Development of the Genital System Flashcards
When does sexual differentiation begin?
week 7
When can genitalia be recognized in utero?
week 12
When is phenotypic differentiation complete in utero?
week 20
How do primordial germ cells develop through week 5?
specified w/in epiblast –> end up in yolk sac wall after gastrulation and body folding –> migrate up dorsal mesentery to enter genital ridge at week 5
What occurs to gonads at week 6?
primordial germ cells migrating to genital ridge
somatic support cells start dividing
What do the somatic support cells develop into?
male –> sertoli cells
female –> follicle cells
What does the mesonephric duct differentiate into?
(male stuff)
epididymis
vas deferens
seminal vesicle
ejaculatory duct
What do the paramesonephric/mullerian ducts differentiate into?
(female stuff)
oviduct
uterus
upper vagina
What do both the mesonephric and paramesonephric ducts arise from?
intermediate mesoderm of the urogenital ridge
What is the SRY gene?
on Y chromosome
expressed in somatic support cells –> upregulates testis-specific genes
sertoli cells organize seminiferous tubules
make paramesonephric ducts degenerate
When is SRY gene active?
days 41-52
What do fetal leydig cells arise from?
sertoli cells recruit intertubular cells –> fetal leydig
What specific genes does SRY turn on?
SRY –> Sox9 –> Anti-Mullerian Hormone (AMH)
In a male, when do the mullerian ducts degenerate?
weeks 8-10
What are the remnants of the mullerian duct in males?
appendix testis
prostatic utricle
What do adult leydig cells do?
produce androgens –> initiate spermatogenesis
masculinize brain
What does 5 alpha reductase do?
converts testosterone –> dihydrotestosterone
What does the seminal vesicle arise from?
buds off of mesonephric duct = intermediate mesoderm of urogenital ridge
What do the prostate and bulbouretral glands arise from?
prostate = endoderm of UG sinus week 10
bulbouretral glands from endodermal buds
What does the genital tubercle arise from?
ectodermal-covered mesoderm
How does the male external genitalia arise?
cloacal membrane ruptures –> phalic portion of urogenital sinus open to exterior –> urogenital plate forms at roof (endoderm)
glans plate = remnants of cloacal membrane at ventral end or urotenital plate (endoderm)
How are the urogenital groove and fold related to male external genitalia?
In 7th week perineum made of urogenital groove, w/ urogenital fold lateral (glands plate still present) –> fold eventually elongates and surrounds the groove
What does DHT do to the developing penis?
drives lengthening and growth of genital tubercle and fusion of labioscrotal swellings to form scrotum
urethra closed by week 14
What is contained in the suspensory ligament of the testes?
gonadal vessels, nerves, lymphatics
How do the testes descend?
start at T10 –> gubernaculum attached to scrotum and pulls them down
What is hypospadias?
urethra on ventral side of penis
0.5% of all births
What is epispadias?
urethra opens on dorsal side of penis
1:120000
associated w/ exstrophy of bladder
body folding issue?
What occurs genetically to induce the ovary?
no SRY –> WNT-4 expressed –> FOXL2 suppresses SOX9
promotes female genetalia
What do oocytes develop from?
primordial germ cells –> oogonia –> oocytes
What do follicle cells do?
somatic cells –> follicle cells
surround oocytes and block them in meiosis I
What happens to the duct system in the developing female?
no sertoli cells –> no AMH, so paramesonephric/mullerian ducts retained
no leydig cells so mesoneprhic duct system is lost
How does the uterus form and at what time?
inferior paramesonephric/mullerian ducts fuse
weeks 9-10
*uterine tubes are unfused superior portion of mullerian ducts*
What are the 6 discussed uterus anomalies?
double uterus, double vagina
double uterus
bicornate uterus
septated uterus
unicornate uterus
cervical atresia
How does the vagina form?
sinovaginal bulb fromed from endoderm at 10th week
begins to elongate and canalize –> finished w/ hymen at 20 weeks
upper vagina = mesoderm
lower vagina = endoderm
How does the female external genitalia form?
beginning is same = urogenital plate, glans plate, and genital tubercle
no Testosterone –> no DHT –> no lengthening of genital tubercle, no fusion of urogenital folds or labioscrotal swellings
genital tubercle becomes clitoris
How does the broad ligament form?
midline fusion of mullerian ducts –> lower urogenital ridge within pelvic cavity and is covered w/ peritoneum
when uterus and oviducts are finished, remaining tissue thins = double fold of peritoneum supporting uterus and ovary
What do the parts of the gubernaculum develop into in the female?
superior part –> round ligament of ovary (ovary to uterus)
inferior part –> round ligament of uterus (uterus to labia majora)
What are disorders of sex development (DSD)?
development of chromosomal, gonadal, and anatomic sex is atypical (1:5000)
46, XY DSDs
genotype = male, has testis, but phenotype is female
causes:
inadequate T synthesis (17 beta dehydrogenase defect)
androgen insensitivity
5 alpha reductase deficiency
mutations in AMH or AMH receptor
Androgen insensitivity syndrome
common cause is loss of functional androgen receptors (X-linked recessive, 1:20000)
have testis by no spermatogenesis
at puberty, T–> estradiol –> female secondary traits form
produce AMH, so no uterus or uterine tubes, vagina short and ends blindly
increased risk of testicular cancer
5 alpha-reductase deficiency
46, XY genotype
AR inheritence
normal testis and duct system
underdeveloped male external genitalia
Female DSDs
46, XX genotype
have ovaries, but masculine external genitalia
most common cause = congenital adrenal hyperplasia
Ovotesticular disorders
true intersexuality
both testes and ovarian tissue
causes: translocation of a piece of Y onto X (barr body causes mosaicism)
subset of cells may have Y mutation
anomaly in sex determination and differentiation of primordial germ cells
What is distinct about GnRH’s action on the ant pit?
upregulates its own receptor in the ant pit
in add’n to promoting LH and FSH secretion