10. Testicular Function

Question 1

Formation of the male reproductive system

Answer 1

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

Question 2

Spermatogenesis

Answer 2

Sperms are highly specialised complex cells, produced in large numbers
In human males 100 million per day
3 phases: proliferation, dilation, and differentiation

Question 3

Spermatogenesis proliferation stage

Answer 3

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

Question 4

Spermatogenesis division phase

Answer 4

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

Question 5

Spermatogenesis differentiation

Answer 5

Round spermatids elongate to form elongated spermatids and finally mature spermatozoa
Formation of specialised sperm structure: acrosome, Flagellum, centrioles, mitochondria, nucleus, cytoplasm

Question 6

Acrosome

Answer 6

Formed from Golgi apparatus
Contains hydrolytic enzymes and released upon binding to Zona pellucida
Receptor for fusion

Question 7

Nucleus

Answer 7

Sex determination

Sperm DNA become highly condense - hair ones replaced by protamines

Question 8

Cytoplasm

Answer 8

Superfluous cytoplasm form residual body (cytoplasmic droplet) which is phagocytosed by Sertolli cells

Question 9

Spermiation

Answer 9

Cells released into lumen

Question 10

Mitotic proliferation

Answer 10

Number of mitotic divisions is species specific and will determine number of sperm produced
Each A spermatogonium undergoes mitosis to form type B spermatocytes

Question 11

Blood testis development

Answer 11

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

Question 12

Post pubertal testis

Answer 12

Within and between seminiferous tubules 2 compartments
Sertolli cells sperm develop
Leydig cells

Question 13

Flagellum

Answer 13

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

Question 14

Kinetics of spermatogenesis

Answer 14

Human - whole process takes 64 days
Duration is specific
Controlled by germ cells
Continuous not periodic release

Question 15

Mitochondria

Answer 15

Energy for motility - helically arranged around first part of flagellum

Question 16

Products

Answer 16

Cytokines - inhibin, AMH
Oestrogens - small amount in human males -> sperm maturation
Androgens - mainly testosterone embryonic development of reproductive system, reproductive function, sexual function

Question 17

Puberty

Answer 17

Hypothalamus begins to secrete gonadotrophin releasing hormone (GnRH)
GnRH induces the anterior pituitary to produce LH and FSH

Question 18

Androgens

Answer 18

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

Question 19

Epididymis

Answer 19

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

Question 20

Ejaculation

Answer 20

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

Question 21

Seminal vesicles

Answer 21

Rich in fructose
Fibrinogen like substrate and coagulating enzyme from prostate - ejaculate clotting
Provides majority of ejaculate volume
Sac like glands empty upon ejaculation

Question 22

Feedback loops

Answer 22

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

Question 23

Sperm maturation and transport

Answer 23

~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

Question 24

Sperm maturation and transport - Vas deferens

Answer 24

Storage reservoir
Densely packed with little fluid
Sperm stored in cauda epididymis for a few days before moving to Vas deferens

Question 25

Capacitation

Answer 25

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

Question 26

Prostate

Answer 26

Solid tissue mass - secreted during copulation
Alkaline secretions high in zinc important in ejaculation function
Enzyme for ejaculate clotting and liquefaction

Question 27

Bulbourethral gland

Answer 27

Lubrication
Preejaculate
Neutralisation

Question 28

Testis development

Answer 28

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