex by a thin fibrous capsule, the tunica albugenia • After birth the surface epithelium flattens to a single layer of cuboidal epithelium which becomes continuous with mesothelium of the peritoneum • As the ovary separates from the regressing mesonephros, it becomes suspended by its own mesentery, the mesovarium

29. Development of Genital Ducts & the Auxiliary Glands The indifferent stage

30. The IndifferentDucts • Both male and female embryos have two pairs of genital ducts: • The Mesonephric ducts: play an important role in the development of the male reproductive system • The Paramesonephric ducts: play an important role in the development of the female reproductive system

31. The Mesonephric Ducts • The mesonephric ducts drain the mesonephric kidneys • Run caudally and open into the dorsal wall of the urogenital sinus.

32. The Paramesonephric Ducts • Develop on each side from invagination of the celomic epithelium lateral to the mesonephroi • Funnel-shaped cranial ends open into the celomic, or future peritoneal cavity • Passes caudally, parallel to the mesonephric ducts until they reach the future pelvic region

33. The Paramesonephric Ducts cont’d • Cross ventral to the mesonephric ducts, come together in the midline, and fuse to form the uterovaginal canal • This canal projects into the dorsal wall of the urogenital sinus, and produces an elevation , called the Mullerian (sinus) tubercle • The mesonephric ducts open into the urogenital sinus on each side of the tubercle

34. Development of Male Genital Ducts & the Auxiliary Glands • Fetal testes produce musculinizing hormones testosterone and an inducer substance, which stimulates development of the mesonephricducts into the male genital tract, and Mullerian inhibiting substance (MIS) that supresses development of the paramesonephric ducts

35. Fate of Mesonephric Duct in Male • Cranial end persists as appendix of the epididymis, usually attached to head of epididymis • Rest of it gives rise to the epididymis, ductus deferens, seminal vesicle and ejaculatory duct

36. Fate of Mesonephric Tubules in Male • Most of the tubules disappear • Some of the tubules: • Near the testes persist and transform into the efferent ductules. • Caudal to the efferent ductules, may persist as a small body called paradidymis

37. Fate of Paramesonephric Duct in Male Degenerates & disappears. Remnants are: The cranial end may persists as appendix of the testis, which is attached to superior pole of testes

38. Development of Prostate • Begins as multiple endodermal outgrowths from the prostatic part of the urethra, which grow into the surrounding mesenchyme • The glandular epithelium differentiates from this endoderm • The stroma and smooth muscles differentiate from the surrounding mesenchyme

39. Development of Bulbourethral Glands • Develop as paired endodermal outgrowths from the spongy part of the urethra • The stroma and smooth muscles differentiate from the adjacent splanchnic mesenchyme • The secretions of the gland contribute to the semen

40. Development of Female Genital Ducts & the Auxiliary Glands • The mesonephric ducts regress because of the absence of testosterone • The paramesonephric ducts develop because of the absence of MIS, and form most of the female genital tract

41. Fate of Paramesonephric Duct in Female • Unfused cranial parts gives rise to the uterine tubes • The caudal fused portions form the uterovaginal canal, which gives uterus and upper part of vagina • The endometrial stroma and myometrium are derived from adjacent splanchnic mesoderm • A small part of cranial end may persist as hydatid of Morgagni

42. Fate of Mesonephroi in Female • The Mesonephric Tubules: • Some of the mesonephric tubules near ovaries may persist as epoophoron. • Some of the caudal tubules may persist as paroophoron • The mesonephric Duct: • The blind cranial end may persist as an appendix vesiculosa • The caudal part may persist as Gartner’s duct along the lateral wall of the uterus and vagina, and may give rise to Gartner’s duct cyst

43. Formation of The Broad Ligament • Fusion of parameso-nephric ducts results in formation of Broad ligament, Rectouterine and Vesicouterine pouches • Parametrium, composed of loose connective tissue and smooth muscle, develops from mesenchyme between the layers of broad ligament

44. Development of The Vagina • Two sources of origin: • Upper part: from the uterovaginal primordium • Lower part: Vaginal plate from urogenital sinus • Wall: • Epithelium derived from endoderm of urogenital sinus • Fibromuscular wall derived from surrounding mesoderm

45. Development of The Vagina cont’d • Contact of uterovaginal primordium with urogenital sinus induces the formation of paired endodermal outgrowths called the sinovaginal bulbs • Sinovaginal bulbs extend from the urogenital sinus to the uterovaginal primordium • Sinovaginal bulbs fuse to form single vaginal plate

46. Development of The Vagina cont’d • Central cells of vaginal plate degenerate to form the lumen of the vagina • Peripheral cells remain as the epithelium of the vagina • Until late fetal life, lumen of vagina is separated from lumen of urogenital sinus by membrane called hymen • Hymen usually ruptures during perinatal period

47. Development of Auxiliary Genital Glands in the Female • Urethral gland & paraurethral glands of Skene develop as outgrowths from urethra into the surrounding mesenchyme • Greater vestibular glands of Bartholin develop as outgrowth from urogenital sinus

48. Development of External Genitalia • Early development is similar in both sexes • Distinguishing features begin to appear during the 9th week • External genital organs are not fully formed until the 12th week

49. Development of External GenitaliaIndifferent Stage Early in 4th week: • Genital tubercle develops at the cranial end of the cloacal mambrane. It later elongates to form the phalus • Urogenital folds appear on each side of the cloacal membrane • Labioscrotal swellings develop around the urogenital folds

50. Development of External GenitaliaIndifferent Stage • Urorectal septum fuses with cloacal membrane at the end of 6th week • Cloacal membrane divides into anal and urogenital membrane • These membranes rupture a week later to form anus and urogenital orifice, respectively • Urogenital orifice continues on the ventral surface of phallus as urethral groove