T2 L9 The Short but happy life of a sperm Flashcards
What are the functions of the testes?
Production of spermatozoa and hormones
These occur in discrete compartments
Production of spermatozoa is complex and highly orchestrated process
A number of measurable parameters may correlate with the function of spermatozoa
What are the compartments of the testis?
Seminiferous tubules within which spermatogenesis occurs
Vascularised stroma containing Leydig cells
What hormones are released from the testes?
- Most important hormones are androgens in maintaining reproductive and sexual function. Androgens are required for spermatogenesis.
- Testosterone synthesised from acetate and cholesterol by Leydig cells
How much testosterone is secreted daily in a mature male?
4 – 10 mg testosterone secreted daily
Mainly into blood vessels but also lymph (and lymphatic transport to other structures probably important)
What is testosterone converted to and where does this conversion take place?
Converted to dihydrotestosterone by 5a-reductase
In the Sertoli cells
Where does some of the testosterone end up in?
Seminiferous tubules
How does the pituitary gland control hormone production in the testes?
- LH acts on the Leydig cell to produce testosterone
- FSH acts on the Sertoli cells to start spermatogenesis
NOTE: Testosterone is needed for spermatogenesis to occur.
Describe the structure of the seminiferous tubules
Surrounded by myoid cells (these cells have a slight capacity to contract).
Then a layer of basement membrane
Sertoli cells and spermatogenic cells within the tubules
Physiological barrier formed by gap- and tight-junctioned complexes between Sertoli cells. Creates a basal compartment containing spermatogonia, whilst spermatocytes, spermatids and spermatazoa are in a separate adluminal compartment
What are the 3 acts of spermatogenesis?
- Mitotic proliferation to produce lots of cells
- Meiotic division to generate genetic diversity
- Cell modelling to package chromosomes for delivery to the oocyte
How much spermatozoa is produced per second?
300 to 600 per gram of testis per second
What is the 1st stage of spermatogenesis? Describe what happens
MITOSIS
Germ cells of immature testis (prospermatogonia) are reactivated at puberty to undergo rounds of mitosis in the basal compartment of the tubule
A1 spermatogonia comes from this population, 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
Within this mitotic phase of division, although nuclear division is completed, cytoplasmic division is not, so all of the primary spermatocytes resulting from the division of a spermatogonium are linked by cytoplasmic bridges
What is the 2nd stage of spermatogenesis? Describe what happens
MEIOSIS
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
What is the 3rd stage of spermatogenesis? Describe what happens
CYTOPLASMIC REMODELLING OF SPERMATID
1: Acrosome forms to penetrate oocyte
A small residual body is the dustbin for unwanted cytoplasm, later eaten by sertoli cell
2: Cap region forms for sperm-oocyte fusion
3: Nucleus with packaged chromosomes
4: Midpiece with mitochondria for energy
5: Tail for forward propulsion
How does spermatogenesis compare to ovulation?
Unlike ovulation which is periodical, spermatogenesis is a continuous process
How long does the spermatogenic cycle last for?
Once spermatogenesis has started, new stem cells at the same location 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. Mature spermatozoa is produced every 16 days.
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
Where does a single generation of sperm originate from?
A spermatogonium
What would happen is spermatogonia were activated randomly?
Continuous production would occur
What is a spermatogenic wave?
A spermatogenic cycle is defined as the time it takes for the reappearance of the same stage within a given segment of the tubule.
Each stage of the cycle follows in an orderly sequence along the length of the tubule.
The distance between the same stage is called the SPERMATOGENIC WAVE. If the seminiferous tubules are dissected longitudinally, adjacent synchronised clones of spermatogenesis are seen
What happens in the final stages of spermatozoa maturation and where does it occur?
Spermatozoa wash into the rete through the vasa efferentia into the epididymis where fluid is absorbed and sperm concentrated.
In the rete they can twitch, by the cauda epididymis they can swim
The process is dependent on androgen stimulation
What are the fluid and cellular components of semen?
FLUID
- From seminiferous tubules, epididymis. Addition of secretions from prostate, seminal vesicles and bulbourethral glands at time of ejaculation
- Nutrition (fructose, sorbitol)
- Buffer (to protect against vaginal acidity)
- Antioxidants (ascorbic acid, hypotaurine)
- About 3 ml in the male
CELLULAR
- Spermatozoa
- Epithelial cells from tract
- Spermatogenic cells
- Leucocytes – risk of HIV etc
What is the function of the endocervix?
Secretes mucus with cyclical variation
Macromolecular network of mucin fibrils. Scientists are unsure whether it guides the spermatozoa
Oestrogen stimulates watery mucus
Progesterone inhibits secretory activity
When can sperm penetrate the endocervix?
From day 9
Peaks at time of ovulation (around day 12)
What does the endocervix offer sperm?
Receptive to sperm at time of ovulation, interference at other times
Protection from hostile vagina, and from being phagocytosed
Supplementation of energy requirements
Sperm selection by differential motility and morphology
Short term reservoir within endocervical crypts
Initiation of the next stage in sperm maturation: ‘capacitiation’
What occurs during capacitation?
Glycoprotein from sperm surface is stripped which accumulates in the epididymis
Causes hyperactive motility – ‘whiplash’
This makes the sperm responsive to signals from oocyte
How is cervical mucus tested?
Consistency (watery or viscous)
Spinnbarkeit (means elasticity, stickiness)
Ferning (crystalisation on a glass surface)
NOTE: These are crude assessments of a complex physiological situation. Detailed testing can follow
E.g. Looking at spermatozoa penetrating mucus and assessing their motility
How is semen specimen obtained?
Via masturbation
NOTE: Condoms contain spermicide
How much (in terms of volume) is normally ejaculated?
Normal ejaculated volume is 1.5 – 6 ml
Why may the volume differ from the values quoted in the previous question?
Volume may be low in retrograde ejaculation (entry of semen into the bladder instead of going out through the urethra during ejaculation)
High volume may reflect abstinence or accessory gland inflammation
What is the WHO (2016) cut-off for semen volume?
1.5 ml
Define sperm concentration (or density)
The number of sperm per ml in the total ejaculate
What is a normal sperm concentration?
> 15 million per ml
What % of the spermatozoa has to be alive for the semen to be vital?
58% or more
Define motility
Percentage of progressively motile sperm in the ejaculate
Progressively motile means they go somewhere, rather than swim around in circles
What is the WHO cut off for the lower limit of normal for progressive motility?
32%
NOTE: There is variation in repeat samples from individuals and poor correlation with fertility
How is the morphology of the sperm determined?
Via visual assessment
Greater than 4% normal forms acceptable (WHO 2010)
Other more stringent criteria exist
Define NORMOZOOSPERMIA
Normal values
Define OLIGOZOOSPERMIA
Low concentration
Define ASTHENOZOOSPERMIA
Too little motility
Define TERATOZOOSPERMIA
Too many abnormals
Define OLIGOASTHENOTERATOZOOSPERMIA
Mixture of oligozoospermia, asthenozoospermia, teratozoospermia
Define AZOOSPERMIA
No spermatozoa
Define ASPERMIA
No ejaculation
