week 10 - testicular function Flashcards
spermatozoa / sperm
- No transcription
- No endoplasmic reticulum
- No cytoplasm
- Relies on post-translational modifications.
o Glycosylation
o Phosphorylation
o Disulphide cross linking, ubiquitination, acetylation and methylation
after ejaculation
Sperm – egg interaction is fertilisation
what is spermatogensis
Biological process of producing mature sperm cells, and occurs in the male gonad
the male reproductive organs
- Scrotum provides cooler environment compared to body
o 35-36 degrees C
Spermatogenesis
what
- 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)
post pubertal testis
- 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
stertoli cells
Critical for all aspect of spermatogenesis (nurse cells)
stertoli cells
Tight junction with…
adjacent Sertoli cells
- Maintain the spermatogonial stem cell niche
stertoli cells
form blood testis barrier…
tight Junction with adjacent sterol cells
1. Separates developing germ cells from immune system
2. Controlled chemical microenvironment for spermatogenesis
stertoli cells
Form intimate…
associations with germ cells (50-50)
o Adheres junction
stertoli cells
Form a syncytium-like epithelial monolayer in which…
germ cell embedded – gap junctions
o Exchange molecules and communication
stertoli cells
final process
o Phagocytose cytoplasm of spermatozoa
SPERIMATION
stertoli cells
Secrete fluid into…
lumen of seminiferous tubules which flush spermatozoa into rete testis and epididymis
stertoli cells
Secrete Inhibin and Androgen Binding Proteins to…
regulate and maintain spermatogenesis
spermatogenesis
process
- 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
mitotic proliferation
- 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
meiotic divisions
Meiosis I:
- Primary spermatocytes divide to form secondary spermatocyte
Meiosis II:
- Secondary spermatocytes divide to form haploid spermatid
Giving rise to variation
SPERMATOGENESIS
how XX or XY
1 primary spermatocyte (diploid) produces
–> 4 round spermatids (haploid)
so when join female
XX or XY
SPERM DEVELOPMENT
Spermatogonia (base)
–> spermatocytes
–> spermatids
–> (spermiogenesis)
–> spermatozoa (released into the lumen)
Spermatocytes and spermatids move into adluminal compartment disrupting junctions between Sertoli cells
CELL DIFFERENTIATION
- SPERMIOGENESIS / CYTODIFFERENTIATION
- 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
CELL DIFFERENTIATION
ACROSOME
- 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
CELL DIFFERENTIATION
FLAGELLUM
- 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
CELL DIFFERENTIATION
MITOCHONDRIA
- Helically arranged around first part of flagellum (midpiece)
- Energy for motility
CELL DIFFERENTIATION
CYTOPLASM
- 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
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
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
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
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
spermatogenesis
process (simple)
Spermatogonia → Primary spermatocytes → Secondary spermatocytes → Spermatids → Sperms
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
ENDOCRINE CONTROL OF SPERMATOGENESIS
- extra testicular regulation (puberty)
HYPOTHALAMUS
- Pulsative release of GnRH (gonadotropin-releasing hormone) which act on the anterior pituitary
ENDOCRINE CONTROL OF SPERMATOGENESIS
- extra testicular regulation (puberty)
ANTERIOR PITUITARY GONADOTROPHINS
FSH - follicle stimulating hormone
LH - luteinizing hormone
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
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)
androgen
inhibin
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
TESTICULAR HORMONES
inhibin
(protein heterodimer hormone)
- Produced by Sertoli cells
- Acts on pituitary gland
- Inhibit FSH production
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
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
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
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
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
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
