30. Development of the Genital System Flashcards
What is the general timeline for development of the genital system?
Weeks 1-6 = indifferent embryos
Week 7 = sexual differentiation begins
Week 12 = female and male genitalia can be recognized
Week 20 = phenotypic differentiation complete
Primordial germ cells within the indifferent gonad are thought to arise from _____ cells that end up in the yolk sac wall after gastrulation and body wall folding. They migrate up the _____ ____ to enter the genital ridge around week ____
Epiblast; dorsal mesentery; 5
[they are NOT of endodermal origin]
Around week 6 the primordial germ cells in the indifferent gonad complete their migration to the genital ridge. There are somatic support cells there, which differentiate into _____ cells in males, or ______ cells in females
Sertoli; follicle
What are the 2 genital ducts that develop around week 6-7 of development?
Mesonephric ducts (Wolffian)
Paramesonephric ducts (Mullerian)
Both mesonephric and paramesonephric ducts form in _____ _____ of the urogenital ridge
Intermediate mesoderm
Fate of mesonephric ducts in males vs. females
Males: epididymis, vas deferens, seminal vesicle, ejaculatory duct
Females: degenerates
Fate of paramesonephric ducts in males vs. females
Males: degenerates (appendix of testis, prostatic utricle)
Females: Fallopian tube (oviduct), uterus, upper vagina
Sexual dimorphism is dependent on the ____ chromosome but also autosomes
The ____ gene is the sex-determining region on the above chromosome, it determines gonad type, which determines duct and genitalia development
Y; SRY
In the absence of SRY gene, development is ________. There are also other genes that positively drive this development
Female
The SRY gene is also called _______; it is present on the Y chromosome and is active from 41-52 days. It s expressed in _______ cells and upregulates testis specific genes.
TDF (testis determining factor); somatic support (pre-sertoli)
______ cells surround primordial germ cells in males to organize seminiferous tubules. A subset of intertubular cells differentiate into ________ cells, which are recruited by the cell type mentioned above
Sertoli; fetal Leydig
Sertoli cells express SRY gene, which gives off _______ signal and ________ hormone leading to the regression of _____ ducts between weeks 8-10
Sox9; Anti-Mullerian (aka Mullerian Inhibitory Substance); Mullerian/paramesonephric
Although the mullerian ducts regress between weeks 8-10 in males, they leave behind what 2 small tissue remnants?
Appendix testis
Prostatic utricle
Leydig-derived testosterone drives the mesonephric tubules and ducts to form what 4 major structures in males?
Efferent ductules
Epididymis
Vas deferens
Seminal vesicles
Full degeneration of paramesonephric ducts in males is typically complete by what week of development?
Week 9
What 2 hormones are secreted by sertoli cells driving male differentiation?
AMH —> regression of paramesonephric ducts
Androgen binding factor (binds its receptor on sertoli cells at puberty) —> spermatogonia differentiate into spermatozoa
There are 2 populations of Leydig cells — fetal and adult. The fetal leydig cells are important for male differentiation. They secrete ______ at weeks 8-12, driven by ____ of the placenta, leading to differentiation of the mesonephric duct into the ductus deferens, epididymis, and seminal vesicles. They also secrete _________, which changes testosterone to DHT
Testosterone; HCG; 5-alpha-reductase
DHT is required for:
_________ development into the penis
________ development into the scrotum
_______ development into the prostate
Genital tubercle
Genital swellings
Urethral epithelium
What hormones are secreted by adult Leydig cells that encourage male differentiation?
Androgens — lead to initiation of spermatogenesis, masculinization of brain, male sexual behavior
When do fetal leydig cells regress?
Fetal or early post-natal life
The seminal vesicle buds from the ______ duct, which is composed of _______ of the urogenital ridge
Mesonephric; intermediate mesoderm
The prostate gland buds from the ______ of the urogenital sinus in the region of the pelvic urethra; this occurs around week ____
Endoderm; 10
The bulbourethral glands also develop as ______ buds
Endodermal
The fetus begins with indifferent genitalia, including a ______ ____ which is a remnant of the ruptured cloacal membrane — opening a phallic portion of the urogenital sinus to the exterior, forming an ________-lined plate.
The _______ ____ consists of the remnants of cloacal membrane at the ventral end of the urogenital plate and adjacent ______ ______, which is an ectodermal-covered mesodermal swelling at the ventral and cranial ends of phallic portion of the urogenital plate
Urogenital plate; endodermally
Glans plate; genital tubercle
The genital tubercle is an _______-covered ________ swelling at the ventral and cranial end of phallic portion of urogenital plate
Ectodermal; mesodermal
The tip of the urorectal septum seen at the exterior is known as the __________
Perineal body
The testis start up around ______, and are attached and pulled inferiorly by the _______, eventually anchoring them in the scrotum
T10; gubernaculum
What is the most common urethral birth defect in males after cryptorchidism?
Hypospadias
Epispadias is associated with what other GU birth defect?
Exstrophy of the bladder
In the absence of SRY, development is female. What are 2 other major pro-female genes?
Wnt-4 — initially suppresses SOX-9 expression
FOXL2 — continually suppresses SOX-9, maintaining female gonad (suppresses Sertoli and Leydig differentiation)
In females, somatic cells differentiate into ____ cells and primordial germ cells differentiate into _____, which later differentiate into ____
Follicle; oogonia; oocytes
______ cells surround oocytes. Since there are no Sertoli cells, no ____ hormone is secreted so the _____ ducts are retained. There are also no Leydig cells, so the _____ duct system is lost
Follicle; AMH; paramesonephric; mesonephric
The uterus forms around week ____-____ from fusion of inferior _______ ______
9-10; paramesonephric ducts
The unfused superior portion of the paramesonephric ducts forms the ______ in females
Oviducts
_______ = double uterus
Didelphys
[due to absence of fusion of inferior paramesonephric ducts during development — leading ot double uterus, double vagina, bicornate uterus, septated uterus, unicornate uterus, cervical atresia, etc.]
The vaginal plate is eventually canalized during development. The upper vagina is derived from _____, while the lower vagina is derived from _____
Mesoderm; endoderm
________ = condition characterized by failure of normal vaginal plate development or failed canalization
Vaginal agenesis
Female external genitalia development starts out the same as in males, with the phallic segment of the urogenital sinus forming the urogenital plate, glans plate, and genital tubercle. What happens to these structures in the absence of testosterone or DHT?
No lengthening of genital tubercle occurs; no fusion of labioscrotal swellings
Labioscrotal swellings —-> labia majora
Urogenital folds —> labia minora