Male Testicular Function Flashcards
Spermatozoa / Sperm
- Contains genetic material in nucleus
- Contains mitochondria (energy)
- Contains flagellum (movement to deliver genetics)
Processes that don’t occur in spermatozoa
- No transcription - no new proteins synthesised
- No endoplasmic reticulum
- No cytoplasm so cytoplasmic reactions
Post-translational modifications in Sperm
- Glycosylation
- Phosphorylation
- Disulfide cross-linking, Ubiquitination, Acetylation + Methylation
Changes to proteins on cell membrane surface
Sperm’s journey after ejaculation
(1) Cervix –> (2) Uterus –> (3) Isthmus –> (4) Oviduct (fertilisation) –> (5) Oocyte (egg cell)
Swims ~18cm in 30-60 minutes
What is Spermatogenesis?
Biological process of producing mature sperm and occurs in the male gonad
How does spermatogenesis work?
- Begins as a basic eukaryote with typical organelles (with acrosomal vesicle on the nucleus )
- Centrioles move to either end of cell
- From the centrioles, microtubules form the centriole
- Excess cytoplasm is pinched off and lost from around the nucleus + the acrosome grows
A specialised sperm cell
A Sperm Cell’s Journey
From the epididymis to through the vans deferens and arrives at the ampulla
Glands in the male reproductive organs
Seminal vesicle
Prostate
Bulbourethral gland
Purpose of the scrotum
Provides cooler environment compared to the body (35-36 degrees)
- aids sperm’s development due to sensitivity to high temperatures
Where spermatogenesis occurs + sperm maturation
Coiled seminiferous tubule (SFT) in the testis
- Primary spermatocyte (diploid) goes through meiosis to form secondary haploid spermatocytes
- Spermatids then mature to become spermatozoa (spermiogenesis)
- Sertoli cell supports process by providing necessary nutrients
When is spermatogenesis initiated?
At puberty - caused by initiation of pulsatile release of gonadotropin releasing hormone (GnRH)
How long does spermatogenesis take?
74 days
How much sperm does a human produce?
1000 per heartbeat = 100-200 million/day
95% is abnormally formed so only a small proportion are capable of fertilising an egg
In between seminiferous tubules - Interstitial cells
Leydig cells - androgen (mainly testosterone) producing cell
Sertoli Cells - Tight junctions
- Tight junction with adjacent Sertoli cells maintain spermatogonial stem cell niche
Sertoli Cells - Blood testis barrier
- Separate developing germ cells from the immune system
- Provides a controlled chemical microenvironment for spermatogenesis
Sertoli cells - Adherens junction
Form intimate associations with germ cells (40-50)
What are Sertoli cells + what do they do?
Form a syncytium-like epithelial monolayer that germ cells are embedded
- Phagocytose cytoplasm of spermatozoa - spermiation
- Secrete fluid into lumen of SFT that lush spermatozoa into rete testis + epididymis post-differentiation
- Secrete Inhibin + Androgen Binding Proteins to regulate spermatogenesis
What are spermatogonia?
Reservoir of self-renewing stem cells (maintain germ cell line) and remain in the basement of the seminiferous tubule as
undifferentiated spermatogonia
- Some type ‘As’ S will form type ‘A’ S + start the process of spermatogenesis
Miotic Proliferation of Spermatogonia
Each type ‘A’ S goes through mitosis to form type ‘B’ S
- Will divide again to form primary spermatocytes that will go through meiosis
- Then move towards lumen + through blood-testis barrier
- Enters resting phase where chromosomes duplicate ready for meiosis
Meiotic Divisions of Sperm
I: Primary spermatocyte divide to form secondary spermatocyte (diff arrangement of genetic material)
II: Secondary spermatocytes divide to form haploid spermatid (diff sections of genetic material resulting in variation)
1 primary S => 4 round spermatids
Sperm developmemt
Spermatogonia (base) -> spermatocytes -> spermatids -> spermatozoa (lumen)
- Spermatocytes + spermatids move into adluminal compartment disrupting junctions between Sertoli cells
Spermiogenesis / Cytodifferentiation
Round spermatids elongate to form spermatozoa
Requires the formation of specialised sperm structures - acrosome, centriole, flagellum, mitochondria, nucleus
What is the acrosome?
- Formed from the golgi apparatus which migrates to one end of nucleus
- Contains hydrolytic enzymes which are released when sperm binds to the zona pellucida of the egg to aid penetration and thus fertillisation
- Found on the head of the cell + envelopes the nucleus
What is the Flagellum?
Formed from the centrioles when they migrate to opposite end of nucleus to acrosome + form axoneme
- For sperm movement through the female tract + penetration of the egg vestments
Mitochondria in sperm
- Helically arranged around first part of flagellum - midpiece
- Energy is needed for motility
Nucleus in Sperm
Sex determination of offspring (X or Y)
- Sperm DNA is highly condensed (histones replaced with protamines) to protect genome during transport
- DNA is transcriptionally and translationally inactive
Nuclear chromatin re-organisation in spermiogenesis
- Somatic histones are replaced by testis-specific histone variants
- Transition proteins incorporated in spermatid nuclei
- Protamines replace transition proteins in the late spermatids to pack genome into highly condensed sperm nucleus - no transcription factors can reach it
Cytoplasm in sperm
- Sperm had little cytoplasm (egg has a huge C which ends up in fetus)
- Excess C from spermiogenesis form residual body / cytoplasmic droplet which is phagocytosed by Sertoli cell
Developing sperm cells form a syncytium
During mitosis + meiosis, cytokinesis is incomplete
Syncytia persists until final stage of spermatogenesis
- Allows sharing of cytoplasmic components e.g. a Y sperm can supply essential proteins encoded by genes on X (axoneme + acrosome)
What is Spermiation?
Last step of spermatogenesis
- Facilitated by Sertoli cell cytoskeleton
- Cytoplasmic bridges rupture (syncytium)
- Spermatid cytoplasm is absorbed by Sertoli cell
- Sperm is released into lumen of seminiferous tubule in testis
Endocrine Control of Testicular Function - Hypothalamus-pituitary gonadal axis
Controlled by products released by testis somatic cells
- Within tubules - Sertoli cells
- Between tubules - Leydig cells
Extra-Testicular Regulation (Puberty) - Hypothalamus
Releases Gnhr (gonadotropin-releasing hormone) which act on the anterior pituitary
Extra-Testicular Regulation (Puberty) - Anterior Pituitary (Gonadotrophins) - LH (Luteinizing hormone)
- Binds to LH receptors on Leydig cells as well as Sertoli cells
- Induces Leydig cells to produce androgen (testosterone)
Extra-Testicular Regulation (Puberty) - Anterior Pituitary (Gonadotrophins) - FSH (follicle-stimulating hormone)
- Acts on testis (Sertoli cells) to maintain spermatogenesis
- Binds to FSH receptor on Sertoli cells
- Induce expression of androgen receptors on Sertoli cells to increase responsiveness to androgens
- Stimulates production of Androgen Binding Protein + Inhibin by Sertoli cells
Testicular Hormones’ Role - Androgen
- Development of testis of embryo
- Sexual function and characteristic (puberty)
- Reproductive function (adult)
- Produced by Leydig cells (between tubules)
- Negative feedback on hypothalamus + anterior pituitary by repressing LH + FSH production
Testicular Hormones’ Role - Androgen (mainly testosterone)
- Carried by ABP (androgen binding protein) in testicular fluid
- Converted to dihydrotestosterone (by 5alpha-reductase in Sertoli cells)
- Binds + affect Sertoli cells’ function
Testicular Hormones’ Role - Inhibin
Protein heterodimer hormone
- Produce by Sertoli cells
- Acts on pituitary gland
- Inhibit FSH production
Role of Testicular Product - Androgen Binding Protein (ABP)
- Product of Sertoli cells under testosterone stimulation
- Binds and carries testosterone in testicular fluid of seminiferous tubules
- Maintain high levels of testosterone 100x more conc. than blood ( T is lipid soluble so diffuse across membrane - binding prevents diffusion)
Movement of sperm into seminiferous tubules and rete testis
- Spermatozoa released from testis are immotile until they tranvers epididymis
- No cilia but fluid secretions from Sertoli cells + smooth muscle like cells in testicular tunic lamina propria of SFTs
- Periodic powerful contraction - peristalsis
Epididymal (male tract) Maturation - Anatomy
Regions:
- Caput - close testis - motility
- Corpus - fertilising ability
- Vas deferens - storage
Each segment
- Display different expression of genes]
- Maintains luminal ions concentrations
- Essential to regulate steps of sperm maturation
Epididymal Maturation
(sperm maturation during epididymal transit)
Sperm interact with epididymal epithelial cells – removal of the cytoplasmic droplet
- Retention of cytoplasmic droplets is associated with reduced fertility
Change sperm proteome – protein, lipid and sugar content
- Incorporated into the sperm cells
Change in sperm surface
- Removal and/or modification of external proteins, sugars and lipid sperm membrane
Intracellular signaling pathways activation during transit
- Addition or removal of protein phosphate groups - phosphorylation
Ejaculation
Sperm (2-5%) + Seminal plasm = semen
- Seminal plasma is secreted by accessory sex glands (seminal vesicles, prostate)
