Development of the Genital System Flashcards
Overall timeline of sexual differentiation Wks 1-6 Wk 7 Wk 12 Wk 20
1-6: indifferent embryo
7: sex diff begins
12: F and M genitalia can be recognized
20: phenotypic diff complete
Describe the path of the primordial germ cell in the indifferent gonad
- germ cells specified within epiblasts
- after gastrulation and body folding, they end up in the yolk sac wall
- they migrate up the dorsal mesentery to enter the genital ridge
What somatic support cells, found in the 6 wk indifferent gonad, differentiate ultimately into what (M and F)?
M: Sertoli
F: follicle
What type of ‘derm’ do both ducts (parameso- and meso- nephric) form from?
intermediate mesoderm of the urogenital ridge
What are the ultimate structures of the mesonephric duct?
epididymis
vas deferens
seminal cesicle
ejaculatory duct
What are the ultimate structures of the paramesonephric duct?
oviduct
uterus
upper vagina
What is the gene of the sex-determining region of the Y chromosome?
SRY gene
Sexual dimorphism depends on what 2 things? (one specific, one general)
Y chromosome
but also some autosomes
What is the importance of the SRY gene?
determines gonad type, which determines duct and genitalia development
What two factors determine F development? (general)
absence of SRY
also genes that positively drive F development
SRY Gene:
- which chromosome?
- active during what days?
- expressed in what cells?
- AKA?
- function?
Y Chrm 41052 days somatic support cells (pre-Sertoli) TDF: testis determining factor upregulates testis-specific genes
How do seminiferous tubules organize?
Sertolis surround primordial germ cells
What do Leydig cells differentiate from?
subset of intertubular cells
What do Sertoli cells contribute to male diff?
Anti-Mullerian Hormone: regression of paramesonephric ducts
androgen binding factor: spermatogonia –> spermatozoa
What are the contributions to male diff made by fetal Leydig cells?
-testosterone; weeks 8-12; driven by hCG of placenta
mesonephric duct –> ductus deferense, epididymis, seminal vesicle
5 alpha-reductase (T –> DHT):
genital tubercle –> penis
genital swellings –> scrotum
urethral epithelium –> prostate
What are the contributions that adult Leydig cells make to male diff?
drives androgens –>
initiation of spermatogenesis
“masculinization” of brain
male sex behavior
What does the seminal vesicle bud from?
mesonephric duct (intermediate meso of UG ridge)
What does the prostate gland bud from?
endoderm of UG sinus in region of pelvic urethra
week 10
Where do the bulbourethral glands come from?
endodermal buds
How does the UG plate form?
remnants of the cloacal membrane opens phallic portion of UG sinus to exterior
plate lined w/ endoderm
How does the glans plate form?
from remnants of the cloacal mem at the ventral end of the UG plate and the adjacent genital tubercle
What is the genital tubercle?
extodermal-covered mesodermal swelling at ventral and cranial end of the phallic portion of the UG plate
Epispadias are associated with what other condition?
Exstrophy of the bladder
What factor is SUPPRESSED to allow female gonadal diff?
SOX-9
How is Sox-9 initially suppressed?
No SRY, allowing Wnt-4 to suppress Sox-9 expression
After Wnt-4, what suppressed SOX-9?
FOXL2 continualy suppresses SOX-9, maintaining female gonad
in F, primordial germ cells differentiate into what?
and those proliferate, then differentiate into what?
oogonia; oocytes
Oocytes surround what?
follicle cells
Since F do not have Sertoli’s, what hormone is ABSENT, and what structure is RETAINED?
Anti-Mullerian Hormone
paramesonephric ducts aka Mullerian ducts
What do Mullerian (parameso) ducts differentiate into? (3)
Fallopian tubes
Uterus
Upper vagina?
When and how does the uterus form?
When: wk 9-10
how: fusion of inferior Mullerian (parameso) ducts
What are oviducts made from?
unfused superior portion of the Mullerian (parameso) ducts
Term for double uterus?
didelphys
What is the upper vagina derived from?
mesoderm
What is the lower vagina derived from?
endoderm
What two factors can lead to vaginal agenesis?
either failure of normal vaginal plate development OR failed canalization
What 3 structures make up the phallic segment of the urogenital sinus?
UG plate
glans plate
genital tubercle
What embryo structure –> roung lig of ovary? Connects what to what?
superior gubernaculum
ovary to uterus
What embryo structure –> roung lig of uterus? Connects what to what?
inferior gubernaculum
uterus to labia majora
Rudimentary stromal cells –> M and F?
M: Leydig
F: thecal cells
Rudimentary gubernaculum –> M and F?
M: gubernaculum testis
F: Round ligs X 2
Rudimentary parameso ducts –> M and F?
M: mostly gone, but leaves behind appendix of testis and prostatic utricle
F: fallopian tubes, uterus, vagina
Rudimentary UG sinus –> M and F?
M: prostatic + membranous urethra; prostate gland; bulbourethral glands
F: membranous urethra, urethral/paraurethral glands, greater vestibular glands
Rudimentary genital tubercle –> M and F?
M: glans penis, corpora cavernosa, corpus spongiosum
F: glans clitoris, corpora cavernosa, bulbospongiosum of vestibule
Rudimentary UG folds + UG and glands plates –> M and F?
M: penile urethra/ventral part of penis
F: labia minora
Rudimentary labioscrotal folds –> M and F?
M: scrotum
F: labia majora
What is pseudohermaphroditism (aka disorders of sex development, DSD)?
genotypic sex is masked by pheno appearance resembling opposite sex, or having repro organs of the opposite sex
What is the phenotype of a 46 XY DSD?
What are 4 causes of this?
female
- inadequate T synthesis
- androgen insensitivity syndrome
- 5 alpha reductase deficiency
- mutations in AMH or AMH receptor
Describe Androgen Insensitivity Syndrome
46 XY DSD, so female phenotype
common cause: loss of functional androgen receptors
X linked recessive
have testis, but no spermatogenesis, w/ poss high T levels
testes found in inguinal or labial regions
@ puberty, T –> estradiol –> female sex traits + amenorrhea
AMH+, so parameso system is suppressed
no uterus or tubes
vagina is short + blind ended
risk of tumors and malignancies
Describe 5 alpha reductase deficiency
46 XY genotype autosomal recessive normal testis and duct system underdeveloped male external genitalia depending on level of deficiency, CAN have F external pheno
Female DSDs = 46 XX
- what gonad do they have
- what happens in fetal life to lead to symptoms?
ovaries
fetus produces excess androgens –> masculinization of female external genitalia
*fusion of labia gives appearance of scrotum
What is the most common cause of female sexual ambiguity?
Congenital adrenal hyperplasia
specifically 21 hydroxylase
Describe Ovotesticular Disorders (True Intersexuality)
- have both testicular and ovarian tissue
- ambig genitalia or predom female
- uterus +
**true sex = what they can best adapt to in society
3 causes of ovotesticular disorders?
- translocation of Y onto X (Barr body causes mosaicism)
- subset of cells w/ mut in Y
- anomaly in sex det and diff of primordial germ cells
