L9 + 10 The short but happy life of a sperm Flashcards
Function of the testis
The testis has 2 main products: spermatozoa and hormones
Manufacture of these products occurs in discreet compartments
Production of spermatozoa is complex
A number of measurable parameters may correlate with the function of spermatozoa
Compartments of the testis
Seminiferous tubules within which spermatogenesis occurs
Vascularised storm containing Leydig cells
Where and what is testosterone synthesised by?
From acetate and cholesterol by Leydig cells
How much testosterone is secreted daily?
4-10mg
Where is testosterone secreted into?
Principally into blood vessels but also lymph (and lymphatic transport to other structures probably important)
What does some testosterone pass through?
Seminiferous tubules (lipid soluble)
What is testosterone converted into?
dihydrotestosterone by 5a-reductase in Sertoli cells
What are androgens required for?
Spermatogenesis
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
FSH stimulates Sertoli cells and is required for spermatogenesis
Seminiferous tubules
Surrounded by myoid cells
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
This creates a basal compartment containing spermatogonia, whilst spermatocytes, spermatids and spermatozoa are in separate adluminal compartment
Spermatogenesis in 3 acts
3 elements:
- Mitotic proliferation to produce lots of cells
- Meiotic division to generate genetic diversity
- Cell modelling to package chromosomes for delivery to the oocyte
Large number of spermatozoa are produced
300-600 per gram of testis per second
Spermatogenesis 1 - mitosis
Germ cells of immature testis (prospermatogonia) are reactivated at puberty to undergo rounds of mitosis in the basal compartment of the tubule
From this self regenerating population emerge groups of cells called A1 spermatogonia which undergo a series of divisions to form a clone of cells
Finally after the last round of division, the clone divides 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
Spermatogenesis 2 - 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
Spermatogenesis 3 - packaging
Cytoplasmic remodelling of spermatid
Tail for forward propulsion
Midpiece with mitochondria for energy
Nucleus with packaged chromosomes
Cap region forms for sperm-oocyte fusion
Acrosome forms to penetrate oocyte
- a small residual body is the dustbin for unwanted cytoplasm, later eaten by sertoli cell
Organisation of spermatogenesis
Unlike ovulation, which is regular but infrequent event, spermatogenesis is continuous
The spermatogenic cycle
We considered generation of sperm from a single spermatogonium
Once this process 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
The time for completion of spermatogenesis is 64 days, so there are 4 successive sets of clonal development (at 4 staged of the process) in one place at one time
Cycle control
If all spermatogonia were activated on 11th birthday, mature spermatozoa would be produced every 16 days
Result: episodic fertility
If the spermatogonia were activated randomly then continuous production could occur
In fact, small regions seem to be activated together, in wedges around the tubule
The spermatogenic wave
If the seminiferous tubules are dissected longitudinally, adjacent synchronised clones of spermatogenesis are seen
The final stages of maturation of spermatozoa occur elsewhere
Spermatozoa wash into the rate
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
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 3ml in the male
- half a litre in the boar
Cellular components
Spermatozoa
Epithelial cells from tract
Spermatogenic cells
Leucocytes - risk of HIV etc
Fluid components
Can’t be essential for fertilisation
Provide a fluid vehicle for spermatozoa
- nutrition (fructose, sorbitol)
- buffer (to protect against vaginal acidity)
- antioxidants (absorb acid, hypotaurine)
What does the endocervix do?
Secretes mucus with cyclical variation
Macromolecular network of mucin fibrils? guiding spermatozoa
Oestrogen stimulates watery mucus
Progesterone inhibits secretory activity
Spem can penetrate from day 9, peak at time of ovulation
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: ‘capacitation’
Capacitation
Sperm recovered at ejaculation don’t fertilise ova in vitro immediately
Those from the uterus will have undergone capacitation
Stripping of glycoprotein from sperm surface which accumulates in the epididymis
Causes hyperactive motility - ‘whiplash’
And make sperm responsive to signals from oocyte where we end our journey
3 properties of cervical mucus
Consistency (watery or viscous)
Spinnbarkeit (means elasticity, stickiness)
Ferning (crystallisation on a glass surface)
Testing cervical mucus
These are crude assessments of a complex physiological situation
Detailed testing can follow
e.g. looking at spermatozoa penetrating mucus and assessing their motility
Measuring sperm
A number of variables may be evaluated through analysis of semen
These may correlate with fertility with varying degrees; some evidence is controversial
Specimen is obtained by masturbation, collected in a clean container - (condoms often contain spermicide)
Volume of sperm
Normal ejaculated volume is 1.5 - 6ml
Volume may be low in retrograde ejaculation, high volume may reflect abstinence or accessory gland inflammation
1.5ml is the cut off(WHO 2010)
Concentration and vitality
Sperm concentration, or density, defined as the number of sperm per ml in the total ejaculate
Normal is over 15 million per ml
Vitality: 58% or more live spermatozoa
Motility of sperm
Defined as percentage of progressively motile sperm in the ejaculate
Progressively motile means they go somewhere, rather than swim around in circles
WHO uses 32% as the cut off for the lower limit of normal progressive motility
Variation in repeat samples from individuals and poor correlation with fertility
Morphology of sperm
Visual assessment of sperm
Greater than 4% normal forms acceptable (WHO 2010)
Other more stringent criteria exist
Normozoospermia
normal values
Oligozoospermia
low concentration
Athenozoospermia
too little motility
Teratozoospermia
too many abnormals
Oligoasthernoterto-zoospermia
mixture of the three
Azoospermia
no spermatozoa
Aspermia
no ejaculate
