Structure
- The testis is made up of loops of seminiferous tubules, in the walls of which the spermatozoa are formed from the primitive germ cells
- Between the tubules are nests of Leydig cells, which secrete testosterone into the bloodstream
- Spermatic arteries in the testis are tortuous – the blood in the arteries runs parallel but in the opposite direction to the venous pampiniform plexus – this arrangement allows counter current exchange of heat and testosterone
Blood testis barrier
- Walls of the seminiferous tubules are lined by primitive germ cells and Sertoli cells, which are large glycogen containing cells stretching from basal lamina to lumen
- Germ cells must stay in contact with Sertoli cells to survive
- Tight junctions between Sertoli cells near the basal lamina form the blood-testis barrier
- This prevents larger molecules passing from the interstitium to lumen, or from basal part of tubule to luminal part of tubule
- However, steroids penetrate this barrier with ease, and some proteins also pass from Sertoli cells to Leydig cells, and vice versa, functioning in a paracrine manner
- Maturing germ cells also must pass the barrier as they move towards the lumen – this appears to occur without disruption of the barrier – via coordinated breakdown of the tight junctions above the germ cells and formation of new tight junctions beneath
- The fluid in the lumen of the seminiferous tubules is quite different to plasma:
- Contains very little glucose and protein
- Rich in androgens, oestrogens, K, inositol and glutamic and aspartic acids
- Composition maintained by blood-testis barrier
- The barrier also:
- Protects germ cells from noxious agents in the blood
- Prevents antigenic products of germ cell division and maturation entering circulation
- May help establish an osmotic gradient facilitating movement of fluid in tubular lumen
Spermatogenesis
The primitive germ cells next to the basal lamina of the seminiferous tubules are spermatogonia, which mature into primary spermatocytes beginning in adolescence.
The primary spermatocytes undergo meiotic division, to secondary spermatocytes then spermatids, which contain the haploid 23 chromosomes.
Spermatids mature into spermatozoa (sperm).
As a single spermatogonium divides and matures, its descendants remain tied together by cytoplasmic bridges until the late spermatid phase – this ensures synchrony of the differentiation of each clone of germ cells.
Its estimated one spermatogonium forms 512 spermatids, and a mature sperm takes about 74 days to form.
Each sperm is an intricate motile cell, rich in DNA:
- Its head is full of chromosomal material
- It wears a hat – the acrosome – which is a lysosome-like organelle rich in the enzymes which help with sperm penetration of the ovum
- The tail is wrapped in mitochrondria
- The membranes of late spermatids and spermatozoa contain a special form of ACE – germinal ACE (gACE) – function unknown
The spermatids mature into spermatozoa in the deep folds of the cytoplasm of the Sertoli cells:
- Mature sperm are then released from the Sertoli cells into the lumen
Sertoli cells secrete androgen-binding protein (ABP), inhibin and Mullerian inhibiting substance (MIS):
- Sertoli cells do not secrete androgens, but they do contain aromatase, which converts androgens to oestrogens
- And, they can produce oestrogens
- ABP probably acts to maintain a high androgen level in the tubular fluid
- Inhibin inhibits FSH
Whilst the stages of spermatogonia to spermatids seems androgen independent, the maturation from spermatids to spermatozoa depends on androgens acting on the Sertoli cell housing them
- FSH acts on the Sertoli cells to facilitate the last bits of spermatid maturation
- FSH also promotes ABP production
Further spermatozoa development
Spermatoza leaving the testis are not fully motile – they continue their maturation and develop their motility in their passage through the epididymis
- The ability to move forward (progressive motility) involves activation of a unique set of cation channels from the CatSper family, localised to the sperm tail
- CatSpers form an alkaline sensitive Ca channel which becomes more active as the sperm go from acidic vagina (pH 5) to cervical mucus (pH 8)
There is a suggestion of the sperm having olfactory receptors, and ovaries producing odorant like molecules, and these interact fostering movement of sperm towards towards ovary (chemotaxis).
The sperm move through uterus to isthmus of fallopian tubes – here they slow down and undergo capacitation
- This increases their motility and prepares them for the acrosomal reaction
- Once capacitated they move quickly to the tubal ampulla where fertilisation occurs
Effect of temperature
Spermatogenesis requires a cooler temperature cf. rest of body – the testes are normally maintained about 32 degrees.
They are kept cool by air circulating the scrotum, and probably from heat exchange due to the counter current mechanism between arteries and veins.
Situations which increase temperature (cryptorchidism, hot baths, ‘insulated athletic supporters’) can reduce sperm counts in some cases up to 90 %
Suggestion of seasonal effect, with higher sperm counts in the winter.
Semen
Contains sperm and secretions from prostate, seminal vesicles, bulbourethral glands and probably urethral glands.
Average volume 2.5 – 3.5 mL after several days of abstinence (volume of semen and sperm count decrease rapidly with repeated ejaculation). Semen pH is 7.35 – 7.50.
Each mL contains about 100 million sperm (< 20 % abnormal forms normally)
50 % of men with 20 – 40 million/mL sperm will be infertile, and essentially all men with < 20 million/mL will be infertile.
Morphologically abnormal or immotile sperm also associated with infertility.
Prostaglandins formed in the seminal vesicles are found abundantly in semen, but their function isn’t really known.
Human sperm move at 3 mm / minute through female genital tract, reaching tubes 30 – 60 minutes after sex, possibly aided by contractions in the female organs.
Endocrine control
The hypothalamus has pulsatile secretion of GnRH which causes the cyclical secretion of pituitary and gonadal hormones.
- Hypothalamus is anatomically linked to pituitary with both neural and portal vascular pathways (thus avoiding systemic circulation)
- GnRH (LHRH) has a half-life of 5 – 7 minutes and is almost entirely removed during first pass through pituitary where is stimulates FSH and LH release
GnRH/LHRH:
- Opioids reduce GnRH secretion
- FSH, LH, testosterone also reduce GnRH secretion
- Prostaglandins can increase GnRH release
FSH:
- Acts on Sertoli cells.
- FSH and androgens maintain spermatogenesis in the testis
- Also stimulates secretion of ABP and inhibin
LH:
- Acts on Leydig cells
- Stimulates secretion of testosterone – which causes negative feedback on LH secretion
Testosterone:
- Released by Leydig cells in response to LH
- Testosterone then reduces plasma LH
- Has no effect on FSH except in very large doses.
- Bathes the seminiferous tubules providing the high local concentration of androgens needed for spermatogenesis
- Systemically administered testosterone does not raise the androgen level in the testes much, and significantly reduces systemic LH release
- Consequently, systemic testosterone will generally reduce sperm count
- Testosterone was suggested as a contraceptive, but the dose needed to suppress spermatogenesis causes sodium and water retention
Inhibin:
- Released by Sertoli cells, it inhibits FSH secretion
Prolactin:
- Prolactin inhibits the effect of gonadotropins
- Excess prolactin causes ED in men
Pituitary insufficiency / hypopituitarism
- Testes and ovaries become atrophic
- Adrenal cortex atrophies and secretion of cortisol and sex hormones falls
- Stress induced increases in aldosterone are absent, but normal basal aldosterone and increases in response to salt are normal for some time
- Sexual cycles stop, and some secondary sex characteristics regress
- Become more sensitive to insulin