Sex Determination and Development of the Repro System Flashcards
What is the genetic determinant of sex?
Y chromosome/Absence of Y chromosome
Sex Determining Region of the Y Chromosome (SRY)
- Encodes a transcription factor that regulates the expression of genes on other chromosomes. Turns on genes responsible for testes differentiation and turns off ovarian genes.
Sex Determination
Term used to describe initiation of the Male differentiation pathway by SRY. Once gonadal differentiation is initiated, gonadal hormones then promote sexual dimorphic development of the reproductive tract.
Gonadal Differentiation (before sex differentiation)
- Gonads are derived from the gonadal (genital) ridge, pair of longitudinal ridges, on the medial side of the mesonephros.
- Primary (primitive) sex cords form by proliferation of the surface epithelial cells that penetrate the underlying mesenchyme.
- Gonads are identical in both sexes until 7th week of development.
- Primordial germ cells (PGCs) originate from epiblast-derived cells and are first identifiable in the wall of the yolk sac (~3weeks).
- ~10PGCas first appear bur undergo mitotic divisions en route to the genital ridge (~2000 arrive).
- They then migrate into the genital ridge (5th week) driven by chemotaxis.
- By week 6, the PGCs invade the gonadal ridges and are closely associated with the primitive sex cords. The influence of PGCs on the developing gonad is sexually dimorphic: PGC progression through meiosis is essential for the maintenance of the foetal ovary, otherwise prospective follicular cells degenerate > streak ovaries but testes development is not hindered by lack of germ cells.
- The path of development is determined by presence of SRY
Gonadal Differentiation - Male
- In the 7th week (under the influence of SRY), primitive sex cords proliferate and penetrate the medulla forming “medullary” testis cords.
- Mesodermal cells differentiate into Sertoli cells in the cords under influence of SRY, they aggregate and englose germ cells.
- Mesenchyme tissue in the interstitial spaces develop into Leydig cells and start to secrete testosterone by the 8th week.
- Testis cords become looped - contact with the ingrowing mesonephric tubule called Rete testis.
Gonadal Differentiation - Female
- Female development begins in the 7th week and the absence of SRY leads to the degeneration of medullary/primitive sex cords.
- Cortical cords form from proliferating surface epithelium forming distinct cell clusters.
- Epithelial cells proliferate around each oogonium (germ cell) - forming primordial follicles.
- Germ cells are absolutely required for the formation of the ovarian follicles.
Wolffian (Mesonephric) Ducts
Gives rise to male genital ductal system
Mullerian (Paramesonephric) Ducts
Gives rise to the female genital ductal system
Genetic Control of Genital Duct Development - Male
SRY \/ SOX9 \/ SF1 or other genes \/ Testes \/ Medullary cords develop
Genetic Control of Genital Duct Development - Female
WNT4 \/ DAX1, TAFII 105, FoxL2 \/ Ovaries \/ Medullary cords degenerate and cortical cords develop.
Development of Internal Genitalia - Female
- Lower vagina forms from the paramesonephric tubercle (a region called the sinovaginal bulbs)
- Two evaginations grow out from the pelvic side and proliferate forming the vaginal plate
- By 20 weeks, vaginal outgrowth is complete and expands around the end of the uterus.
Development of External Genitalia
- Initially bipotent. Developmental path taken depends on presence or absence of Androgens.
- No androgens - female
- Androgens - dihydrotestosterone is present - male
Development of Internal Genitalia - Male
- 6 weeks - the WD opens to the urogenital sinus at a site adjacent to the ureteral orifice (UR).
- 7–8 weeks - rather than descent, there are individual variations in the WD position along the mediolateral axis as well as in left/right difference in morphology of the urogenital sinus (URS). The future bladder and urethra are not discriminated in the sinus.
- 8–9 weeks - the bilateral upper angles of the URS start upward growth toward the umbilicus.
- 9 weeks - depending on development of smooth muscles in the bladder as well as rhapdosphincter muscles of the urethra, the descent of the vas deferens becomes evident. However, the epithelium is still same between the future bladder and urethra.
- 10–11 weeks - a drastic upward growth of bladder smooth muscles as well as a developing prostate accelerates the descent of the vas.
Turner Syndrome
45chr. and XO sex determination. Affects 1 in 2000 female births. Oocytes degenerate since 2 “X” chromosomes are needed for full ovarian development leading to a “streak ovary”. Deficiency in ovarian steroids, lack of secondary sex characteristics, short stature, webbed neck and skeletal deformities.
Klinfelter Syndrome
47chr and XXY sex determination. Develop male phenotype. Incomplete virilisation and breast enlargement after puberty. Small testes with decreased spermatogonia.
