LECTURE 27 - testicular function Flashcards
What does the presence of the Y chromosome lead to?
- 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
What is puberty?
- 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
What is the structure of the male reproductive organs?
- 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
What are the 2 products of post-pubertal testis?
- spermatozoa
2. hormones
What are the 2 compartments of the post-pubertal testis?
- 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) - Between seminiferous tubules (10%)
- Leydog cells: androgen (mainly testosterone) producing cell
What are Sertoli cells?
- 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
What is the blood-testis barrier?
- 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
What are the functions of the blood-testis barrier?
- Separates developing germ cells from immune system preventing immune response (anti-sperm antibodies and autoimmune orchitis - sub fertility)
- Controlled chemical microenvironment for spermatogenesis (selective transport of ions and small molecules)
What is spermatogenesis?
- in humans starts at puberty, takes 74 days, produce 1000 spermatozoa/ heartbeat
- 1 primary spermatocyte (diploid) –> 4 round spermatids (haploid)
What are the 3 phases of spermatogenesis?
- Proliferation (mitosis)
- expand in cell number (diploid cells) - Division (meiosis)
- spermatogonia become spermatocytes to produce haploid spermatid - Differentiation
- spermiogenesis
What are prospermatogonia and what happens to them at puberty?
- 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
Describe the mitotic proliferation of spermatogonium
- 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
Describe briefly sperm development
PGC –> prospermatogonia –> AS spermatogonia –> A spermatogonia –> B spermatogonia –> primary spermatocyte –> meiosis to form spermatids –> spermiogenesis to form spermatozoa in lumen
What happens in the meiotic divisions?
Meiosis I: primary spermatocytes divide to form secondary spermatocyte
Meiosis II: secondary spermatocytes divide to form haploid spermatid (round)
–> spermiogenesis forms actual sperm (spermatozoa)
What is spermiogeneis/ cytodifferentiation?
- round spermatids elongate to form elongated spermatozoa
- sperm are highly specialised although very simplistic
- sperm made up of:
acrosome, centriole, flagellum, mitochondria, nucleus
What is the 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 and aid in penetration
- has two membranes that fuse when egg plasma membrane is met to allow contents to be released
What is the flagellum?
- 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
What are mitochondria?
- helically arranged around first part of flagellum (midpiece)
- energy for motility
What is the nucleus?
- sex-determination (X or Y)
- reshaping and elongation of nucleus
- sperm DNA becomes highly condensed - histones replaced by protamines
- transcriptionally and translationally inactive
What is the cytoplasm?
- 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
What is a syncytium and what is its function?
- 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)
What is spermiation?
- 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
How do sperm move into seminiferous tubules and rete testis?
- 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
Describe the endocrine control of testicular function
- 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
How does FSH act on Sertoli cells?
- 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
How does LH act?
- binds to LH receptors mainly on Leydig cells but also sertoli cells
- induce Leydig cells to produce androgen (testosterone)
What does testosterone do?
- 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
What does inhibin do?
- produced by sperm cells
- acts on pit. gland
- inhibits FSH production
What does the androgen binding protein (ABP) do?
- 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
What can a high/low FSH/LH levels show?
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
What can high/low testosterone levels indicate?
Shown in blood test
Testosterone measured with LH/FSH test
Low
- hypothalamic and pit. disease
- damage to testis
High
- testicular tumour
How do mature sperm reach the oocyte?
- 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
What is the epididymus?
- 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
What is epididymal maturation (sperm maturation)?
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)
What is ejaculation?
- 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
