7.7B. Male reproductive physiology Flashcards by Aurora H

I. Basics
1. What are the main features of MALE REPRODUCTIVE PHYSIOLOGY?

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I. Basics
2. Describe anatomy of male reproductive system

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I. Basics
3A. What are the 2 main compartments of testicular lobule?

Intratubular compartment
Peritubular compartment

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I. Basics
3C. What are the features of Peritubular compartment?

Neurovascular elements
CT
Immune cells
Interstitial cells of Leydig (testosterone production)

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I. Basics
3B. What are the features of Intratubular compartment?

Seminiferous epithelium is composed of:
- Sperm cells (in different phases of spermatogenesis)
- Sertolli cells – responsible for ‘’nursing’’ + maintenance of
developing sperm cells

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II. Spermatogenesis
1. What are the requirements for Spermatogenesis?

The process from spermatogonium to fully developed sperm cells
- Takes ~72 days, spend ~50 days in the testis
- Vitamin A is essential

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II. Spermatogenesis
2. What are the 4 steps of spermatogenesis?

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II. Spermatogenesis
3. What will Spermatogonia undergo?

permatogonia will undergo mitosis to replicate themselves to make more spermatogonia (will remain at basal lamina), or become primary spermatocytes

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II. Spermatogenesis
4. What will Primary spermatocytes undergo?

Primary spermatocytes (diploid 4N DNA) will undergo meiosis 1 (chromosomal duplication, synapsis, crossing over, homologous recombination)
=> to form 2 secondary spermatocytes (they get closer to the lumen of tubule)

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II. Spermatogenesis
5. What will Secondary spermatocytes undergo?

The 2 secondary spermatocytes (haploid 2N DNA) carry out meiosis 2 to result in the formation of 4 haploid spermatids

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II. Spermatogenesis
6. What will Spermatids undergo?

Spermatids remain interconnected with cytoplasmic bridges that provide the development and differentiation of these cells
=> Spermatids will move through the seminiferous tubules, until they reach the head of epididymis, where they are still not mature!

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III. Spermiogenesis
1. What is Spermiogenesis

Spermiogenesis: maturation of the spermatozoa
- Size of the nucleus decreases
- Tail formation
- Acrosome development: contains protease enzymes + other mediators that are
essential for the insemination of the X-cell

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III. Spermiogenesis
2. What happen in Spermiogenesis?

Size of the nucleus decreases
Tail formation
Acrosome development: contains protease enzymes + other mediators that are essential for the insemination of the X-cell

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III. Spermiogenesis
3. What happen in acrosome development?

Contains protease enzymes other mediators that are essential for the insemination of the X-cell

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IV. What is Spermiation?

The completely developed sperm cell will leave the seminiferous epithelium and is released into the lumen of the seminiferous tubules

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V. Sertoli cells
1. What are Sertoli cells?

Epithelial cells that line the seminiferous tubules
=> nurse developing sperm cells

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V. Sertoli cells
2A. How do Sertoli cells keep communicate with other cells? (IMPORTANT)

They maintain adherens + gap junctions with developing sperm cells
Tight junctions with adjacent Sertoli cells, which create 2 sub-compartments: basal and apical apartment

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V. Sertoli cells
2B. How do Sertoli cells maintain adherens + gap junctions with developing sperm cells?

Guide developing sperm cells from the basal lamina to the lumen of seminiferous tubules
Breakdown of these connections will lead to spermiation

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V. Sertoli cells
2C. Tight junctions with adjacent Sertoli cells, which create 2 sub-compartments: Apical and basal compartments
=> What are the characteristics of basal compartment?

Contains spermatogonia + early primary spermatocytes

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V. Sertoli cells
2D. Tight junctions with adjacent Sertoli cells, which create 2 sub-compartments: Apical and basal compartments
=> What are the characteristics of Adluminal/apical compartment?

This compartment contains late primary spermatocyte and all later forms

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V. Sertoli cells
3. What is the role of the Blood-testis-barrier (BTB)?

Blood-testis-barrier (BTB): Creates a specialized
immunologically safe microenvironment for developing sperm

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V. Sertoli cells
4. What are the features of Blood-testis-barrier (BTB)?

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V. Sertoli cells
5A. What are the 5 main functions of Sertoli cells?

(GFs, fluid production, phagocytosis of residual bodies)
1. Receptor expression
2. CYP19 (aromatase) expression
3. Androgen binding protein (ABP)
4. Endocrine functions
5. Cell-cell interactions

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V. Sertoli cells
5B. One of the main functions of Sertoli cells is
“RECEPTOR EXPRESSION”
=> Explain

Androgen receptor (responds to testosterone)
FSH receptor (binds FSH + stimulates Sertoli cell function)
These hormones regulate spermatogenesis indirectly

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V. Sertoli cells 5C. One of the main functions of Sertoli cells is "CYP19 (aromatase) expression:" => Explain

- Conversion of testosterone to estradiol - Estradiol important in spermatogenesis, because developing sperm cells express estradiol receptors

V. Sertoli cells 5D. One of the main functions of Sertoli cells is "Androgen binding protein (ABP)" => Explain

Binds testosterone in the lumen of seminiferous tubules => maintains high intraluminal [testosterone], which is essential for maintenance of spermatogenesis

V. Sertoli cells 5E. One of the main functions of Sertoli cells is "Endocrine functions" => Explain

1. Anti-müllerian hormone (AMH) will during development induce regression of the Müllerian duct (female reprod.tract) => is maintained throughout life 2. Inhibin (heterodimer protein) belongs to the TFG-β family => responsible for regulation of testosterone production

V. Sertoli cells 5E. One of the main functions of Sertoli cells is "Cell-cell interactions" => Explain

ICAM (intracellular adhesion molecule) is important in binding of sperm cells to the Sertoli cells during their maturation

VI. Leydig cells 1. Which compartment can you find Leydig cells?

peritubular compartment

VI. Leydig cells 2. What are the features of Leydig cells?

VII. Androgen production in the testes 1. How is androgen produced in the testes?

- Free cholesterol is transferred into the mitochondrial matrix in a steroidogenic acute regulatory (StAR) protein dependent manner. - Androgen production in the Leydig cells

VII. Androgen production in the testes 2. Make a schematic diagram of Androgen production in the testes

VII. Androgen production in the testes - Intratesticular androgen 3A. Explain the fate of Intratesticular androgen

VII. Androgen production in the testes - Intratesticular androgen 3B. What is the role of Aromatase?

Aromatase converts testosterone into estradiol

VII. Androgen production in the testes - Intratesticular androgen 3C. What are the receptors for Leydig cells and Sertoli cells?

- Leydig cells have LH receptors, while Sertoli cells have FSH receptors (both Gs) => both will lead to new protein synthesis

VII. Androgen production in the testes - Extratesticular androgen 4. What does Extratesticular androgen mean?

testosterone that leaves the testis

VII. Androgen production in the testes - Extratesticular androgen 5. How are androgens transported?

Androgens are transported in the (peripheral) circulatory system with the help of sex hormone binding globulin (SHBG)

VII. Androgen production in the testes - Extratesticular androgen 6. What is the fate of testosterone in adipose tissue?

Adipose tissue: testosterone is converted into estradiol-17β by aromatase (CYP19)

VII. Androgen production in the testes - Extratesticular androgen 6A. What is the fate of testosterone in Genital skin + prostate?

Genital skin + prostate: testosterone is converted into dihydrotestosterone (DHT) by 5α-reductase

VII. Androgen production in the testes - Extratesticular androgen 6B. What are the features of dihydrotestosterone (DHT)?

1. Has much higher affinity for binding to androgen receptors 2. The most active form of androgens that can be found is DHT

VII. Androgen production in the testes - Transport and metabolism of testosterone 7A. How is testosterone transported in the circulation?

Adipose tissue: testosterone is converted into estradiol-17β by aromatase (CYP19)

VII. Androgen production in the testes - Transport and metabolism of testosterone 7B. What is the % of albumin-bound testosterone?

- Albumin-bound = 50% (low affinity for testosterone, but albumin is abundant in blood)

VII. Androgen production in the testes - Transport and metabolism of testosterone 7C. What is the % of SHBG-bound testosterone?

- SHBG-bound = 45% (high affinity for testosterone, but SHBG is scarce in blood)

VII. Androgen production in the testes - Transport and metabolism of testosterone 7D. What is the % of CBG-bound testosterone?

- CBG-bound (corticosteroid-binding-globulin) = 4%

VII. Androgen production in the testes - Transport and metabolism of testosterone 7E. What is the % of free testosterone? What is its fate?

- Free testosterone = 1-3% => can be converted into estradiol (aromatase-CYP19) and DHT (5α-reductase)

VII. Androgen production in the testes - Transport and metabolism of testosterone 8. Is testis the only source of androgens? Why?

The testis is not the sole source of androgens: adrenal DHEA(S) is the main source in women, but biologically negligible in healthy mean

VII. Androgen production in the testes - Transport and metabolism of testosterone 9. What are Pleiotropic effects of testosterone?

Testosterone is responsible for - development of internal male genitalia (epididymis, vas deferens, seminal vesicle) - growth of penis - sperm production - imprinting of male pattern of gonadotropins - sexual drive + behavior and deepening of voice

VII. Androgen production in the testes - Transport and metabolism of testosterone 9. What is the role of Dihydrotestosterone?

Dihydrotestosterone is responsible for - development of external male genitalia (penis, scrotum, urethra, prostate) - beard growth - sebum formation + pubertal development => all together with testosterone

VII. Androgen production in the testes - Transport and metabolism of testosterone 10. Is testosterone important in both sexes? How?

VIII. Hypothalamic-pituitary-gonadal axis 1. Which hormone(s) that regulate testis?

The testis is regulated by LH and FSH

VIII. Hypothalamic-pituitary-gonadal axis 2. What are the features of regulation of testis?

VIII. Hypothalamic-pituitary-gonadal axis 3A. What is the general molecular mechanism of LH & FSH?

VIII. Hypothalamic-pituitary-gonadal axis 3B. What is the molecular mechanism of LH receptor?

Leydig cells express the LH receptor (Gs-coupled): - Increases the expression of enzymes and other proteins required for testosterone production (Sterol carrier protein and StAR)

VIII. Hypothalamic-pituitary-gonadal axis 3B. What is the molecular mechanism of FSH receptor?

Sertoli cells express the FSH receptor (Gs-coupled): - FSH binding increases the expression of ABP + aromatase (CYP19) and production of growth factors + inhibins

VIII. Hypothalamic-pituitary-gonadal axis 4. Make a schematic diagram for Hypothalamic-pituitary-gonadal axis

VIII. Hypothalamic-pituitary-gonadal axis 5. Why is it important to have high intratubular [testosterone]?

VIII. Hypothalamic-pituitary-gonadal axis 6A. What happen if there is Addition of external testosterone?

IX. Further parts of the male reproductive tract 1. What are the features of spermaturation

IX. Further parts of the male reproductive tract 2. What are the features of storage and emission?

IX. Further parts of the male reproductive tract - Formation of semen 4A. What are the 3 organs involved in the production of semen?

1) Seminal vesicles 2) Prostate (DHT dependent) 3) Bulbourethral glands (Cowper)

IX. Further parts of the male reproductive tract - Formation of semen 4B. How are seminal vesicles involved in the production of semen?

- 65-70% of semen volume - Fructose (energy source) - Fibrinogen + semenogelins (coagulation of sperm) - Prostaglandins (immunomodulatory in female)

IX. Further parts of the male reproductive tract - Formation of semen 4C. How is prostate involved in the production of semen?

Prostate (DHT dependent): - 25-30% of semen volume - Prostate specific antigen (PSA), fibrinolysin - Citrate, Zn2+, spermine and phosphatase

IX. Further parts of the male reproductive tract - Formation of semen 4D. How are Bulbourethral glands (Cowper) involved in the production of semen?

- 3-5% of semen volume - Produces mucus, pre-ejaculate => Complete activation of sperm cells in female genital tract only! Capacitation

IX. Further parts of the male reproductive tract - Formation of semen 5. What are important values in normal semen? (volume, pH,..)

- Volume = >1,5mL - pH=7,2–8,0 - 39 million spermatozoa/ejaculate (should not be any less than 15 million/μL) - More than 40% should show motilitly after 60 mins - More than 4% should show normal morphology

X. Erectile function 1. What are the 2 states of erectile function?

1. Flaccid state 2. Erect state

X. Erectile function 2. What happen in Flaccid state?

X. Erectile function 3. What happen in Erect state?

X. Erectile function 4A. What is the molecular mechanism of erection in Flaccid state?

X. Erectile function 4B. In flaccid state, what does sympathetic nerve endings do?

X. Erectile function 4C. In flaccid state, what is the role of Endothelial cell?

- Endothelial cell: will produce endothelins + prostaglandins, which act on G-protein (Gq) and will have the same effects as α1 receptors

X. Erectile function 5A. What is the molecular mechanism of erectile function in erect state?

X. Erectile function - Erect state 5B. What type of control is erect state under?

PARA control

X. Erectile function - Erect state 5C. In erect state, what is the role of PARA nerve endings?

X. Erectile function - Erect state 5D. What is PDE5?

PDE5 is an anti-erection agent that is inhibited by sildenafil (Viagra) - Viagra will inhibit PDE5 and thereby increase [cGMP] => dilation (erection)

X. Erectile function - Erect state 5E. What is the role of Non-adrenergic/noncholinergic neurons in erect state?

Non-adrenergic/noncholinergic neurons also release VIP (Gs) => ↑cAMP => ↓[Ca2+] => SMC relaxation

X. Erectile function - Erect state 5F. In erect state, What is the effect of ACh?

- The released ACh can pre-synaptically inhibit the SYM nerves - ACH can also act on endothelial cells, cholinergic receptor (Gq) -> PLC -> ↑[Ca2+]IC

X. Erectile function - Erect state 5G. In erect state, What is the role of Endothelial cells?

Endothelial cells express endothelial NO synthase (eNOS) – activated by Ca2+ => produce NO => SMC relaxation

XI. Reflex control 1. What are the steps of the male sex act?

The male sex act is divided into 3 steps: erection, emission, ejaculation

XI. Reflex control 2. What are the 2 types of reflexes in male sex act?

XI. Reflex control 3A. What are the 4 phases of erection?

1) Flaccidity 2) Full erection 3) Emission 4) Detumescence

XI. Reflex control - Phases of erection 3B. What happen in phase 1: Flaccidity?

XI. Reflex control - Phases of erection 3C. What happen in phase 2: Full erection?

XI. Reflex control - Phases of erection 3D. What happen in phase 3: Emission?

XI. Reflex control - Phases of erection 3E. What happen in phase 4: Detumescence?

7.7B. Male reproductive physiology Flashcards

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