Male Testicular Function

Question 1

Spermatozoa / Sperm

Answer 1

• Contains genetic material in nucleus
• Contains mitochondria (energy)
• Contains flagellum (movement to deliver genetics)

Question 2

Processes that don’t occur in spermatozoa

Answer 2

• No transcription - no new proteins synthesised
• No endoplasmic reticulum
• No cytoplasm so cytoplasmic reactions

Question 3

Post-translational modifications in Sperm

Answer 3

• Glycosylation
• Phosphorylation
• Disulfide cross-linking, Ubiquitination, Acetylation + Methylation

Changes to proteins on cell membrane surface

Question 4

Sperm’s journey after ejaculation

Answer 4

(1) Cervix –> (2) Uterus –> (3) Isthmus –> (4) Oviduct (fertilisation) –> (5) Oocyte (egg cell)

Swims ~18cm in 30-60 minutes

Question 5

What is Spermatogenesis?

Answer 5

Biological process of producing mature sperm and occurs in the male gonad

Question 6

How does spermatogenesis work?

Answer 6

1. Begins as a basic eukaryote with typical organelles (with acrosomal vesicle on the nucleus )
2. Centrioles move to either end of cell
3. From the centrioles, microtubules form the centriole
4. Excess cytoplasm is pinched off and lost from around the nucleus + the acrosome grows

A specialised sperm cell

Question 7

A Sperm Cell’s Journey

Answer 7

From the epididymis to through the vans deferens and arrives at the ampulla

Question 8

Glands in the male reproductive organs

Answer 8

Seminal vesicle
Prostate
Bulbourethral gland

Question 9

Purpose of the scrotum

Answer 9

Provides cooler environment compared to the body (35-36 degrees)
- aids sperm’s development due to sensitivity to high temperatures

Question 10

Where spermatogenesis occurs + sperm maturation

Answer 10

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

Question 11

When is spermatogenesis initiated?

Answer 11

At puberty - caused by initiation of pulsatile release of gonadotropin releasing hormone (GnRH)

Question 12

How long does spermatogenesis take?

Answer 12

74 days

Question 13

How much sperm does a human produce?

Answer 13

1000 per heartbeat = 100-200 million/day

95% is abnormally formed so only a small proportion are capable of fertilising an egg

Question 14

In between seminiferous tubules - Interstitial cells

Answer 14

Leydig cells - androgen (mainly testosterone) producing cell

Question 15

Sertoli Cells - Tight junctions

Answer 15

• Tight junction with adjacent Sertoli cells maintain spermatogonial stem cell niche

Question 16

Sertoli Cells - Blood testis barrier

Answer 16

• Separate developing germ cells from the immune system
• Provides a controlled chemical microenvironment for spermatogenesis

Question 17

Sertoli cells - Adherens junction

Answer 17

Form intimate associations with germ cells (40-50)

Question 18

What are Sertoli cells + what do they do?

Answer 18

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

Question 19

What are spermatogonia?

Answer 19

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

Question 20

Miotic Proliferation of Spermatogonia

Answer 20

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

Question 21

Meiotic Divisions of Sperm

Answer 21

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

Question 22

Sperm developmemt

Answer 22

Spermatogonia (base) -> spermatocytes -> spermatids -> spermatozoa (lumen)

• Spermatocytes + spermatids move into adluminal compartment disrupting junctions between Sertoli cells

Question 23

Spermiogenesis / Cytodifferentiation

Answer 23

Round spermatids elongate to form spermatozoa
Requires the formation of specialised sperm structures - acrosome, centriole, flagellum, mitochondria, nucleus

Question 24

What is the acrosome?

Answer 24

• 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

Question 25

What is the Flagellum?

Answer 25

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

Question 26

Mitochondria in sperm

Answer 26

• Helically arranged around first part of flagellum - midpiece
• Energy is needed for motility

Question 27

Nucleus in Sperm

Answer 27

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

Question 27

Nuclear chromatin re-organisation in spermiogenesis

Answer 27

• 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

Question 28

Cytoplasm in sperm

Answer 28

• 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

Question 29

Developing sperm cells form a syncytium

Answer 29

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)

Question 30

What is Spermiation?

Answer 30

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

Question 31

Endocrine Control of Testicular Function - Hypothalamus-pituitary gonadal axis

Answer 31

Controlled by products released by testis somatic cells
- Within tubules - Sertoli cells
- Between tubules - Leydig cells

Question 32

Extra-Testicular Regulation (Puberty) - Hypothalamus

Answer 32

Releases Gnhr (gonadotropin-releasing hormone) which act on the anterior pituitary

Question 32

Extra-Testicular Regulation (Puberty) - Anterior Pituitary (Gonadotrophins) - LH (Luteinizing hormone)

Answer 32

• Binds to LH receptors on Leydig cells as well as Sertoli cells
• Induces Leydig cells to produce androgen (testosterone)

Question 32

Extra-Testicular Regulation (Puberty) - Anterior Pituitary (Gonadotrophins) - FSH (follicle-stimulating hormone)

Answer 32

• 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

Question 32

Testicular Hormones’ Role - Androgen

Answer 32

• 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

Question 33

Testicular Hormones’ Role - Androgen (mainly testosterone)

Answer 33

• Carried by ABP (androgen binding protein) in testicular fluid
• Converted to dihydrotestosterone (by 5alpha-reductase in Sertoli cells)
• Binds + affect Sertoli cells’ function

Question 34

Testicular Hormones’ Role - Inhibin

Answer 34

Protein heterodimer hormone
- Produce by Sertoli cells
- Acts on pituitary gland
- Inhibit FSH production

Question 35

Role of Testicular Product - Androgen Binding Protein (ABP)

Answer 35

• 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)

Question 36

Movement of sperm into seminiferous tubules and rete testis

Answer 36

• 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

Question 37

Epididymal (male tract) Maturation - Anatomy

Answer 37

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

Question 38

Epididymal Maturation
(sperm maturation during epididymal transit)

Answer 38

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

Question 39

Ejaculation

Answer 39

Sperm (2-5%) + Seminal plasm = semen
- Seminal plasma is secreted by accessory sex glands (seminal vesicles, prostate)