ERS28 Spermatogenesis Flashcards

1
Q

Spermatogenesis

A
  • within Seminiferous tubules
  • 60-70 days (imply treatment inducing spermatogenesis takes 60-70 days)
  • 1 spermatogonium —(4 mitosis + 1 meiosis)—> 64 spermatozoa
    (NO unequal cell division)
Direction:
Seminiferous tubules
—> Rete testis
—> Efferent tubules (Vasa efferentia)
—> Epididymis (***Caput + ***Corpus + ***Cauda) (coiled tube)
—> Vas deferens

Epididymis epithelium: Pseudostratified columnar epithelium with Stereocilia

Cilia越黎越短, Lumen越黎越大

Caput Epididymis:

  • ciliated epithelium
  • small lumen
  • absorption of testicular fluid to concentrate sperm

Corpus Epididymis:

  • shorter cilia
  • wider lumen
  • absorption of testicular fluid to concentrate sperm

Cauda Epididymis:

  • cuboidal, poorly ciliated epithelium
  • wide lumen
  • small muscle cells
  • ***store sperm at high density

Time required for sperm to travel through Epididymis —> 2-6 days
- not related to length

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2
Q

Testis

A
  1. Reproductive organ (Seminiferous tubule) —> Spermatogenesis
  2. Endocrine organ (Leydig cells) —> Male sex hormone (Testosterone)
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3
Q

Germ cells in mature testes

A

Puberty
—> **Spermatogonia (2N, 2C) (periphery of Seminiferous tubules) (Undergo mitosis / **Self-renewal / Proliferating phase)
—> DNA replication
—> **Primary Spermatocyte (2N, 4C)
—> Meiosis 1
—> **
Secondary Spermatocyte (1N, 2C)
—> Meiosis 2
—> Spermatids (1N, 1C) (non-motile, without tail) (closer to lumen of Seminiferous tubules)
—> Morphological changes (
Spermiogenesis)
—> ***Spermatozoa (1N, 1C)

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4
Q

***Difference between Spermatogenesis and Oogenesis.

A
  1. NOT all spermatogonia will undergo meiotic division
    —> some will go back to stem cell pool
    —> **self-renewal to produce more spermatogonia
    —> **
    “unlimited” number of spermatocytes
  2. Presence of additional step after formation of spermatids: ***Spermiogenesis
    —> transformation of spermatids into sperm
    —> change in morphology
  3. Meiosis start **before birth in Oogenesis
    —> ALL oogonia undergo meiosis
    —> Primary oocyte
    —> set ceiling of finite number of oocytes in a female
    VS
    Spermatogonia remain dormant until after puberty, Meiosis start **
    at puberty
  4. **Prolonged cell division in Oogenesis (from fetal period to after fertilisation)
    - enable external factor to affect division process
    —> female Oogenesis **
    higher aneuploidy rate with age
    VS
    Spermatogenesis start after puberty, ***once started go to completion (uninterrupted)
  5. Equal cell division in Spermatogenesis
    VS
    Unequal cell division in Oogenesis
  6. 4 functional spermatozoa in Spermatogenesis (vs 1 functional oocyte each meiosis)
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5
Q

Seminiferous tubule structure

A
  1. Myoid cells
    - smooth muscles cells
    - contraction of tubule, propel content towards Rete testis
  2. Leydig cells
    - Testosterone production
  3. Sertoli cells
    - Blood-testes barrier
    —> separate Seminiferous tubules into Adluminal + Basal compartment
    —> Tight junction: important in controlling material going into Seminiferous tubules
    - **Spermatogonia outside of tight junction (i.e. in Basal compartment)
    —> **
    Primary spermatocytes move across Blood-testes barrier
    —> into Adluminal compartment
  4. Spermatogonia —> Spermatozoa
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6
Q

Basal vs Adluminal compartment

A

Basal compartment:
—> **Proliferating phase, **Self-renewal
- Spermatogonia

Adluminal compartment:
—> **Meiosis
—> **
Spermiogenesis (differentiation into spermatozoa)
- Primary / Secondary Spermatocytes, Spermatids, Spermatozoa

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7
Q

Tight junctions

A

Dynamic structure
- always assemble / disassemble —> allow germ cells to move across barrier
- form behind moving Preleptotene / Leptotene spermatocytes
—> disassembly of tight junction in front of cells

**Preleptotene (DNA synthesis) / **Leptotene spermatocytes move inwards towards lumen

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8
Q

Spermiogenesis

A
  1. Formation of ***Acrosome granule (small vesicle covering one side of spermatid nucleus)
    —> contain Enzymes (Acrosin)
    —> grow in size
    —> cover anterior 1/3 of sperm nucleus
  2. Formation of **Sperm tail
    —> Opposite side to Acrosome granule
    —> **
    Mitochondria of spermatid move from periphery of spermatid towards sperm tail
    —> within ***Midpiece
  3. Condensation of nucleus of spermatid
    —> replacement of Histone protein by ***Protamine
  4. Shrinkage of cytoplasm
    —> sperm contains mainly **DNA + **Mitochondria
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9
Q

Structure of mature sperm

A
  1. Head
    - Nucleus (condensed) covered on one side by Acrosome
    - Acrosome
    —> covered outside by plasma membrane
    —> outer + inner membrane
    —> enzyme to help penetrate **Zona pellucida + Cumulus mass (i.e. **Corona radiata)
  2. Midpiece
    - Mitochondria
    —> **produce energy for sperm movement
    —> **
    Ca storage
  3. Tail
    - Active propulsion of sperm
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10
Q

Low temperature is important for spermatogenesis

A
  1. Testicular temperature in Scrotum: ***2oC lower than Body temp
  2. Descent of testis at birth important
  3. Temperature regulation
    - ***Musculature of scrotum (Dartos muscle)
    —> contraction in cold temperature to press testes towards body core
    —> relax in hot temperature to allow testes to descend
  • ***Counter current heat exchange
    —> testicular arteries in parallel with veins
    —> when hot arterial blood enter testes —> embedded in network of veins (lower temp)
    —> cooled down by cold blood in testicular veins
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11
Q

Lifestyle affects sperm quality

A

Regular hot bath
—> ↓ sperm count
—> ↓ motility
—> poor morphology

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12
Q

Spermiation

A

Process in which Spermatozoa extruded into lumen of Seminiferous tubule (~ ovulation)

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13
Q

Sperm maturation in Epididymis

A

Transportation of sperm to Epididymis

  • Tubular fluid current created by contraction of peritubular ***Myoid cells (move from Seminiferous tubules towards Rete testis)
  • Contraction of ***testicular capsule (Tunica albuginea)

Changes during maturation:

  1. Marked changes in osmolality
    - ***Concentration of osmolytes, molecules in Epididymis
  2. ***Gain motility
  3. ***Lose cytoplasm
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14
Q

Capacitation

A
  • ***Sperms acquire ability to fertilise ovum
  • Occur in female reproductive tract
  • Ill-defined process

End point:

  1. Hyperactivation
    - special motility pattern after capacitation —> ↑ amplitude, not necessarily forward (活躍地亂咁走) (Non-hyperactivated: slow, progressive linear forward)
  2. Acrosome reaction
    - fusion of Acrosomal + Outer sperm membrane
    —> pores on sperm head
    —> release of **hydrolytic + **proteolytic enzymes
    —> penetration through **Zona pellucida, **Cumulus mass
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15
Q

***Sertoli cells

A
  1. Regulate nutrients + environment for Spermatogenesis
    - Tight junctions / Blood testes barrier
    —> separating pre (Spermatogonia) / post meiotic germ cells (Primary spermatocytes)
  2. Endocrine / Paracrine function
    - ***Anti-Mullerian hormone (AMH) —> regression of Müllerian ducts before puberty
  • **Androgen binding protein (ABP) —> T becomes less lipophilic —> **concentrate in luminal fluid —> high Testosterone —> enable spermatogenesis + maturation
  • ***Plasminogen activator —> Spermiation
  • ***Inhibin / Activin —> regulate Testosterone
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16
Q

Inhibin and Activin

A

Inhibin:

  • ↓ FSH production (Testosterone -ve feedback to FSH)
  • ***↑ Testosterone production from Leydig cells

Activin:

  • ***↑ FSH production
  • ↓ Testosterone production from Leydig cells
17
Q

Peritubular Myoid cells

A
  1. Move spermatozoa to Rete testis by contraction

2. Modulate function of other testicular cells e.g. Sertoli cells, Leydig cells

18
Q

Leydig cells

A

Testosterone production

Under pituitary LH control

Testosterone
- circulating
- prohormone of DHT (Dihydrotestosterone)
—> T converted to DHT in tissue

19
Q

Testosterone in male

A

Ability to produce Testosterone acquired before birth at fetal stage

  • **3 peaks:
    1. After fertilisation
    2. Immediately after birth
    3. After puberty

Function:
Note: Precursor in some tissues (need to convert to DHT: more active / E2)
1. Intrauterine development of male reproductive tract
2. Puberty development
3. Spermatogenesis
4. Sex drive
5. Muscle, Skeleton, Body fat

20
Q

Conversion of Testosterone to Estrogen

A

Which steroid to produce depends on

  1. Availability of enzymes
  2. Activity of enzymes

E.g. High Aromatase activity —> Androgen rapidly converted into Estrogen

Cholesterol
—> Progesterone
—> Corticosteroid (Cortisol, Aldosterone) / Androgen (T, Androstenedione) —> Estrogen (Estradiol, Estrone, Estriol)

21
Q

***Interaction among Testicular cells (Leydig, Sertoli, Myoid, Germ cells)

A

Interactions are localised: different position of seminiferous tubule —> different interaction (stimulatory / inhibitory)

LH —(+ve)—> Leydig (~ Theca) —> Testosterone —(+ve)—> Myoid + Sertoli

FSH —(+ve)—> Sertoli (~ Granulosa)

Myoid —(+ve, Proteins)—> Sertoli

  • **Sertoli
    1. ABP —> ↑ Testosterone
    2. Nutrients, Growth factors, ABP —(+ve)—> Germ cell
  • **3. Activin, Estradiol —(-ve)—> Leydig —> ↓ Testosterone
  • **4. Inhibin —(+ve)—> Leydig —> ↑ Testosterone

Germ cell
Growth factors —(+ve)—>
1. Leydig
2. Sertoli

22
Q

***Gonadotropin and Spermatogenesis

A

Testosterone: Absolute requirement for spermatogenesis (without T, stop at Preleptotene stage (DNA synthesis))
—> -ve feedback to Gonadotropin

Initially:
- Normal FSH, LH, Testosterone —> High Sperm density

High Testosterone
—> inhibit FSH + LH
—> Sperm density ↓ greatly (太高Testosterone反而令Sperm density ↓ ∵ ↓ FSH, LH)
—> Give FSH, LH
—> Sperm density ↑ slightly but not reach level before

Conclusion:
**Both FSH, LH are also required for **quantitative spermatogenesis

23
Q

Regulation of spermtogenesis by LH + FSH

A
  1. LH
    —> Leydig
    —> ***Testosterone (absolute requirement for initiation + maintenance of spermatogenesis)
    —> Sertoli + Myoid (Androgen receptors)
  2. FSH
    - **proliferation of Sertoli in mature testes —> Testicular development
    - act on Sertoli cells —> indirectly regulate **
    Mitosis of Spermatogonia + prevent degeneration
24
Q

Regulation of spermatogenesis on Hypothalamic-pituitary-gonad axis

A

LH —> Leydig —> **Testosterone —> -ve feedback on **Gonadotropin + GnRH

FSH —> Sertoli —> **Inhibin —> -ve feedback on **FSH only but +ve to Leydig

25
Q

Testosterone and Sexual behaviour

A

T implant into Preoptic areas, Anterior hypothalamus
—> produce similar response to systemic injection of T

Conclusion:
Testosterone act on **Preoptic areas, **Anterior hypothalamus to enhance sexual behaviour

26
Q

Male sex act

A

3 stages
1. Erection of penis
- activation of **PNS —> **Vasodilation —> Filling of vascular structure within penis
—> Corpus cavernosum + Corpus spongiosum
—> veins in penis compressed when erectile tissues filled with blood
—> ↓ blood outflow from penis

  • Ischiocavernosus muscle + Bulbospongiosus muscle
    —> assists in Micturition + Erection
    —> compress Bulb of penis
    —> pull Root of penis (Crus + Bulb) —> erection
  1. Emission
    - activation of **SNS
    —> Contraction of **
    Vas deferens + **Male sex accessory glands
    —> Semen formation in **
    prostatic urethra
  2. Ejaculation
    - filling of prostatic urethra
    —> Rhythmical contraction of genital duct + Contraction of Ischiocavernosus muscle / Bulbospongiosus muscle
    —> ejaculation
    - 40-80 million sperms in 2-4 mL
    - Emission + Ejaculation occur during Orgasm
27
Q

WHO reference ranges for normal Semen

A
  1. Volume >= 1.5 mL
  2. pH >= 7.2 (Alkaline)
  3. Concentration
  4. Count
  5. Motility (<1 hour)
  6. Morphology
28
Q

Sperm morphology abnormalities

A
  1. Head defects
  2. Neck and Midpiece defects
  3. Tail defects
  4. Cytoplasmic defects
29
Q

Semen

A

Seminal plasma + Spermatozoa

Seminal plasma:

  • Sex accessory glands
  • Alkaline —> neutralise acidity of female tract
  • Most spermatozoa expelled with prostatic secretion in first 1/3 of ejaculate —> need to collect whole semen sample (later part of Ejaculate contain less sperm —> not accurate)
30
Q

Bulbourethral gland (Cowper’s gland)

A
  • 5% ejaculate volume
  • clear, **alkaline, mucoid fluid produced on sexual stimulation (pre-ejaculate) into urethra
    —> **
    lubricant for semen
    —> lubricant for Glans penis during intercourse
    —> ***neutralise acidity of urine residue in urethra + acidity of vagina
31
Q

Seminal vesicles

A
  • 50-80% of ejaculate volume
  • last fraction of ejaculate
  • rich in
    1. Fructose (energy)
    2. Ascorbic acid (antioxidant)
    3. **Stimulators of sperm motility: K, HCO3, Mg, Prostaglandin
    4. **
    Semenogelin (protein) —> Coagulum formation, ***inhibit sperm capacitation before passing through cervical canal
    —> capacitated sperm have limited lifespan
    —> early capacitation not allow enough time for sperm to swim to Fallopian tube
32
Q

Prostate gland

A
  • 15-30% ejaculate volume
  • main source of
    1. Citric acid —> antioxidant
    2. **Zinc —> antioxidant + **sperm chromatin stabilisation
    3. **Prostatic acid phosphatase, **Prostate-specific antigen (PSA)
    —> **Semenogelins cleavage
    —> allow sperm to **
    swim and capacitation