The testis and spermatogenesis Flashcards
Structure of the Testes
Functions of the testis
•The testis has two main products: spermatozoa and hormones
- Manufacture of these products occurs in discrete compartments within the testes
- Production of spermatozoa is complex and highly orchestrated process
- A number of measurable parameters may correlate with the function of spermatozoa
The compartments of the testes
Seminiferous tubules within which spermatogenesis occurs. within the tubules, there is Vascularised stroma containing Leydig cells.
*The slide is a hematoxylin stain from of a biopsy of the testes and you can see the big circular structure which is a cross-section through a seminiferous tubule.
-upon the right-hand side, you can see adjacent seminiferous tubule. so the tubular structures are tightly packed together and ion between them is the stroma.
-within the stroma, you can see little blood vessels
-between the blood vessels are the Leydig cells
-the dot-like structure in the Leydig cells are the nuclei of cells and the pink (eosinophilic) stuff around the outside is the cytoplasm of the Leydig cell.
Hormones from the testis
- Most important hormones are androgens in maintaining reproductive and sexual function
- Testosterone synthesised from acetate and cholesterol by Leydig cells
- 4 – 10 mg testosterone secreted daily
- Secreted Principally into blood vessels but also lymph (and lymphatic transport to other structures probably important)
Hormones from the testis
- Some testosterone passes through to seminiferous tubules (lipid soluble)
- Converted to dihydrotestosterone by 5a-reductase in Sertoli cells
- Androgens are required for spermatogenesis
- The testis does not function in isolation…
Pituitary Control
- Production of androgens and spermatozoa related functionally
- At puberty, androgens rise and spermatogenesis commences
- Removal of pituitary (hypophysectomy) causes testes to shrink and spermatogenesis to arrest
- LH stimulates Leydig cells to produce androgens (which are required for spermatogenesis)
- FSH stimulates Sertoli cells and is required for spermatogenesis
The organisation of seminiferous tubules
- Each of them is about 30-80 cm long
- Total length is about 540m
- They each have Peripheral myoid cells surrounding each cell on the outside- the myoid cells have a contractile capability.
- Then they each have a layer of basement membrane which is so thin that we might not see it
- Inside the seminiferous tubule, there are Sertoli cells and spermatogenic cells.
Organisation of seminiferous tubules
- Physiological barrier formed by gap- and tight-junctioned complexes between Sertoli cells
- Creates a basal compartment and a separate adluminal compartment
- The Sertoli cells junction with each other, this means that on the inside there is a physiologically controlled compartment whereas on the outside , below the junctions, the cells are exposed to a seminiferous tubule.
- so there are 2 barriers (one outside of the physiological barrier and one inside the barrier) but all is still within the seminiferous tubule. but there are still gap and tight junction between the Sertoli cells
Process of Spermatogenesis can be divided into
1. Mitotic proliferation to produce lots of cells
2. Meiotic division to generate genetic diversity
3. Cell modelling to package chromosomes for delivery to the oocyte
–Large numbers of spermatozoa are produced
–300 to 600 per gram of testis per second are produced
Spermatogenesis
1 – mitosis
- The Germ cells of the immature testis called (prospermatogonia) are reactivated at the time of puberty to undergo rounds of mitosis in the basal compartment of the seminiferous tubule, towards the membrane.
- From this self regenerating population, emerge groups of cells called A spermatogonia which undergo a series of divisions to form a clone of cells.
- Finally after the last round of division, the clone divide to form resting primary spermatocytes which live in cavities formed in Sertoli cell cytoplasm.
- although nuclear division is completed, cytoplasmic division is not, so primary spermatocytes are linked by cytoplasmic bridges that hold these cells together.
Spermatogenesis: 2 - meiosis
- The Resting primary spermatocytes push through sertoli cell junctions into adluminal compartment
- Enter meiotic prophase
- Paired homologous chromosomes form contacts at pachytene, break, swap segments and rejoin
- Very sensitive to damage at this time
- First division ends with separation of homologous chromosomes to opposites ends of the meiotic spindle, cytoplasm divides forming short-lived secondary spermatocytes
- These quickly divide to form haploid spermatids.
Spermatogenesis explained by osmosis
perm production, or spermatogenesis, begins in puberty under the command of the hypothalamus.
The hypothalamus is a part of the brain that secretes gonadotropin-releasing hormone, or GnRH.
That GnRH travels to the nearby pituitary, which secretes two hormones of its own - luteinizing hormone, or LH, and follicle stimulating hormone, or FSH, that reach the gonads.
Before puberty, GnRH and, in turn, FSH and LH are secreted in low, constant amounts.
At puberty, secretion of these hormones intensifies and becomes pulsatile - sometimes more of the hormone is released, and sometimes less of the hormone is released.
LH binds to Leydig cells, and stimulates the production of testosterone, whereas FSH binds to Sertoli cells, making them produce androgen binding protein - or ABP, for short - which allows more testosterone to cross the blood-testis barrier and enter the seminiferous tubule.
So, it’s the increased concentrations of FSH, LH, testosterone that really gets spermatogenesis going.
Spermatogenesis starts with the spermatogonia, which are diploid cells - so they have 46 chromosomes, two of which are sex chromosomes, an X and a Y.
For diploid spermatogonia to form haploid gametes, that only have 23 chromosomes, they first undergo mitosis, and then undergo meiosis 1 and 2.
Following mitosis, a spermatogonium gives rise to two 46-chromosome daughter cells: one of them eventually becomes a primary spermatocyte, and the other one becomes a spermatogonium - this way the population of spermatogonia stays constant.
The primary spermatocyte slowly moves towards the lumen of the seminiferous tubule, passing between two Sertoli cells that nourish it.
The primary spermatocyte enters meiosis I, and emerges with 23 chromosomes each, one of which is either an X or a Y chromosome.
Secondary spermatocytes enter meiosis 2, which also have 23 chromosomes, but only one chromatid - so the right number of chromosomes and the proper amount of DNA.
Spermatids enter the lumen of the seminiferous tubule and undergo spermiogenesis - which is when they acquire a tail, and turn into sperm.
It takes roughly 2 months for spermatogonia to develop into sperm, and this process is regulated by various hormones.
Spermatogenesis: 3 - packaging
Cytoplasmic remodelling of the spermatid in order to form spermatozoa
5: There is a Tail for forward propulsion of the cell
4: There is a Midpiece area with mitochondria for energy
3: The chromosomes are very tightly packed in the Nucleus
2: The Cap region forms for sperm-oocyte fusion
1: Acrosome forms to penetrate oocyte
–During the course of that remodelling, the residual body is the remainder of the cytoplasm is formed and it is phagocytosed by the Sertoli cells.
Organisation of spermatogenesis
- Unlike ovulation, which is a regular but infrequent event, spermatogenesis is continuous.
- How is this complex process organised in space and time in the testes?
The spermatogenic cycle
- We considered generation of sperm from a single spermatogonium in a research.
- Once this process has started, new stem cells at the same location in a testis don’t start generation of clones again for a few days.
- The interval is constant at around 16 days, the process by which the stem cell population controls, or is controlled is unknown.
- The time for completion of spermatogenesis is 64 days, so there are four successive sets of clonal development (at four separate stages of the process) in one place at one time – and that’s what we see when we look down the microscope.
Cycle control
•If all spermatogonia were activated on 11th birthday, mature spermatozoa would be produced every 16 days.
•Result: episodic fertility
- whereas If the spermatogonia were activated randomly then continuous production could occur
- Infact, small regions seem to be activated together, in wedges and helices around the tubule
-so in the seminiferous tubules., we have a series of cells separated by a 16 days worth of growth and they could be different.
The spermatogenic wave
•If the seminiferous tubules are dissected longitudinally, adjacent synchronised clones of spermatogenesis are seen and this is described as spermatogenic wave.
The final stages of maturation of spermatozoa occur elsewhere
- Spermatozoa wash into the rete testis (net of testis)
- Through the vasa efferentia (afferent ductules)
- Into the epididymis where fluid is absorbed and sperm concentrated
- In the rete they can twitch: by the time they get to the cauda (tail) of epididymis they can swim
- The process is dependent on androgen stimulation
The components of semen
- Spermatozoa mixed with secretions from seminiferous tubules, epididymis etc.
- Addition of secretions from prostate, seminal vesicles and bulbourethral glands at time of ejaculation
-About 3 ml human
Cellular components inside semen
•Spermatozoa
•Epithelial cells released from tract
•Spermatogenic cells (primitive cells in the series of spermatogenesis)
•Leucocytes – risk of HIV etc .
What does the endocervix do?
- Secretes mucus with cyclical variation aliongisde the ovarian cycle.
- Macromolecular network of mucin fibrils with guiding spermatozoa
- Oestrogen stimulates watery mucus
- Progesterone inhibits secretory activity
- Sperm can penetrate the watery mucus from day 9, peak at time of ovulation
-The cervix is lined by columnar epithelium manufacturing mucin.
Capacitation
- Sperm recovered at ejaculation don’t fertilise ova in vitro immediately
- Those from the uterus will Have undergone capacitiation
- Stripping of glycoprotein from sperm surface which accumulates in the epididymis Causes hyperactive motility – ‘whiplash’
And make sperm responsive to signals from oocyte
