LECTURE 27 - testicular function Flashcards

1
Q

What does the presence of the Y chromosome lead to?

A
  • leads to testis formation under hormonal regulation (androgen) in embryo
  • has a controller gene
    > sex-determingin region of Y gene (SRY)
    > produced testis determine factor from week 6-7
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2
Q

What is puberty?

A
  • dependent on attainment of critical body weight/fat
  • complex process involving secondary sexual characteristic development and accelerated growth
  • initiation of gametogenesis (spermatogenesis - haploid sperm)
  • caused by initiation of pulsatile release of GnRH from hypothalamus
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3
Q

What is the structure of the male reproductive organs?

A
  • within testis there are seminiferous tubules, within lumens spermatogenesis will occur)
  • sperm released in lumen will join in epididymis
  • small proportion of sperm travels along vas deferens gets mixed with secretion from seminal vesicles and prostate and come out of urethra
  • scrotum provides cooler environment compared to body
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4
Q

What are the 2 products of post-pubertal testis?

A
  1. spermatozoa

2. hormones

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5
Q

What are the 2 compartments of the post-pubertal testis?

A
  1. Within seminiferous tubules (90%)
    - Sertoli cells: nurture germ cells in testis
    - developing germ cells
    > spermatogenesis (formation of mature spermatozoa)
    > spermiogenesis (differentiation from round to elongated cell)
  2. Between seminiferous tubules (10%)
    - Leydog cells: androgen (mainly testosterone) producing cell
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6
Q

What are Sertoli cells?

A
  • critical for all aspects of spermatogenesis - nurse cells
  • secrete inhibit and androgen binding proteins to regulate and maintain spermatogenesis
  • maintenance of spermatogonial stem cell niche
  • form intimate associations with germ cells - tight junctions
  • form a syncytium-like epithelial monolayer in which germ cell embedded - gap junctions (exchange molecules and communication)
  • form blood testis barrier - tight junction with adjacent Sertoli cells
  • final process, phagocytosis - spermination
  • secrete fluid into the lumen of seminiferous tubules which flush spermatozoa into rete testis and epididymis
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7
Q

What is the blood-testis barrier?

A
  • between basal and apical compartments of tubule
  • gap and tight junctions link each sertoli cell to its neighbour
  • develops during puberty prior to onset of spermatogenesis
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8
Q

What are the functions of the blood-testis barrier?

A
  1. Separates developing germ cells from immune system preventing immune response (anti-sperm antibodies and autoimmune orchitis - sub fertility)
  2. Controlled chemical microenvironment for spermatogenesis (selective transport of ions and small molecules)
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9
Q

What is spermatogenesis?

A
  • in humans starts at puberty, takes 74 days, produce 1000 spermatozoa/ heartbeat
  • 1 primary spermatocyte (diploid) –> 4 round spermatids (haploid)
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10
Q

What are the 3 phases of spermatogenesis?

A
  1. Proliferation (mitosis)
    - expand in cell number (diploid cells)
  2. Division (meiosis)
    - spermatogonia become spermatocytes to produce haploid spermatid
  3. Differentiation
    - spermiogenesis
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11
Q

What are prospermatogonia and what happens to them at puberty?

A
  • neonatal male germ cells
  • at puberty, prospermatogonia reactivated and undergo mitosis in basal compartment of seminiferous tubule
  • AS spermatogonia are reservoir of self renewal stem cells (maintain germ cell line) and remain in outer edge of tubule as undifferentiated spermatogonia
  • some AS spermatogonia will form type A spermatogonia and start process of spermatogenesis
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12
Q

Describe the mitotic proliferation of spermatogonium

A
  • each A spermatogonium undergoes mitosis to form type B spermatogonia which divide again to form primary spermatocytes which will undergo meiosis
  • all primary spermatocytes are genetically identical to spermatogonia
  • primary spermatocytes move towards lumen and through blood testis barrier
  • primary spermatocytes enter a resting phase where chromosomes duplicate ready for first meiotic division
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13
Q

Describe briefly sperm development

A

PGC –> prospermatogonia –> AS spermatogonia –> A spermatogonia –> B spermatogonia –> primary spermatocyte –> meiosis to form spermatids –> spermiogenesis to form spermatozoa in lumen

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14
Q

What happens in the meiotic divisions?

A

Meiosis I: primary spermatocytes divide to form secondary spermatocyte

Meiosis II: secondary spermatocytes divide to form haploid spermatid (round)

–> spermiogenesis forms actual sperm (spermatozoa)

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15
Q

What is spermiogeneis/ cytodifferentiation?

A
  • round spermatids elongate to form elongated spermatozoa
  • sperm are highly specialised although very simplistic
  • sperm made up of:
    acrosome, centriole, flagellum, mitochondria, nucleus
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16
Q

What is the acrosome?

A
  • formed from Golgi apparatus which migrates to one end of nucleus
  • contains hydrolytic enzymes which are released upon binding to the zona pellucida of the egg and aid in penetration
  • has two membranes that fuse when egg plasma membrane is met to allow contents to be released
17
Q

What is the flagellum?

A
  • centrioles migrate to opposite end of nucleus to acrosome and form axoneme
  • form sperm movement through the female tract and penetration of the egg vestments
  • sperm centrioles also important for 1st division of the zygote
18
Q

What are mitochondria?

A
  • helically arranged around first part of flagellum (midpiece)
  • energy for motility
19
Q

What is the nucleus?

A
  • sex-determination (X or Y)
  • reshaping and elongation of nucleus
  • sperm DNA becomes highly condensed - histones replaced by protamines
  • transcriptionally and translationally inactive
20
Q

What is the cytoplasm?

A
  • superfluous cytoplasm forms residual body (cytoplasmic droplet) which is phagocytosis by Sertoli cells, loss of organelles such as ER (cannot translate any proteins)
  • sperm have very little cytoplasm
21
Q

What is a syncytium and what is its function?

A
  • during mitosis and meiosis cytokinesis is incomplete - forms intercellular bridges
  • syncytia persist until final stages of spermatogenesis

Function:
- allows sharing of cytoplasm components e.g. developing sperm that carry a Y chromosome, can be supplied with essential proteins encoded by genes on the X chromosome (axoneme and acrosome)

22
Q

What is spermiation?

A
  • last step of spermatogenesis
  • facilitated by Sertoli cell cytoskeleton
  • cytoplasmic bridges rupture (syncytium)
  • loss of spermatid cytoplasm - anchor with the Sertoli cell
  • sperm are released into lumen of seminiferous tubule in testis
23
Q

How do sperm move into seminiferous tubules and rete testis?

A
  • spermatozoa released form testis are immotile until transverse epididymis (acquired caput)
  • no cilia but fluid secretions from Sertoli cells and smooth muscle-like cells in testicular tunic and lamina propria (collagen and elastin) of seminiferous tubules
  • periodic powerful contraction - peristalsis
24
Q

Describe the endocrine control of testicular function

A
  • at puberty hypothalamus releases GnRH, levels only controlled if testis is working (controlling via hormones)
  • LH and FSH released by ant. pit.
    FHS acts on Sertoli cells to maintain spermatogenesis
  • LH acts on leydig cells
25
Q

How does FSH act on Sertoli cells?

A
  • binds to FSH receptor on sertoli cells
  • induces expression of androgen receptors increasing responsiveness to androgens
  • stimulates production of ABP (androgen binding protein) by serotli cells
  • stimulates production of inhibit by Sertoli cells
26
Q

How does LH act?

A
  • binds to LH receptors mainly on Leydig cells but also sertoli cells
  • induce Leydig cells to produce androgen (testosterone)
27
Q

What does testosterone do?

A
  • development of testis (embryo)
  • sexual function and characteristics (puberty)
  • reproductive function (adult)
  • produced by Leydig cells (between tubules)
  • carried by ABP in testicular fluid
  • converted to dihydrotestosterone (by 5a-reductase)
  • bind and effect Sertoli cells function
  • -ve feedback on hypothalamus and ant. pit. by repressing LH and FHS production
28
Q

What does inhibin do?

A
  • produced by sperm cells
  • acts on pit. gland
  • inhibits FSH production
29
Q

What does the androgen binding protein (ABP) do?

A
  • produced by Sertoli cells under testosterone stimulation
  • binds and carries testosterone in testicular fluid of seminiferous tubules
  • maintains high levels of testosterone (100x more concentrated than blood)
    • testosterone is lipid soluble and diffuses across plasma membrane
    • binding to ABP prevents diffusion and increases concentration
30
Q

What can a high/low FSH/LH levels show?

A

Found in blood test
FSH affects sperm production
LH stimulates testes to secrete testosterone

High FSH and LH

  • indicates failure of testicular function
  • acquired testicular damage

Low FSH and LH

  • indicate that testes not receiving adequate stimulatory message from hypothalamus and pit. (dysfunction)
  • congenital hypogonadism
31
Q

What can high/low testosterone levels indicate?

A

Shown in blood test
Testosterone measured with LH/FSH test

Low

  • hypothalamic and pit. disease
  • damage to testis

High
- testicular tumour

32
Q

How do mature sperm reach the oocyte?

A
  • human sperm are 10-15μm - have to traverse 30-40cm of male and female reproductive tract to reach oocyte
  • ~1 million complete the journey

Post testis: sperm need to undergo sperm maturation in the male tract (epididymis) and capacitation in the female tract
- important for the acquisition of motility and fertility potential

33
Q

What is the epididymus?

A
  • highly segmented organ that is divided into 3 main anatomic segments
    1. Caput - close testis (motility)
    2. Corpus (fertilising ability)
    3. Cauda/ vas deferens (storage)

Each segment

  • displays differential expression of genes
  • maintains luminal ions concentrations
  • -> essential to regulate steps of sperm maturation
34
Q

What is epididymal maturation (sperm maturation)?

A

Sperm changes during epididymal transit
Sperm interact with epididymal epithelial cells
- movement of cytoplasmic droplet
- retention of cytoplasmic droplet associated with reduced fertility

Change sperm proteome - protein, lipid and sugar content (incorporated into sperm cells)

Change in sperm surface
- removal and/or modification of external proteins, sugars and lipid sperm membrane

Intracellular signalling pathways activation during transit
- addition or removal of protein phosphate group (phosphorylation)

35
Q

What is ejaculation?

A
  • sperm (2-5%) + seminal plasma = semen
  • approx. 3ml in human ~100 million sperm
  • seminal plasma is secreted by the accessory sex glands (seminal vesicles, prostate, Bulbourethral gland)
  • transport, nutrition, buffering, antioxidants