Hypothalamic-pituitary-gonadal axis, ovary development, sperm development, oogenesis, sex differentiation, differentiation of internal ducts and external genitalia, testicular descent, cryptorchidism

2 December Hypothalamic-Pituitary-Gonadal Axis Hypothalamus → GnRH → anterior pituitary → FSH, LH Gonads: ovary and testis Somatic cells Sustaining cells Granulosa cells (XX) Sertoli cells (XY) Endocrine cells Theca cells (XX) Leydig cells (XY) Germ cells Oogonia (XX) Ova (X) Spermatogonia (XY) Sperm (X or Y) Ovary Development Primordial follicle Oocyte surrounded by layer of granulosa cells Primary follicle Fully grown oocyte surrounded by zona pellucida and granulosa cells Preantral follicle Oocyte, zona pellucida, granulosa cells, theca, and fluid-filled antrum Mature follicle Oocyte surrounded by zona pellucida and granulosa cells Thick theca Fluid-filled antrum Cumulus oophorous Sperm development Spermatogonium (2n) → mitosis → primary spermatocytes (2n) → first meiotic division → secondary spermatocytes (n) → second meiotic division → spermatids (n) → differentiation and maturation → sperm cells (n) As male germ cells divide, they differentiate as a cohort between the same Sertoli cells in a synchronized fashion. When spermiated into the lumen of seminiferous tubule, spermatozoa are immotile and infertile; they acquire the ability to move and fertilize an ovum during their transit through the epididymis. Tip of sperm – acrosome Sperm are 23, X or Y 22 autosomes + X or Y Oogenesis Oogonia → mitosis, differentiation → primary oocyte During fetal life Primary oocyte → 1 meiotic division (begins in utero, completed prior to ovulation) → secondary oocyte Puberty, first polar body Secondary oocyte → 2 meiotic division (completed after fertilization) → ovum Second polar body 23, X 22 autosomes + X Sex Differentiation (Gonadal Sex) In the XY bipotential gonad, Sry through the actions of Sox9 induces testicular development, and opposes induction of the ovarian development pathway In the XX bipotential gonad, Rspo1 acts through the Wnt4 and β-catenin signaling pathway to promote the ovarian development pathway, and inhibits the testicular development pathway Conventional wisdom holds that the ovary and testis are terminally differentiated organs in adult mammals. It is now known that deletion of a single gene is sufficient to induce transdifferentiation of gonads in adult mice – Fox12 in the ovary and Dmrt1 in the testis – suggesting that development of the gonad to the opposite sex is actively repressed throughout life. Differentiation of Internal Ducts and External Genitalia Which of the two duct systems and types of external genitalia develops depends on the presence or absence of functional fetal testes Bipotential gonad and primitive ducts Bipotential gonad arises from urogenital sinus and remains undifferentiated until ~6 week Wolffian ducts develop in the 4 week and Mullerian ducts in the 6 week th Differentiation of the testis In the genetic male, during 7 week SRY expresses in urogenital ridge cells and triggers differentiation of testes Fetal Sertoli cells secrete Anti-Mullerian Hormone (AMH); also called Mullerian Inhibiting Substance (MIS) Fetal Leydig cells secrete Insulin-like peptide 3 (Insl3) and testosterone Testosterone is converted to dihydrotestosterone (DHT) by 5α-reductase present in target tissues Male phenotype Differentiation of Wolffian (mesonephric) duct Regression of Mullerian (paramesonephric) duct Epididymis, testis, vas deferens, seminal vesicle, prostate, scrotum, penis Female phenotype Differentiation of Mullerian (paramesonephric) duct Ovary, oviduct, uterus, vagina, vaginal vestibule, labia/vulva Differentiation of External Genitalia: Phenotypic Sex Cloaca divides into urogenital sinus and rectum. The urogenital sinus develops into urinary and reproductive organs. The prostate gland develops in tissue of the posterior wall of the urogenital sinus and surrounds the prostatic urethra at the base of the urinary