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Development of the Reproductive System Transcription Factors & Hormones TDF (Testis-Determining Factor) BMP-4 LIF & STEEL Factor Oct-4 Wt-1 & SF-1 Lim-1 Sry Gene Dax-1 Sox-9 Testosterone + Androstenedione hCG MIS (Muellerian-Inhibiting Substance) MIF (Meiosis-Inhibiting Factor) MSF (Meiosis Stimulating Factor) Testosterone Hoxa-10 & 11 Hoxd-11, 12, 13 Hoxd-13 Wnt-4 Wnt-7a Hox, BMP-4, ssh + FGF-4 Ssh, FGF-8 + FGF-10 Testosterone + Dihydrotestosterone Insl-3 REQUIRED for development of phenotypic male. From SRY gene. Inhibits Dax-1. Causes gonadal cords to condense & form seminiferous tubules. Controls formation of germ cells in endoderm of yolk sac & migration into medial UG ridge (day 24) Induce proliferation of germ cells in gonad after migration from endoderm of yolk sac Maintains totopotential state of germ cells (able to grow into any type of cell) Affects somatic cells, NOT germ cells. Needed for the formation of anterior head, kidneys, & gonads On the short arm of the Y chromosome produces TDF Inhibits testis formation Causes growth of gonadal cords into mesenchyme Secreted by fetal Leydig cells differentiation of genital ducts (9-14 weeks) Secreted by placenta, indicating pregnancy. Causes peak of testosterone + androstenedione for the differentiation of genital ducts. Secreted by Sertoli cells involution of the female ducts (paramesonephric ducts degenerate) If testis don’t form properly, can’t secrete MIS. Thus, can be XY with female ducts. Secreted by Sertoli cells Slows growth of primordial germ cells Induces oogonia to enter meiosis. From mesonephric tubule cells associated with rete ovarii. Secreted by Leydig cells. Induces distal mesonephric duct to be highly convoluted epididymis, vas deferens, ejaculatory duct, & seminal vesicles. UG Sinus development. Descent of testis in all 3 phases (Initial, Transabdominal, & Transinguinal) Form epididymis Form vas deferens Determines where the prostate gland develops. Induces budding of endoderm (testosterone-induced mesenchyme below bladder) for prostate gland Necessary for Paramesonephric Duct development. Necessary for Hoxd 10-13 expression. Necessary for external genitalia formation. Necessary for outgrowth of genital tubercle (from genital eminence). Secreted by Leydig cells influences male external genitalia Required for Transabdominal Descent of Testis (Part 2 of Descent). If absent = Bilateral cryptochidism Male vs. Female Structure & Precursor Male Spermatogonia Sertoli cells Seminiferous tubules Straight tubules & Rete testis Efferent ductules Leydig Cells Prostatic Utricle Appendix to Testis Bladder Membranous & Prostatic Urethra Penile Urethra Prostate Gland Bulbourethral glands & Glands of Littre Fossa Navicularis Penile Urethra Penile Raphe Prepuce/Foreskin Corpora Cavernosa & Spongiosa Scrotum Scrotal Raphe Tunica Vaginalis Female Oogonia Follicular cells Stroma cells Primordial follicles Uterine Tubes Uterovaginal Primordium (Uterus & Superior Vagina) Broad Ligament Rectouterine & Vesicouterine Pouches Uterus Superior Vagina Vagina Hymen Greater Vestibular Glands Hydatid (of Morgagni) Remnants of Mesonephric Ducts Clitoris Labia Minora Labia Majora Mons Pubis Vestibule of Vagina Primordial germ cells Mesenchyme Outer portion of gonadal cords Inner portion of gonadal cords Mesonephric tubules Mesenchyme Remnant of paramesonephric duct Remnant of paramesonephric duct Vesical portion of UG sinus Pelvic portion of UG sinus Phallic portion of UG sinus Outgrowth of endoderm (testosterone-induced mesenchyme) just below bladder Endodermal-derived Penile Urethra Ectoderm plate Fusion of urogenital folds posterior to anterior. UG sinus endoderm with surface ectoderm covering the closure. Forms where the fusion of the genital folds occurs. Ectoderm covering. Circular ingrowth of ectoderm around glans of penis. Mesenchyme of the phallus. Mesoderm. From the fusion of the labialscrotal swellings at the midline. Fusion line between the labialscrotal swellings. Remnant of degenerated processus vaginalis. Double layer that encases the testis. Primordial germ cells Cortical cords from mesothelium & mesenchyme from mesonephric tubules. Surface epithelium of the ovary. Mesenchyme surrounding the primordial follicles. Cords break into small clusters with oogonia. Cranial portion of paramesonephric ducts Fusion of the two Muellerian ducts (Paramesonephric ducts) Movement of paramesonephric ducts towards the midline. Movement of paramesonephric ducts towards the midline. Superior part of paramesonephric ducts that fuse together as a solid cord. Wall degenerates to form lumen. Inferior part of paramesonephric ducts that fuse together as a solid cord. Vaginal plate from the fusion of the sinovaginal bulbs. Central cells break for form lumen. Membrane that separates the vaginal opening from the vestibule. Outpocketings of the UG sinus endoderm. Remnant of paramesonephric ducts adjacent to infundibulum. (The only paramesonephric duct remnant). (1) Appendix of Vesiculosa (2) Epoophron (efferent ductules/epididymis) (3) Paraoophoron (4) Gartner Duct Cysts Primordal phallus. Urethra not incorporated b/c UG folds don’t fuse. Unfused UG folds. Unfused Labialscrotal Swellings Labialscrotal Swellings. Phallic portion of UG sinus. Abnormalities of Sexual Differentiation True Hermaphrodites Barr Bodies 70% 46, XX 20% Mosaics 10% 46, XY BOTH Ovarian & Testicular Tissue* Phenotype: Ambiguous genitalia, enlarged clitoris, partially fused labia, amenorrhea Cause: Errors in sex determination Female Pseudohermaphrodites Barr Bodies 46, XX Male Pseudohermaphrodites NO Barr Bodies 46, XY Ovaries Phenotype: Enlarged clitoris, fused labia, persistent UG sinus, possible clitoral urethra (“small penis”) Cause: Excessive androgens = CAH (Congenital Adrenal Hyperplasia) Testes Phenotype: Variable external genitalia (*See AIS), hypoplasia of phallus, paramesonephric ducts (due to low MIS) Cause: Low levels of testosterone & MIS (Defective Leydig cells or receptors) *Androgen Insensitivity Syndrome (AIS): female external genitalia; vagina = blind pouch; absent or primitive uterus/tubes; estrogen for 2 sex characteristics via androgen-converting adrenal cortex; no menstruation; testis in abdomen/inguinal canal; NO Barr Bodies; testis still secrete MIS no duct system; testis removed to reduce risk of tumors Cause: Defect in androgen receptors in genital tubercle, UG folds, & labialscrotal swellings. Socially reared as women.