4. Sex determination Flashcards
Define sex determination
Sex determination - process of development of sex differences - phenotypic development of structures upon hormone action produced after gonadal determination
How many genes are in X/Y chromosome
X ~800-1000 genes
Y ~78 genes
What determines the sex of the offspring?
Father - X/Y sperm
What is bipotential indifferent stage?
A reproductive organ until week 7 of development which is sexually undetermined - has the potential to develop into two fates: ovary/testis
What are the main reproductive cells?
Germ cells in gonads: oocyte / sperm
Somatic cells in gonads: granulosa, theca / Sertoli, Leydig
Explain what are primordial germ cells
PGCs:
- precursor of egg / sperm
- large spherical sex cells
- specification of PGCs into eggs / sperm around week 3
- PGCs first located outside the embryo - in yolk sac - migrate into embryo gonadal / genital ridge
Describe how PGCs migrate
Migration: PGCs migrate into genital ridge: through hindgut -> dorsal mesentry -> genital ridge
Proliferation: mitosis while migrating from ~100 -> 25000 cells -> divide into two populations - colonise left + right gonads
What is the fetal kidney system?
Fetal interim kidney - mesonephros - later degenerates -> develop normal adult kidneys
What does PGC motility require?
PGC motility requires:
- chemotaxis signals (TGFβ, Kit ligand/SCF, bFGF)
- gradients of ECM glycoproteins
- PGC-PGC contact
Sex specific PGC differentiation begins only after gonad colonisation - PGC -> prespermatogionia/prospermatogonia or oogonia
What is the main gene regulating gonadal development beyond indifferent stage?
Steroidogenic factor 1 gene (SF1) - in SF1 KO mice gonads fail to develop beyond indifferent stage
What are the main steps of sexual development?
Primary sex determination
Secondary sex differentiation
What is the Jost paradigm?
Jost paradigm - default sex development - female
Alfred Jost - removed ovaries / testis from fetal rabbits - allowed to develop in utero - both developed into female - when injected testosterone - developed into males
=> sexual dimorphisms arise because fo testicular hormone production
What are the hormones produced by testis that drive male development?
- Testosterone - secreted by Leydig cells
- Anti-Mullerian hormone (AMH) - secreted by Sertoli cells
How does female reproductive system develop from indifferent bipotential stage?
Wolffian duct regresses because no testosterone or AMH
How does male reproductive system develop from indifferent bipotential stage?
Mullerian duct has AMH receptors - when AMH released from Sertoli cells - signal for Mullerian duct regression
PGC development overview
What gene determines the sex of the organism?
SRY gene on Y chromosome - initiates testis development - encodes genetic TF - expressed in male somatic cells - Sertoli cells
Needed at a specific time window - only induces testis development if SRY expressed E10.5-12.5
What happens if XY KO SRY gene?
XY KO SRY develops into female but with reduced fertility / infertile
What happens if XX KI SRY gene?
XX KI SRY develops into male but no sperm - more male specific genes required from Y chromosome than just SRY
If SRY gene codes for TF - what is the target?
SRY TF target - SOX9 gene - induces testis development
What is needed for AMH expression in Sertoli cells?
SRY TF -> SF-1 TF -> AMH expression
Male sex determination summary
It is thought that female sex determination is default but what made question
Now not known any gene that would specifically produce ovaries - but XY twins born with X duplicated DAX1 gene -> develop into females
Which gene is important for ovarian development?
Evidence for β-catenin signalling induced by Wnt4 - expression maintained in ovaries
XY with duplication of Wnt4 overexpress DAX1 and develop ovaries
What are the three types of disorders of sex development (DSD)?
DSD types:
- sex chromosome: numerical / structural problems - Turner (XO), Klinfelter
- 46 XX: androgen excess in pregnancy - XX develops as male
- 46 XY: defect in steroidogenesis - abnormal testis development - ex: 5a reductase deficiency - if born female in puberty develops male characteristics
What type of sex determination is in humans vs ants/flies vs turtles/alligators?
Humans - chromosomal sex determination - XX/XY
Flies - ratio of sex X chromosomes:autosomes
Ants - fertilized diploid eggs = females, unfertilized haploid eggs = males (males don’t have fathers, only mothers)
Turtles / alligators: environmental determinants: sex determined after fertilization by the env - temperature during specific developmental time window
What is an example of environmental sex determination?
What is an example of sex reversal?
What is the cause why sea turtle populations have become increasingly female?
Thermosensitive sex determination - global warming - at higher temp females develop
