10. Testicular Function Flashcards
Formation of the male reproductive system
SRY - sex determining region Y gene, testis determining factor, encode DNA binding protein: TF. Triggers off cascade of gene expressions for testes development
PGCs appear around week 3 in epithelium of yolk sac
Primordial germ cells gives rise to the gametes - weeks 3-7 proliferate by mitosis. Migrate by amoeboid movement to region of dorsal wall that will form the Gonads
Development is indifferent until week 7
Conserved across mammals
Female mice with SRY transgene show make development
Spermatogenesis
Sperms are highly specialised complex cells, produced in large numbers
In human males 100 million per day
3 phases: proliferation, dilation, and differentiation
Spermatogenesis proliferation stage
At puberty, prospermatogenesis are reactivated and and undergo mitosis in basal compartment of tubule as spermatogonia (spermatogonial stem cells = reservoir of self renewing stem cells)
Forms a spermatogonia = start of spermatogenesis
Spermatogenesis division phase
Primary spermatocytes move into columnial compartment passing through BTB
Undergo first meiotic division, forms 2 secondary spermatocytes
Second meiotic division to form haploid round spermatids
Spermatogenesis differentiation
Round spermatids elongate to form elongated spermatids and finally mature spermatozoa
Formation of specialised sperm structure: acrosome, Flagellum, centrioles, mitochondria, nucleus, cytoplasm
Acrosome
Formed from Golgi apparatus
Contains hydrolytic enzymes and released upon binding to Zona pellucida
Receptor for fusion
Nucleus
Sex determination
Sperm DNA become highly condense - hair ones replaced by protamines
Cytoplasm
Superfluous cytoplasm form residual body (cytoplasmic droplet) which is phagocytosed by Sertolli cells
Spermiation
Cells released into lumen
Mitotic proliferation
Number of mitotic divisions is species specific and will determine number of sperm produced
Each A spermatogonium undergoes mitosis to form type B spermatocytes
Blood testis development
Develops during puberty prior to onset of spermatogenesis
Between basal and ad luminal compartment of seminiferous tubule
Adheren/gap/tight junctions
Two functions: 1. Separate spermatids from immune system preventing immune response
2. Selective transport of ions and small molecule
Post pubertal testis
Within and between seminiferous tubules 2 compartments
Sertolli cells sperm develop
Leydig cells
Flagellum
For sperm movement through the female tract and penetration of the egg vestments
Centrioles migrate to opposite end of nucleus to acrosome
Distal centriole forms axoneme of flagellum
Proximal sperm centriole forms the spindle for the first mitotic division of the embryo
Kinetics of spermatogenesis
Human - whole process takes 64 days
Duration is specific
Controlled by germ cells
Continuous not periodic release
Mitochondria
Energy for motility - helically arranged around first part of flagellum
Products
Cytokines - inhibin, AMH
Oestrogens - small amount in human males -> sperm maturation
Androgens - mainly testosterone embryonic development of reproductive system, reproductive function, sexual function
Puberty
Hypothalamus begins to secrete gonadotrophin releasing hormone (GnRH)
GnRH induces the anterior pituitary to produce LH and FSH
Androgens
Produced by Leydig cells
Blood lymph seminiferous tubules
Converted to dihydrotesterone (more active) by Sertolli cells (5 alpha reductase)
Some binds to androgen receptors in Sertoli cells - inhibin produced, depresses FSH production by anterior pituitary gland; AMH Sertoli cells embryonic role in development of reproductive system
Some binds to ABP - LH binds to LHR on Leydig cells and induces them to produce testosterone which moves to the tubules and binds to the androgen receptor on Sertoli cells (>300 genes) induces expression of androgen receptor. Also stimulates production of ABP and inhibin
Epididymis
Sperms are washed from Sertoli cells through rete testis to epididymis
Most of the fluid is reabsorbed - oestrogen
Sperm passage tubes 10-14 days sperm maturation
Plays active role - provides many molecules necessary for sperm to acquire fertilising ability and motility - androgen dependent
Ejaculation
Sperm and seminal plasma = semen
Approx 3ml in humans
Seminal phase - transport nutrition buffering, antioxidants; secreted by the accessory sex glands (seminal vesicles prostate); alkaline fluid to protect sperm from acidic conditions of the vagina
Seminal vesicles
Rich in fructose
Fibrinogen like substrate and coagulating enzyme from prostate - ejaculate clotting
Provides majority of ejaculate volume
Sac like glands empty upon ejaculation
Feedback loops
GnRH ->FSH/LH -> 2nd messenger/Leydig cells
Second messenger -> Cell products (spermatocytes, spermatogonium) -> ABP -> ABP-T
Leydig cells -> testosterone -> Sertoli cells/to body for second effect
Testosterone negative feedback to FSH/LH and GnRH
Cel products -> inhibin negative feedback FSH/LH
Sperm maturation and transport
~1 million make it to the environs of the oocyte
Spermatozoa leave the testis immobile and unable to recognise or bind an egg - need to undergo maturation in the male tract and capacitation in female tract
Sperm maturation and transport - Vas deferens
Storage reservoir
Densely packed with little fluid
Sperm stored in cauda epididymis for a few days before moving to Vas deferens
Capacitation
Happens in female tract, not well understood
Sperm must undergo some form of physiological change or capacitation before it is capable of penetrating the egg
Prostate
Solid tissue mass - secreted during copulation
Alkaline secretions high in zinc important in ejaculation function
Enzyme for ejaculate clotting and liquefaction
Bulbourethral gland
Lubrication
Preejaculate
Neutralisation
Testis development
From week 7
1. Column of cells from coelamic epithelium - proliferate and penetrate deep into the medullary mesenchyme - primitive sex cords: express SRY
2. PGCs
3. Migratory cells from mesonephric primodia-vasculature Leydig myeloid cells
SRY no longer expressed testes direct further development of male reproductive system (androgens/antiMullerian hormone AMH)
Between seminiferous tubules - vascularisation and clusters of Leydig cells form
Within seminiferous tubes: prospermatogonia, mesodermal cord cells, inhibition of meiosis
