L8: Male Reproductive Physiology Flashcards
What are the most important anatomical structures of testis?
- interstitium
- seminiferous tubules (highly coiled, site of sperm production)
- tunica albuginea
- rete testis (all the seminiferous tubules anastomose, join together)
- ductili efferentes
- vas deferens
- epididymis (separate from testis, but closely related)
What’s the function of tunica albuginea?
Thick layer of connective tissue, protective function
What are the two main functions of the testis? Where do they take place?
- spermatogenesis (in seminiferous tubules)
- steroidogenesis (in interstitium, Leydig cells)
Where does spermatogenesis take place?
Production of haploid germ cells takes place in seminiferous tubules
Where does steroidogenesis take place?
production of hormones takes place in interstitium (between seminiferous tubules), Leydig cells
Which way does germ cell maturation occur in males?
From the basal to luminal surface of the seminiferous epithelium
What are Sertoli cells? Where are they located?
Sertoli cells are the somatic supporting cells of spermatogenesis in the seminiferous epithelium
What are Sertoli cells? What is their function?
inside the epithelium, somatic supporting cells of spermatogenesis, very large cells
- structural
- protective
- secretory
- phagocytic
- stimulatory
- receive and transmit endocrine and paracrine signals
What is the structural function of Sertoli cells?
structural: scaffold for germ cells connected with adherens junctions, move germ cells basal –> apical
What is the protective function of Sertoli cells?
form blood testis barrier tight junctions between sertoli cells forms an immunologically privileged site – ensures that developing germ cells have undergone meiosis are not attacked by the host immune system
What is the secretory function of Sertoli cells?
secrete fluid to form seminiferous tubule lumen, secrete androgen binding protein to transport luminal androgens (fills the lumen)
What is the phagocytic function of Sertoli cells?
absorb waste organelles of developing germ cells
What is the stimulatory function of Sertoli cells?
gap junctions between SCs and sperm allow transfer of molecules
What is the receive and transmit endocrine and paracrine signals function of Sertoli cells?
eg they have receptors for FSH, testosterone whereas germ cells do not – germ cells do not have endocrine hormone receptors, all the receptors are on Sertoli cells
How many germ cells does one Sertoli cell support?
- Each Sertoli cell supports a fixed number of germ cells
- Number of Sertoli cells per testis is proportional to the daily sperm production
When do Sertoli cells stop dividing?
At puberty
What does interstitium consist of?
- Blood vessels,
- Leydig cells (androgen production)
- macrophages (phagocytosis)
- lymphatic cells (produces ECM),
- capillaries,
- fibrocytes (produces ECM))
What are the two main functions of interstitium?
- support spermatogenesis
- testosterone production
Where is testosterone produced? Which cells? Describe the pathway
Leydig cells are the site of testicular steroidogenesis
- Enzyme 3BHSD – important in testosterone production, can label Leydig cells
- Leydig cells are stimulated by LH
- Stimulation triggers cascade where from cholesterol testosterone is produced
- This testosterone is then converted to dihydrotestosterone (DHT) by 5alpha- reductase
What is the evidence that testosterone is needed for normal spermatogenesis?
- article showed that destruction of Leydig cells using EDS (ethane dimethane sulphonate) causes reduction in interstitial testosterone.
- 2 weeks after - reduction in testosterone causes gradual degeneration of spermatogenesis
- However after 2 weeks there is also regeneration of these Leydig cells observed
What is the function of Peritubular myoid cells? Where are they located?
PTM cells are smooth muscle cells, move sperm out of the testis and they surround seminiferous tubules.
What is the mechanism causing the contraction of PTM cells?
In sertoli cell: Big ET-1 is covnerted to ET-1 by ECE-1. ET-1 then activates Eta and Etb dimerised receptor on PTM cell, causing contraction.
Where does the sperm go after contraction of seminiferous tubules?
It brings sperm to the rete testis through the seminiferous tubule lumen and through efferent ducts
Where is epididymis found? What is the function of epididymis?
- Found within the scrotum
- concentrates sperm
- provides movement (tail)
- structural maturation (acrosome)
- storage
- Sperm taken straight from the testis are unable to fertilise in vivo
What is the evidence of epididymis importance?
Sperm taken straight from the testis are unable to fertilise an oocyte in vivo
How long is epidydimis?
Six meters long
How is epididymal pH important? What is the evidence?
Changes in epididymal pH can cause sperm tail malformations.
Evidence: Knockout of C-ros gene in mice causes underdevelopment of initial segment of epididymis. This results in a more alkaline epidydimal pH and defects in sperm tails and volume.
What is the function of epididymal stereocilia?
Help concentrate sperm
epithelial cells are tall columant; stereocilia, thought to increase surface area for absorption of testicular fluid (fluid is absorbed in epididymis)
Does epididymis require androgens for normal development?
Knock out: involution - shrinks, cells get really small
What is the function of vas deferens?
- straight muscular tube
- in humans, spermatozoa are stored in the vas prior to -ejaculation (in vas and in epididymis)
- it is thick layer of smooth muscle cells
- the thick muscular layers contract for peristalsis of sperm along the vas during ejaculation
How can vas deferens be manipulated as male contraception?
- vasectomy
- vasalgel injected in lumen, acts as a blocker for sperm, can be flushed from vas by an injection of sodium bicarbonate - fully reversible
What is congenital bilateral absence of vas deferens? What causes it?
- When vasa deferentia (plural) do not develop properly
- common in men with mutations in the cystic fibrosis transmembrane regulator (CFTR) gene
- some men with mutations in CFTR have full CF, but in others CBAVD is their only symptom
Which parts produce seminal plasma?
- prostate gland
- seminal vesicle
What does seminal plasma consist of? What’s the percentage? What’s the function of each component?
- nutrients (fructose, proteins)
- alkaline solution (needed for survival)
- lubricant (helps sperm swim)
What is the function of seminal vesicles?
- seminal vesicle fluid makes up 70-85% seminal fluid
- composes the second part of the ejaculate
- contains fructose: provides sperm with energy
What promotes semen coagulation at ejaculation?
Promoted by semenogelin I and II, expressed exclusively in the seminal vesicles
Why do rodents need large seminal vesicles?
Large seminal vesicles needed in species where males leave a copulatory plug, to stop another male sperm from getting in
What is the function of prostate?
Produces prostatic fluid which mixes with sperm to make up the first part of the ejaculate.
What’s the pH of prostatic fluid? How is that important?
Alkaline: helps sperm survive in the acidic female reproductive tract, contains Zn2+
What is benign prostatic hyperplasia?
- non-cancerous enlargment of the prostate due to cell multiplication
- 90% of men around the age of 80 have BPH
Where is prostate-specific antigen produced?
PSA a.k.a kallikrein 3 (Klk3) is produced by prostate epithelial cells
What is the function of PSA?
PSA cleaves semenogelins to liquify coagulated semen in the female reproductive tract: allows sperm to swim freely (liquifies in a few minutes in female)
When can levels of PSA increase?
Levels may increase with prostate cancer/BPH, can be used as a diagnostic test
Which structure in penis causes erection?
Corpus cavernosum - spongy structure, erection when filled with blood
What is the mechanism of erection?
Nitric oxide acts on guanylate cyclase, which converts GTP to cGMP, the more cGMP the more relaxation of smooth muscle, the more blood flows to the penis
How does viagra work?
cGMP is reduced by PDE-5, viagra acts as PDE-5 inhibitor, causing more erection
What is the mechanism of semen coagulation and liquification?
- PSA and Zinc (inhibits PSA) released from prostate
- sperm released from epididymis
- semenogelin released from seminal vesicles
upon ejaculation all of these mixed up, zinc preferably binds to semenogelins, causes crosslinking (coagulation)
15-60 min after in the cervix, PSA is activated when zinc is bound by semenogelin, causing liquification.
