Sexual differentiation, Reproductive hormones and gametogenesis Flashcards
(164 cards)
What is the sex cascade?
Genetic sex
Gonadal sex
Somatic sex
Brain sex
Define sex
The process by which a genetically novel individual is formed as the result of mixing of genes from two or more individuals
Why do we need sex?
Recombination and allelic assortment helps to generate variation in populations that allows adaptation to changing selective pressure
Name a species where the female is heterogametic
Chickens - ZW system
What determines gonadal sex?
Genetic sex of indifferent gonad via paracrine peptide hormones and small endocrine molecules around the body
XO
Turner’s syndrome
Ovary
XXY
Kleinfelter’s syndrome
Testis
XXSxr
X-Y translocation
Testis
XY/
Deletion of part of Y
Ovary
Describe X inactivation
All but one X inactivated to prevent OD of genes carried on X
Lyonisation to produce Barr bodies
Done on a random basis amongst cells in epiblast at the primitive streak stage
What is the key gene determining the effect of the Y chromosome?
SRY
Sex determining region of y
Describe SRY
Size
Effector region
Effects
223 aa
Highly conserved DNA binding domain of 79 aa called an HMG box (high mobility group of proteins)
HMG box binds both DNA and RNA, affecting their accessibility and stability
Affects expression of a number of other genes e.g. SOX9 involved in gonad differentiation
Describe formation of the genital ridges
W5 and 6
Colonised by primordial germ cells migrating from extraembryonic mesoderm to caudal part of the yolk sac and then onto the dorsal mesentery and upwards to genital ridges
Ridges run parallel either side of gut
Coelomic epithelium proliferates to form primitive sex cords
Initially bipotential with both sets of ducts
How did the Y chromosome develop?
Acquisition of a male-determining gene to form a proto-Y chromosome
Further acquisition of antagonistic mutations, aided by a series of inversions suppresses opportunities for recombination
Lack of recombination leads to accumulation of repetitive sequences
How do germ cells form in humans?
Differentiate from amniotic ectoderm under influence of BMP4 produced in autocrine fashion by amnion and WNT3A from overlying cytotrophoblast
Name the TFs produced by the amnion
OCT4
NANOG
SOX2
What is the embryo called when it is bipotential with respect to gonads?
Indifferent gonad stage
What happens when primitive germ cells arrive at the genital ridges in females?
Female: No SRY. Default pathway.
Coelomic epithelium proliferates to form cortical sex cords. Stromal cells from cortical cords surround oogonia to form primary follicles.
Paramesonephric ducts grow due to lack of MIS, fusing together inferiorly and with the urogenital sinus to form the Fallopian tubes, uterus and top of vagina.
Mesonephric ducts degenerate due to lack of androgens.
What happens when primordial germ cells reach the genital ridge in males?
Male: SRY switched on in coelomic epithelial cells of sex cord (Sertoli cells), which proliferate to form seminiferous tubules.
SRY switched on in stromal cells (Leydig cells) which start to produce androgens.
Androgens maintain the mesonephric duct
Sertoli cells make MIS Mullerian Inhibitory Substance that makes the paramesonephric ducts degenerate.
What are the messengers released by the testis to mediate somatic sex?
- Androgens –> penis, scrotum, vasa, accessory sex glands
Testosterone processed by 5 alpha reductase present in local tissues, produces dihydrotestosterone DHT, which drives differentiation of external genitalia. - Insulin-like hormone 3 –> gubernaculum contraction –> testis descent
- MIS –> uterine primordium regresses in males
What is it called when genetic and gonadal sex males develop female genitalia? What causes it?
Guevadoces Lack 5alpha reductase Cannot make DHT At puberty extreme virilisation as testosterone levels rise Urethra continues to open near anus
How does female somatic sex develop?
Absence of androgens results in lack of closure of urogenital folds.
What is the difference between male and female brains?
- Structural - sizes
- Chemical - transmitter levels
- Physiological - metabolism, cyclicity
- Psychological - gender, aggression
- Cognitive - verbal fluency, spatial ability
How can you artificially masculinise a brain? What does that tell us?
Administer testosterone to females within first few days of birth
Suppresses hypothalamic cyclicity and oestrous cycles
Suggests androgen exposure via hypothalamus determines ‘brain sex’