Endocrinology of Male Repro and Infertility - Huleihal

Question 1

Where is the majority of seminal fluid produced?

Answer 1

Seminal vesicles: 2/3 of volume

most of rest by prostate but also a bit from bublo-urethral/Cowper’s gland, and Littre’s gland (and less from ampulla, vas deferens and testis)

Question 2

What are the components of seminal fluid?

Answer 2

Plasma:

Water

Fructose (from seminal vesicles)

Fibrinogen (clots semen)

Fibrinolytic enzymes (from prostate)

Prostaglandins (to suppress vaginal immune cells, from seminal vesicles)

Buffers (bulbourethral)

Cells:

mature sperm cells, immature sperm cells, epithelial cells and leukocytes (4%- supressor T cells to diminish vaginal immune response)
More monocytes and macrophages (20-30%) and granulocytes (50-60%)- to defend against harsh vaginal conditions nonspecifically

Question 3

What is the pathway of sperm from spermatogenesis in the seminiferous tubules to motility and fertility?

Answer 3

From seminiferous tubules within lobules
to rete testis
to efferent ductules
to head of epididymis where they begin to gain fertilization and motility abilities. By the tail of the epididymis they are fertile and motile.

Then to vas deferens.

Question 4

What cells/tissues comprise the seminiferous tubules and interstitium?

Answer 4

Seminiferous tubule:
Basement membrane part (with peritubular cells outside) and luminal part
Spermatogonium stem cells closest to the BM which can proliferate and differentiate
Sertoli and lumen cells have different composition, sertoli cells communicate with other surrounding cells
Tight junctions between sertoli cells prevent immune cells from attacking spermatogonium-derived cells (primary spermatocytes) and high MW proteins (antibodies) from entering but allow nutrients to enter. If exposed to high levels of cytokines from inflammation they will be opened and infertility will result.
Microenvironment is niche of the spermatogonium
Gap junctions/cytoplasmic bridges between groups of spermatogonia synchronize them during development

Interstitium:
Fibroblasts, blood vessels, lymph vessels, Leydig cells (associated with peritubular cells)
High concentration of macrophages (20-30%: produce growth factors)

Question 5

What cells regulate spermatogonia directly vs. indirectly?

Answer 5

Sertoli cells and peritubular directly regulate spermatogonium differentiation/proliferation

Leydig cells regulate through production of testosterone

Question 6

What is the difference between spermatogenesis and spermeation

Answer 6

Spermatogenesis is the development of long spermatozoa from round spermatids

Spermeation is the expulsion of spermatozoa from in between Sertoli cells into the lumen of the seminiferous tubule

Question 7

Describe spermiogenesis

Answer 7

In epididymis

1. Acrosome forms at the head
2. Microtubules form near the tail (at midpiece) and mitochondria form around them.
3. Flagellum grows from microtubules in a 9+2 pattern- axoneme
4. Cytoplasm phagocytosed by sertoli cells as sperm elongates
5. Sperm swims out of the epididymis

Question 8

How is spermatogensis regulated by hormones?

Answer 8

1. Hypothalamus releaases GnRH into anterior pituitary
2. Anterior pituitary releases FSH and LH
3. FSH acts on Sertoli cells and LH on Leydig cells
4. Sertoli cells stimulate spermatogenesis and induces Sertoli cells to produce ABP, transferrin, inhibin (to inhibit FSH) and estradiol.
5. Leydig cells stimulate testosterone production in the testes which acts on organs in itself and inhibits LH in the anterior pituitary and GnRH production by the hypothalamus and regulates ABP production by Sertoli cells.
   They contain cytosolic receptor for testosterone which also bind dehydrotestosterone and progesterone.
   Negative feedback by estrogen.
   LH/testosterone affect differentiation of spermatocyte from primary to secondary.
6. Testosterone and FSH produce ABP synergistically on Sertoli cells.

No receptors on spermatogonia, all effects through Sertoli cells

Question 9

What is the time span of spermatogenesis?

Answer 9

74 days in the testes

1-2 weeks in epididymis

3 months total to be produced

Question 10

What are possible causes of male infertility?

Answer 10

1. Endocrine Factors
2. Testicular Factors
   Cryptorchidism-undescended
   Testicular torsion or trauma
   Varicocםele (no venous drainage-excess fluid)
   Infection
   Higher temperature
3. Environmental factors
   Gonadotoxins
   Anabolic steroids
   Meds: sulfasalozine, cyclosporins, colchasine
4. Idiopathic

Question 11

What are the methods of functional sperm assays

Answer 11

1. Semen analysis (sperm parameters)
   Can have problems in morphology, adhesion/attachment, penetration capacity
   If more eosin-positive cells >10% means dead cells
2. Sperm-Cervical mucus interaction (ability of sperm to reach uterine cavity)
3. Hemizona assay (binding to zona pellucida)
4. Sperm penetration assay (fusion with oolemma)