week 10 - testicular function Flashcards

1
Q

spermatozoa / sperm

A
  • No transcription
  • No endoplasmic reticulum
  • No cytoplasm
  • Relies on post-translational modifications.
    o Glycosylation
    o Phosphorylation
    o Disulphide cross linking, ubiquitination, acetylation and methylation
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2
Q

after ejaculation

A

Sperm – egg interaction is fertilisation

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3
Q

what is spermatogensis

A

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

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4
Q

the male reproductive organs

A
  • Scrotum provides cooler environment compared to body
    o 35-36 degrees C
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5
Q

Spermatogenesis
what

A
  • Start at puberty, caused by the initiation of pulsatile release of gonadotropin releasing hormone (GnRH) from the hypothalamus
  • Takes 74 days
  • Humans produce 1000 spermatozoa/heartbeat = 100-200 million/day
  • Poor quality:
    o 95% abnormally formed
    o 68% immotile
    o 42% dead

(cells are linked – cytoplasm holds them together)

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6
Q

post pubertal testis

A
  • Two products
    o Spermatozoa and hormones
  • Two compartments
    within seminiferous tubules (90%)
  • Sertoli cells
    o Nurture germ cells in testis
  • Developing germ cells
    o Spermatogenesis (haploid)
    o Spermiogenesis (differentiation into sperm cell)
    Between tubules (interstitial cells 10%)
  • Leydig cells
    o Androgen (mainly testosterone) producing cell
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7
Q

stertoli cells

A

Critical for all aspect of spermatogenesis (nurse cells)

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8
Q

stertoli cells
Tight junction with…

A

adjacent Sertoli cells
- Maintain the spermatogonial stem cell niche

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9
Q

stertoli cells
form blood testis barrier…

A

tight Junction with adjacent sterol cells
1. Separates developing germ cells from immune system
2. Controlled chemical microenvironment for spermatogenesis

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10
Q

stertoli cells
Form intimate…

A

associations with germ cells (50-50)
o Adheres junction

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11
Q

stertoli cells
Form a syncytium-like epithelial monolayer in which…

A

germ cell embedded – gap junctions
o Exchange molecules and communication

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12
Q

stertoli cells
final process

A

o Phagocytose cytoplasm of spermatozoa
 SPERIMATION

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13
Q

stertoli cells
Secrete fluid into…

A

lumen of seminiferous tubules which flush spermatozoa into rete testis and epididymis

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14
Q

stertoli cells
Secrete Inhibin and Androgen Binding Proteins to…

A

regulate and maintain spermatogenesis

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15
Q

spermatogenesis
process

A
  • At puberty, prospermatogonia (gonocytes) are reactivated and undergo mitosis in basal compartment of seminiferous tubule
  • Spermatogonia are a 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” spermatogonia will for “type A” spermatogonia and start process of spermatogenesis
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16
Q

mitotic proliferation

A
  • Each “type A” spermatogonium undergoes mitosis to form type B spermatogonia which divide again to form primary spermatocytes which will undergo meiosis
  • All primary spermatocytes are 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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17
Q

meiotic divisions

A

Meiosis I:
- Primary spermatocytes divide to form secondary spermatocyte
Meiosis II:
- Secondary spermatocytes divide to form haploid spermatid
Giving rise to variation

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18
Q

SPERMATOGENESIS
how XX or XY

A

1 primary spermatocyte (diploid) produces
–> 4 round spermatids (haploid)

so when join female
XX or XY

19
Q

SPERM DEVELOPMENT

A

Spermatogonia (base)
–> spermatocytes
–> spermatids
–> (spermiogenesis)
–> spermatozoa (released into the lumen)

Spermatocytes and spermatids move into adluminal compartment disrupting junctions between Sertoli cells

20
Q

CELL DIFFERENTIATION
- SPERMIOGENESIS / CYTODIFFERENTIATION

A
  • Round spermatids elongate to form spermatozoa
  • Sperm are highly specialsed
    o Although very simplistic
  • Formation of specialised sperm structure
    o Acrosome, centriole, flagellum, mitochondria, nucleus
21
Q

CELL DIFFERENTIATION
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
    o Aid penetration
22
Q

CELL DIFFERENTIATION
FLAGELLUM

A
  • Centrioles migrate to opposite end of nucleus to acrosome and form axoneme
  • For sperm movement through the female tract and penetration of the egg vestments
  • Sperm centrioles also important for 1st division of the zygote
23
Q

CELL DIFFERENTIATION
MITOCHONDRIA

A
  • Helically arranged around first part of flagellum (midpiece)
  • Energy for motility
24
Q

CELL DIFFERENTIATION
CYTOPLASM

A
  • Superfluous cytoplasm forms residual body (cytoplasmic droplet) which is phagocytosed. By Sertoli cells, loss of organelles such as ER
    o All our mitochondria derived from mother
  • Sperm have very little cytoplasm
25
CELL DIFFERENTIATION NUCELUS
- Sex determination (X or Y) - Reshaping and elongation of nucleus - Sperm DNA becomes highly condensed o Histones replaced by protamines  Protect paternal genome during transport male and female reproductive tracts - Transcriptionally and translationally inactive o Because of protamines During nuclear chromatin re-organisation in spermiogenesis: - Somatic histones are firstly replaced by testis-sepcific histone variants - Transition proteins are incorporation in the nuclei of spermatids - Protamine’s then replace transition proteins in the late spermatids to pack genome into the highly condensed sperm nucleus o So no transcritption factors can reach DNA
26
DEVELOPING SPERM CELLS FORM A SYNCYTIUM
- Share cytoplasm - During meiosis and mitosis cytokinesis is incomplete o Intercellular bridges - Syncytia persist until final stages of spermatogenesis
27
DEVELOPING SPERM CELLS FORM A SYNCYTIUM - FUNCTION
- Allows sharing of cytoplasmic components o 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
28
SPERMATOGENESIS - SPERMIATION
- Last step of spermatogenesis - Facilitated by Sertoli cell cytoskeleton - Cytoplasmic bridges rupture (syncytium) - Loss of spermatids cytoplasm o Absorbed by the Sertoli cell (phagocytosis) - Sperm are released into lumen of seminiferous tubule in testis
29
spermatogenesis process (simple)
Spermatogonia → Primary spermatocytes → Secondary spermatocytes → Spermatids → Sperms
30
ENDOCRINE CONTROL OF SPERMATOGENESIS Hypothalamus-Pituitary-Gonadal Axis
- Controlled by products released by testis somatic cells: o Within tubules  Sertoli cells o Between tubules  Leydig cells
31
ENDOCRINE CONTROL OF SPERMATOGENESIS - extra testicular regulation (puberty) HYPOTHALAMUS
- Pulsative release of GnRH (gonadotropin-releasing hormone) which act on the anterior pituitary
32
ENDOCRINE CONTROL OF SPERMATOGENESIS - extra testicular regulation (puberty) ANTERIOR PITUITARY GONADOTROPHINS
FSH - follicle stimulating hormone LH - luteinizing hormone
33
ENDOCRINE CONTROL OF SPERMATOGENESIS - extra testicular regulation (puberty) ANTERIOR PITUITARY GONADOTROPHINS FSH
o Acts on testis (Sertoli cells) to maintain spermatogenesis o Binds to FSH receptor on Sertoli cells o Induce expression of androgen receptors on Sertoli cells, increasing their responsiveness to androgens o Stimulates production od ABP (androgen binding protein) by Sertoli cells o Stimulates production of inhibin by Sertoli cells
34
ENDOCRINE CONTROL OF SPERMATOGENESIS - extra testicular regulation (puberty) ANTERIOR PITUITARY GONADOTROPHINS LH
o Binds to LH receptors mainly on Leydig cells (but also on Sertoli cells) o Induce Leydig cells to produce androgen (testosterone)
35
TESTICULAR HORMONES -
androgen inhibin
36
TESTICULAR HORMONES androgen
(testosterone – steroid hormone) - Development of testis (embryo) - Sexual function and characteristic (puberty) - Reproductive function (adult) - Produced by Leydig cells (between tubules) - Mainly testosterone: o Carried by ABP (androgen binding protein) in testicular fluid o Converted to dihydrotestosterone (by 5alpha-reductase in Sertoli cells) o Binds and affects Sertoli cells’ function - Negative feedback on hypothalamus and anterior pituitary by repressing LH and FSH production
37
TESTICULAR HORMONES inhibin
(protein heterodimer hormone) - Produced by Sertoli cells - Acts on pituitary gland - Inhibit FSH production
38
ROLE OF TESTICULAR PRODUCT
Androgen Binding protein (ABP) - Product of Sertoli cells under testosterone stimulation - Binds and carries testosterone in testicular fluid of seminiferous tubules - Maintain high levels of testosterone 100x more concentrated than blood o Testosterone lipid soluble and diffuse across plasma membrane o Binding to ABP prevents diffusion and increase concentration
39
MOVEMENT OF SPERM IN SEMINIFEROUS TUBULES AND RETE TESTIS
- Spermatozoa released from testis are immotile until they traverse epididymis o Acquired caput - No cilia o 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 o Peristalsis
40
SPERM MATURATION AND TRANSPORT
- Human sperm are 10-15um in length o Have to transverse 30-40cm of male and female reproductive tract to reach the oocyte - ~1 in a million complete the journey - Post testis: o Sperm need to undergo sperm maturation in the male tract (epididymis) and capacitation (further changes) in the female tract o Important for the acquisition of motility and fertility potential
41
EPIDIDYMAL MATURATION (sperm maturation)
- Highly segmented organ that is divided in 3 main anatomic regions CAPUT - close testis (motility) CORPUS - fertilising ability CAUDA/ VAS DEFERENS - storage VAS DEFERENS Each segment: - Displays different expression of genes - Maintains luminal ions concentrations - Essential to regulate steps of sperm maturation
42
EPIDIDYMAL MATURATION (sperm maturation)
Sperm changes during epididymal transit - Sperm interact with epididymal epithetical cells (removal of cytoplasmic droplet) o Retention of cytoplasmic droplet is associated with reduced fertility - Change sperm proteome – protein, lipid and sugar content o Incorporated into the sperm cells - Change in sperm surface o Removal and/or modification of external proteins, sugars and lipid sperm membrane - Intracellular signalling pathways activation during transit o Addition or removal of protein phosphate groups (phosphorylation
43
EJACULATION
- Sperm (2-5%) + seminal plasma = semen - Approx. 3ml in human (~100 million sperm) - Seminal plasma is secreted by the accessory sex glands o seminal vesicles, prostate, Bulbourethral gland - transport, nutrition, buffering, antioxidants
44