Development of the Reproductive System Flashcards
Until what week is the embryo indifferent (no sex)?
week 6
When does sexual differentiation begin?
week 7
When can female and male genitalia be recognized?
week 12
When is phenotypic differentiation complete in the embryo?
week 20
What are primordial germ cells?
progenitor cells of oogonia and permatogoonia
How do primordial germ cells migrate?
–>specified in epiblast, end up in yolk sac wall after gastrulation and body folding
–>migrate up dorsal mesentery to enter genital ridge of intermediate mesoderm
WEEK 5
Describe the location and appearance of primitive gonads during week 6
Initially a pair of longitudinal swelling in urogenital ridges of intermediate mesoderm
–>T10
How are primitive gonads formed?
proliferation and delamination of coelomic epithelium
condensation of underlying mesenchyme
What stimulates formation of somatic support cells?
primordial germ cells
How are somatic support cells formed during week 6?
proliferation and delamination of cells from coelomic epithelium of genital ridge
–> stimulated by primordial germ cells
What eventually differentiate into Sertoli cells in males?
somatic support cells
What eventually differentiates into follicle cells in females?
somatic support cells
What are the 2 sets of reproductive ducts that form within the intermediate mesoderm?
1: mesonephric tubules and duct (wolffian)
2: paramesonpehric duct (Mullerian)
What are the fxns of Wolffian/mesonephric ducts?
form within urogenital ridge
–>early collecting ducts for kidney
–>open into urogenital sinus
What are the fxns of Mullerian/paramesonephric ducts?
ducts form on both sides from invagination of urogenital ridge
–>cranially, open to coelomic cavity
–>caudally, meet with each other and attach to urogenital sinus
What is the key to sexual dimorphism?
Y chromosome
–>contains SRY that codes for testis
*also requires autosomes
What occurs in the absence of SRY gene?
formation of female reproductive organs
What does SRY turn on to drive male repro formation?
days 42-52
+ SOX9 expression in somatic support cells
—>Sertoli cell diff.
suppresses WNT4
–>pro-female gene
What make up testis cords?
-Sertoli cells
surround germ cells
-Primordial germ cells
-Differentiating myoepithelial cells
–>U shaped cords that develop into seminiferous tubules after birth
What are the rete testis?
like testis cords but don’t have germ cells
How are the testis cords linked to developing epididymis and vas deferens?
Testis cord attaches to rete testes–>connected to efferent ductules (remnant of mesonephric tubules)
What are derivatives of the mesonephric duct?
epididymis
vas deferens
Primordial germ cells differentiate into _______
type A spermatogonia 3 months after birth, hault until puberty
What makes fetal Leydig cells?
subset of intertubular cells differentiate into fetal Leydig cells
–>produce testosterone during week 9-10 to influence genital ducts and external genitalia
When do fetal Leydig cells start making testosterone?
weeks 9-10
What cells express anti-Mullerian hormone?
Sertoli cells
What is the fxn of anti-Mullerian hormone?
drives regression of paramesonephric ducts
When are paramesonephric ducts inhibited by anit-mullerian hormone?
weeks 8-10
What do remnants of paramesonephric duct make?
- appendix testis
- prostatic utricle
What do mesonephric tubules and ducts form?
- Efferent ductules from remaining mesonephric tubules
- Epididymis
- Vas deferens
- Seminal vesicles
What drives mesonephric tubule remnants?
Leydig cell-derived testosterone
What is the paradidymis?
remnant of lower mesonephric tubules that are NOT used to make efferent ductules
What drives development of external genitalia?
DHT via 5a-reductase
What does DHT promote formation of?
- penis
- scrotum
- prostate
- ->testicular descent
What drives fetal Leydig cells to produce testosterone?
HCG
What are the fxns of ADULT Leydig cells?
generate androgens–> spermatogenesis
masculinization of brain and male sexual behavior
What regulates testosterone production at puberty?
LH
What germ layer makes up seminal vesicles?
intermediate mesoderm of urogenital ridge
What is formed from buds emanating from the mesonephric duct?
seminal vesicles
What forms from buds emanating from endoderm of urogenital sinus (within future region of pelvic urethra)?
prostate gland
–>week 10
What germ layer makes up prostate gland and bulbourethral glands?
endoderm of urogenital sinus
What forms from endoderm buds?
bulbourethral glands
What is ectodermal-covered mesodermal swelling at distal end of phallic urogenital plate?
genital tubercle
–>growth depends on DHT
How is the urogenital plate formed?
Cloacal membrane ruptures, roof of the phallic segment expands along lower surface of genital tubercle as it enlarges
–>endodermal extension under genital tubercle
What drives lengthening and growth of genital tubercle and fusion of labioscrotal swellings?
DHT
How is the tubular penile urethra formed?
urogenital folds fuse midline from perineal to gland penis
–>converts urethral groove into penile urethra
Where is the urethral groove?
ventral surface of urogenital plate
Where are the labioscrotal swellings in relation to urethral folds?
on either side
What contains gonadal vessels, N, lymph to testis at T10?
suspensory ligament
What connects developing gonad to base of labioscrotal swellings?
gubernaculum
–>eventually shortens to pull testes into scrotum
Describe hypospadias
most common male birth defect after cryptorchidism
–>failure of urethral folds to close properly
*urethral opening on underside of penis instead of tip
Describe epispadias
d/t improper ventral body closure
–>urethra opening on top of penis instead of tip
In absence of SRY, somatic support cells express _________
WNT4 and FOXL2
What is the fxn of FOXL2?
continually suppresses any SOX9 expression
–>maintains female gonad differentiation by continually suppressing Sertoli and Leydig formation
What induces somatic support cells to become follicular cells?
developing oocytes
What is responsible for arresting primary oocytes in prophase 1 of meiosis until puberty?
surrounding follicle cells
Are paramesonpehric ducts retained in males or females?
females
What are the remnants from mesonephric ducts in females?
epoophoron and paraoophoron near ovary
Describe uterine tube formation
Paramesonephric ducts fused at caudal end by week 9-10
- ->fusion of inferior end forms uterus
- ->un-fused portion forms uterine tubes
What are uterus anomalies d/t improper fusion of paramesonephric ducts?
1: Didelphys (double uterus)
2: Bicornate uterus (2 bodies, 1 cervix)
3: Double uterus and double vagina
4: Double uterus
5: Unicornate uterus (1 uterine tube)
6: Septated uterus
What do the paramesonephric ducts form?
uterine tube
uterus
vagina
What is included in external female genitalia?
labia
clitoris
lower vagina
Describe formation of the vagina
Paramesonephric duct contacts urogenital sinus–> prolif and formation of sinuvaginal bulb
sinuvaginal plate lengthens, canalized
What germ layer makes up the vagina (except upper fornix)?
endoderm
Describe vaginal agenesis
Failure of normal sinuvaginal bulb development or canalization d/t agenesis of paramesonephric ducts
What aspects of the phallic segment of urogenital sinus are the same in men and women initially?
urogenital plate
glans plate
genital tubercle
Why is there no lengthening of the genital tubercle or fusion of labioscrotal/urogenital folds in females?
no DHT (via no testosterone)
What forms the labia minora?
urogenital folds
What forms the labia majora?
labioscrotal folds
What separates urethra from vaginal opening?
differential growth and expansion of tissue
What ligament is the portion of gubernaculum between the gonad and uterus?
round ligament of ovary
What ligament is the portion of gubernaculum between the uterus and base of labioscrotal swellings?
Round ligament of uterus
What restricts further ovarian descent?
gubernaculum attachment via round ligaments
What is attached to the ovary during its descent?
suspensory ligament superiorly
gubernaculum connecting gonad to labioscrotal swelling (majora)
What is a double fold of peritoneum (from urogenital ridge) that supports the uterus and ovary?
broad L
mesovarian
mesosalpinx
Describe pathogenesis of 46 XY DSDs
testes but phenotypicallly female
- -> inadequate testosterone synthesis (17B deficienty)
- ->androgen insensitivity syndrome d/t loss of fxn of androgen receptors
- ->5a-reductase deficienty (no DHT)
- ->mutations in anti-mullerian hormone
Describe mutations in AMH that cause DSDs
retention of paramesonephric ducts–>individuals have uterus and uterine tubes along with male ducts and external genitalia
Describe 5a-reductase deficiency in DSDs
AR
- normal testis and duct system
- underdeveloped external genitalia
Describe consequences of androgen insensitivity syndrome
- have testes but no spermatogenesis
- @ puberty, testosterone converted to estradiol to + female secondary characteristics
- produce AMH so no uterus or tubes but vagina is short and ends blindly
- testis found in inguinal or labial regions increases risk of cancer
What is the most common cause of 46 XX DSDs
congenital adrenal hypoplasia
–>deficiency in 21-hydroxylase–>excess ACTH–>excess androgen production
Describe sx of 46 XX DSDs
ovaries
female external genitalia masculinized
–>can look like hypospadias
Describe ovotesticular disorders
- have both testicular and ovarian tissue
- ambiguous external genitalia or predominantly female
- have uterus
**usually karyotype 46XX
What are causes of ovotesticular disorders?
1: Translocation of piece of Y chromosome onto X chromosome
2: subset of cells may have mutation in Y chromosome
3: anomaly in sex determination and differentiation of primordial germ cells
What is associated with extrophy of the bladder?
epispadias
