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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.