At which point in development is the male reproductive system distinguishable from the female reproductive system?
Week 7
Which cells are the precursors to the reproductive systems?
What ploidy are these cells?
- Primordial germ cells
- Diploid cells
What is the role of the Y chromosome in the determination of male sex?
- The Y chromosome has the sex-determining region Y (SRY) gene (testis determining factor) that codes for an architectural transcription factor that binds DNA and allows other TFs to upregulate other male determining genes
- SRY doesn’t contain the genes for testis, but switches on other genes essential for their development
What is the cause of females with XY chromosomes and males with XX chromosomes?
- SRY gene mutation/deletion ➡ XY ‘females’
- SRY gene translocation onto the X or a somatic chromosome ➡ XX ‘males’
What processes occur from week 7 in male reproductive development?
1 - Columns of cells from the coelomic epithelium proliferate and penetrate deep into medullary mesenchyme
2 - These are the cells that express SRY and they form the primitive sex cords
3 - Primordial germ cells (PGCs) become surrounded by these sex cord cells
4 - This forms the seminiferous tubules
From which cells are Sertoli cells derived?
Mesodermal sex cord cells
From which cells are prospermatogonoia derived?
Primordial germ cells (PGCs)
What is the fate of migratory cells from the mesonephric primordia?
They form the vasculature, Leydig cells and myoid cells
What cellular event is inhibited within seminiferous tubules?
Meiosis is inhibited and cells become dormant
When does SRY stop being expressed?
What directs further development of the male reproductive system?
- Once seminiferous tubules have formed
- The testes direct further development via androgens from Leydig cells and anti-Mullerian hormone (AMH) from Sertoli cells
List the two compartments of post-pubertal testis.
Which cells are present in these compartments?
- Within the seminiferous tubules – sperm develop, under the influence of Sertoli cells
- Between the seminiferous tubules – Leydig cells
What is the function of the Sertoli cells in the seminiferous tubules of the post-pubertal testis?
To produce sperm
What is the function of the Leydig cells in the seminiferous tubules of the post-pubertal testis?
To produce androgens
Where is the blood-testis barrier?
Between the adluminal and basal compartments of the seminiferous tubules
List the junctions that form the blood-testis barrier.
Which cells are being linked together by these junctions?
1 - Adherens junctions
2 - Gap junctions
3 - Tight junctions
- These junctions are linking adjacent Sertoli cells
When does the blood-testis barrier develop?
During puberty prior to the onset of spermatogenesis
What are the functions of the blood-testis barrier?
- To separate sperm from the immune system preventing an immune response (anti-sperm abs & autoimmune orchitis)
- Selective transport of ions & small molecules to control the chemical environment for spermatogenesis
What happens in the proliferation phase of spermatogenesis?
1 - At puberty, prospermatogonia are reactivated and are then known as ‘As spermatogonia’
2 - As spermatogonia undergo mitosis in the basal compartment of the seminiferous tubule to produce another As spermatogonium (renewal) and an ‘A spermatogonium’
3 -The A spermatogonia undergo mitosis to produce B spermatogonia
4 - B spermatogonia undergo mitosis to produce primary spermatocytes
What happens in the division phase of spermatogenesis?
1 - The primary spermatocytes move from the basal compartment of the seminiferous tubule through the blood-testis barrier into the adluminal compartment
2 - Here, they undergo the first meiotic division over the course of 24 days to form diploid secondary spermatocytes
3 - They then undergo the second meiotic division over the course of 24 hours to form haploid round spermatids
What happens in the differentiation phase of spermatogenesis?
1 - Round spermatids elongate to form elongated spermatids & finally mature spermatozoa
2 - There is also the formation of specialised sperm structures: the acrosome, flagellum, mitochondria, nuclear and cytoplasm
Describe the structure of the specialised sperm acrosome.
- Formed from Golgi apparatus, which migrates & sits atop nucleus at the sperm head
- Contains hydrolytic enzymes for the acrosome reaction
- Receptor for fusion located on the inner acrosomal membrane
Describe the structure of the specialised sperm flagellum.
- Function is to facilitate sperm movement through the female tract & penetration of the egg vestments
- Forms from centrioles that migrate to the opposite end of the nucleus to the acrosome
- The distal centriole elongates to form the axoneme & the proximal centriole remains inside the sperm to form the spindle for the 1st mitotic division of the embryo (as eggs have no spindle fibres)
Describe the structure of the specialised sperm mitochondria.
The mitochondria in the sperm lie in a helical arrangement around the first part of the flagellum (the midpiece). These provide energy for motility
Describe the structure of the specialised sperm nucleus.
- The nucleus of the sperm is either X or Y bearing, and determines the sex of the embryo
- The DNA of the sperm is highly condensed as histone proteins are replaced with protamines
What is a residual body?
What happens to it after it forms?
- Superfluous cytoplasm forms a residual body (cytoplasmic droplet)
- This is phagocytosed by Sertoli cells
Which process occurs after spermatogenesis and what does this involve?
- Spermination
- The process by which sperm cells are released into the lumen of seminiferous tubules
What is the spermatogenic wave?
Different areas of a seminiferous tubule enter spermatogenesis at different times, which allows a continuous, rather than periodic, release of sperm
What are the hormone products of the testis?
1 - Androgens, mainly testosterone
2 - Oestrogens (small amount)
3 - Cytokines: inhibin & AMH
Into which substance is testosterone converted in the seminiferous tubules?
Which cells mediate this process?
Which enzyme is necessary to do this?
- Dihydrotestosterone
- Sertoli cells
- 5⍺-reductase
Which cells produce testosterone?
Leydig cells
What is the fate of dihydrotestosterone?
- Some binds to androgen receptors in Sertoli cells and stimulates spermatogenesis
- Some binds ABP (androgen binding protein) which is both a store and carrier of testosterone for transport in the testicular fluid
Which cells produce inhibin and what is its function?
- Sertoli cells
- It represses FSH production by the anterior pituitary
Which cells produce anti-Mullerian hormone (AMH) and what is its function?
- Sertoli cells
- It has an embryonic role in the development of the reproductive system
Where in the testis does LH bind and what is its effect?
- LH binds to LHCG receptors on Leydig cells
- It induces them to produce testosterone, which moves to the tubules and binds to the androgen receptor on Sertoli cells to induce spermatogenesis
Where in the testis does FSH bind and what is its effect?
- FSH receptor on Sertoli cells
- It induces the expression of the androgen receptor and stimulates the production of ABP and inhibin
What maturation processes must the sperm undergo after release from the testis and why?
- Spermatozoa leave the testis immobile and unable to recognise or bind to an egg
- The spermatozoa therefore need to undergo maturation in the male tract and capacitation in the female tract
What is the epididymis and what is its function?
- A single tube through which all sperm pass
- Most of the fluid the sperm are carried in is reabsorbed at this point, under the influence of oestrogen
- The epididymis plays an active role in sperm maturation, providing many molecules necessary for the sperm to acquire fertilising ability and motility (androgen-dependent)
What are the segments of the epididymis and what functions do they confer?
- Caput – sperm acquire motility
- Corpus – sperm acquire fertilising ability
- Cauda – sperm are stored
Into which structure do sperm pass after the epididymis?
What is the function of this structure?
- The vas deferens connects the epididymis to the ejaculatory duct
- It is densely packed with little fluid, and acts as a storage reservoir
Which structure is the target of vasectomies?
Vas deferens
What is semen?
Sperm + seminal plasma
Where is seminal plasma secreted from?
Seminal plasma is secreted by accessory sex glands (prostate & seminal vesicles)
What are the functions of seminal plasma?
1 - Transport
2 - Nutrition
3 - pH buffering (alkaline vs vaginal acidity)
4 - Provides antioxidants to maintain sperm DNA integrity
- STIs are also transferred in the fluid
What is semenogelin and what is its function?
A fibrinogen-like substance secreted by the seminal vesicles that causes clotting of the ejaculate within the upper vagina to allow time for the sperm to move into the cervix (action vs gravity)
What are the functions of the secretions from the prostate during copulation?
- Alkaline secretions high in zinc
- They contain enzymes for ejaculate clotting & liquefaction (the breakdown of the ejactulate clot after about half an hour of time within the vagina)
What is the function of the bulbourethral glands?
- Involved in the release of pre-ejaculate
- This serves in lubrication and neutralisation of acidic urine within the urethra
What occurs during capacitation?
- The motility of the flagellum changes from progressive to hyperactive
- The head of the sperm prepares for the acrosome reaction