Sex: Development and Gametes Flashcards
What are primordial germ cells and how do they allow for gonadal development?
- Arise at the base of the allantois and migrate to genital ridges
- Develop into either testes or ovaries (sry gene causes differentiation to male)
- Differentiate into either supporting cells, steroidogenic cells or germ cells.
Name the 4 genes involved in sex determination in an embryo
Sry - On Y chromosomes
Sox9 - maintains Sertoli cells; activates MIH
Dax1 - inhibits sox9/MIH
MIH - removes Mullerian duct
Sf1
Wt4
Give examples of how male sex is determined across species:
Active induction by sry gene (mammals):
- Male development active; female passive
Dose dependent on male gene:
- Birds (M = ZZ; F = ZW) where higher dose of Dmrt1 gene on Z in males induces development.
Temperature determined:
- Reptiles have no sex chromosomes
- Turtles (>32˚ C = female <28˚ C = male) due to temperature sensitive aromatase affecting testosterone/oestrogen balance
Explain some chromosomal disorders in humans:
Turner’s syndrome:
- XO producing infertile female (crossing over inhibited)
Klinefelter’s syndrome:
- XXY producing infertile male
- Slightly feminine physique and breast tissue
Guevedoces ‘penis at twelve’:
- XY but appear female until second surge of testosterone at puberty
- Due to alpha-reductase deficiency (testosterone not converted to dihydrotestosterone)
What is the evidence for bi-potential gonadal sex early in embryonic development?
- Initially both the Wolffian duct (male) and mullerian duct (female) form.
- Castrated male ends up with both ducts (even with androgens)
- Mullerian duct disappears only if MIH present (male MIH knockout results in both ducts maintained).
How is the Wolffian duct selected for in males?
- Sertoli cells secrete and respond to sry gene (+ve feedback)
- Activates MIH causes degradation of mullerian duct.
- Wolffian duct kep due to androgens and leydig cells
Which genes and molecules are involved in selecting for the wolffian duct in males?
- Sry suppresses dax1 expression (so dax1 inhibits sox9 less)
- Sox9 maintains sertoli cells and activates mullerian inhibiting hormone (MIH)
- Causes atrophy of mullerian duct
- Wolffian duct kept due to leydig cells and androgens
Why do females only have a mullerian duct?
Female development passive:
- Dax1 active which inhibits sox9 activity
- Suppresses androgen production (e.g. wnt4)
- Wolffian duct dissipates by neglect
- Mullerian ducts become fallopian tubes
What are the different ways that sex can be identified?
- Chromosomal sex
- Brain sex (behaviour and ovulation)
- Phenotypic sex
- Gonadal sex
Give experimental evidence for brain masculinisation:
Androgens converted to oestrogen in brain (by aromatase) to have effect in male:
- Prevents ovaries from undergoing cyclic ovulation
- Male with removed testes and inserted ovaries will have ovarian cycles if changed at birth but not if done later.
What are the functions of Sertoli cells (during development and reproduction)?
What about leydig cells?
Sertoli cells
During development:
- Sexual differentiation (secrete sry)
- Create blood/testes barrier
For spermatogenesis:
- Mechanical and nutritional support
- Contain androgen binding protein for HPG axis
Leydig cells
- Produce testosterone
Describe the stages of spermatogenesis:
- A0 spermatogonia self-renew and divide by mitosis
- Become spermatocytes (4n = large cells) and undergo mitosis
- Haploid spermatids formed
- Spermiogenesis occurs
- Acrosome, flagella and mitochondrial sheath formed
- Residual cytoplasm removed
- Histones replaced by protamines - Mature spermatozoa formed
How is sperm production kept continuous?
- Renewal of A0 spermatogonia (every 64 days)
Spermatogenic cycle:
- Re-initiated after 1/4 of total time (e.g. after 16 days in humans)
Spermatogenic wave:
- Progressive changing of cell associations to a particular spermatogenic cycle
Reduce damage to sperm:
- Temperature controlled
- Counter current exchange
- External
- Extra sweat glands
How does the HPG axis stimulate sperm production?
GnRH stimulates gonadotrophs in pituitary to produce FSH and LH:
- LH stimulates testosterone production (binds LHR on Leydig). Therefore regulates initiation of spermatogenesis.
- FSH acts on Sertoli cells
Negative feedback loops:
- Testosterone produced by Leydig cells inhibits GnRH and LH/FSH production
- Inhibin from Sertoli cells inhibits FSH secretion from pituitary
How does FSH stimulate Sertoli cells?
- Increased protein synthesis
- Upregulates testosterone receptor expression and testicular fluid
- Increases inhibin secretion
What changes do sperm undergo through the epididymis?
Passive travel through (using smooth muscle and cilia).
Increased fertilisation capability:
- Structural changes (removal of cytoplasmic droplet and head sculpting)
- Glycoprotein coat formed of EPPIN (peptidase inhibitor) and lipocalins (prevents premature acrosome release)
What are the properties and contents of seminal fluid?
- pH 7.2-7.8 (combat acidic uterus)
- Salts and ions
- Coagulating enzymes; proteolytic enzymes; mucus
- Roughly 280million sperm per ejaculate (only 200 make it to oocyte)
How do erection and ejaculation occur? how does Viagra help?
Parasympathetic control:
- ACh release causing cGMP synthesis, NO synthesis and smooth muscle relaxation
- Increased blood flow to sinuses (corpus cavernosa and spongiosum)
- Viagra: inhibits PDE type 5, maintaining cGMP levels
Ejaculation: sympathetic control:
- Smooth muscle contraction in vans deferens and accessory gland