Each testis contains several thousand convoluted seminiferous tubules. Sperm are made within these tubules, while testosterone hormone is made between them, from nests of cells called the interstitial cells of Leydig.

The seminiferous tubules are lined by small cells known as spermatogonia. From puberty onwards, these start to divide to produce the cells which will develop into sperm. Alternating with the spermatogonia are much larger cells, the Sertoli cells, which have three important functions:

1. They form a tight barrier between the tubules and other tissues ­ the blood-testis barrier.

2. They secrete nutrient fluids into the tubules.

3. They act as 'nursery units' for developing sperm.

THE BLOOD-TESTIS BARRIER

The Sertoli cells are tightly connected to each other, to the spermatogonia and to the basement membrane of the seminiferous tubule to form the blood-testis barrier.

Rather like a rubber ground sheet, this interlocking barrier prevents large molecules seeping to and fro between the central space of the seminiferous tubules and surrounding tissues, including the bloodstream.

Figure 7: Sertoli cells interlocking to form the blood­testis barrier. Spermatogonia divide so that spermatocytes have to pass up through the blood­testis barrier

At puberty, the presence of follicle stimulating hormone (FSH) and increased levels of testosterone act rather like a turbo charge, boosting the Sertoli cells into action. Testo-sterone is fat-soluble and can easily diffuse through the Sertoli cell membrane. Once inside, it binds to an androgen receptor and is taken to the cell nucleus where it 'switches on' certain genes.

Sertoli cells start to pump salts and nutrients in different directions across the tubular walls. They also secrete an androgen-binding protein into the tubule which mops up testosterone and keeps it at a high local concentration around the developing sperm.

Due to the secretory actions of the Sertoli cells, fluid found within the tubules is very different from that outside. It is rich in testosterone, potassium and the amino acids, aspartic acid and glutamic acid, which are all needed for sperm development.

The blood-testis barrier is important for maintaining these different concentrations of substances within the tubules. Surprisingly, Sertoli cells can pump fluid into the tubular space (lumen) against quite a high pressure. If a blockage prevents fluid flowing from the tubules into the epididymis, secretion still continues, so the tubules blow up to the point where the blood supply is cut off. This can lead to pressure damage, shrinkage and even the death of tubular cells.

Perhaps the most important function of the blood- testis barrier is that it prevents sperm fragments formed during development from accidentally entering the circulation and triggering the formation of anti- sperm antibodies. It also protects young sperm from attack by blood-borne infections or poisonous molecules. If the barrier is disrupted, for example by injury or vasectomy, so that sperm and blood can mix, the sperm are often misinterpreted as foreign by the immune system. Anti-sperm antibodies are made and this can obviously result in subfertility.

SPERMATOGENESIS

Spermatogenesis is a complex process, involving the constant proliferation of parent cells (spermatogonia) to form the basic stock, the primary spermatocytes. These possess a full set of genes, identical to those in other body cells. The primary spermatocytes then undergo a specialized division (meiosis) in which they split twice to form a generation of cells with a random half set of genes ­ the spermatids. These develop and mature to produce mature, motile sperm.

Interestingly, when the spermatogonia divide, the resultant cells must pass through the blood-testis barrier as they mature and travel towards the tubular lumen. This seems to occur without disrupting the barrier. Adjacent Sertoli cells form new tight junctions below the moving spermatocytes and spermatids while, at the same time, releasing the connections above.

Meiosis

Each normal body cell contains a set of genes arranged on 46 chromosomes within the nucleus. These chromosomes are arranged in 23 pairs.

The specialized process which splits a spermatocyte with a full set of genes (46 chromosomes) into the spermatids with only a half set of genes (23 chromosomes) is a two-stage process called meiosis.

During the first stage, the chromosomes within the sper- matocyte nucleus double up (to 92 chromosomes) and then pair off (Figure 8). The chromosomes exchange random blocks of genes within each pair. This is nature's way of shuffling the gene pool and introducing variation within the offspring. After exchanging genetic material, the paired chromosomes separate and the spermatocytes divide again. Each parent primary spermatocyte has now produced two secondary spermatocytes which contain a different mix of genes, arranged in a different order, on their 46 (23 pairs) of chromosomes.

The second stage of meiosis now starts. The 23 pairs of chromosomes within each nucleus split up, the nuclear membrane disintegrates, and one chromosome from each pair migrates to opposite ends of the cell. The spermatocytes divide again ­ but this time, each new cell only takes one of each pair of chromosomes. As a result, each new cell, a spermatid, only contains a half set of 23 chromosomes, whereas all other body cells contain 46.

As a result of meiosis, each original primary spermatocyte has divided into four spermatids, each containing only half the genetic material found in the original primary spermatocyte. More importantly, each spermatid contains a unique set of genes ­ a random half selection from its parent cell. Some spermatids may have a similar selection of genes to other spermatids (accounting for family similarities between future brothers and sisters), but the chances of any two being identical are virtually zero.

Figure 8: Meiosis

Spermatids

The spermatids look nothing like the sperm they will develop into over the next 70-odd days. They rapidly move towards the nearest Sertoli cell and bury their heads within it, rather like ostriches with their heads in the sand.

Sertoli cells contain a high concentration of a carbohydrate storage compound, glycogen, which supplies energy to the developing sperm. They also secrete a number of hormones, proteins, sugars and other nutrients that help its lodgers to mature.

Figure 9: Spermatogonia, spermatocytes, spermatids and Sertoli Cells

The spermatids start to grow a tail for forward propulsion, a thickened mid-piece full of mitochondria (energy factories ­ see mitochondria), and a sac of enzymes at their front end (acrosome). These enzymes are necessary for cutting into the egg shell at fertilization. As the tail of each spermatid lengthens, it projects into the central bore of the tubule, waving in the eddy currents rather like tiny hairs.

As the spermatids mature, they are slowly pushed towards the surface of the Sertoli cell. Once their tails are sufficiently developed, the sperm are ejected into the lumen of the seminiferous tubule, although they are not yet fully mobile.

The rate of secretion of fluid into the tubules by the Sertoli cells is so great that a current is set up. This washes unat-tached sperm through the tubules towards the epididymis. Here, some fluid is reabsorbed so the sperm are concentrated from an initial 50 million sperm per ml on entering the epididymis to around 5,000 million per ml on leaving it.

While passing through the epididymis, proteins are added to the outer membrane of the sperm, they finish maturing and dramatically change in behaviour. On entering the epididymis, sperm are incapable of more than the odd twitch of movement, and if harvested are incapable of fertilizing an egg. After passing through the 6 m (18 ft) of epididymis, however, sperm are fully mobile and capable of both attaching to an egg and penetrating its outer coat. From the epididymis, sperm pass up into the top of the vas deferens where they are stored while completing their development. They are tightly packed together and are moved along by muscular contractions of the vas deferens walls.

Altogether, it takes around 100 days to make a sperm from start to finish:

• 74 days from division of the spermatogonium to the production of a semi-motile sperm

• 20 days for the sperm to traverse the 6-m (18-ft) length of the tortuous epididymis while they gain their motility

• at least six days storage within the vas deferens before ejaculation.

Spermatozoa

Spermatozoa (singular: spermatozoon) are one of the most specialized cells in the body. There are normally between 66 and 100 million sperm per ml of semen, with an average of 300 million sperm per ejaculation. This figure can rise to over 1,000 million spermatozoa in any one ejaculate.

Each sperm measures 0.05 mm (1Ž500 in) in length and has a so-called 'head', 'neck' and 'tail'.

The Sperm Head

Shaped like a flattened tear drop. The front 'snout' contains a sac of enzymes, called the acrosome. These enzymes are essential for fertilization and help the sperm dissolve the coating of an egg to allow penetration.

Figure 10: A Spermatozoon

Behind the acrosome is the cell nucleus, containing a random half set of a man's genetic material (DNA) tightly coiled within 23 chromosomes.

Each sperm possesses a unique set of genetic information which, although it may be similar to the genetic information in another sperm from the same male, will never be exactly the same.

The Neck

A fibrous area where the middle piece of the sperm tail joins the head. The neck is flexible and allows the head to swing from side to side as part of the swimming movement.

The Tail

The sperm tail is made up of 20 long filaments ­ a central pair surrounded by two rings containing nine fibrils each. At the front end of the tail are a further ring of outer dense fibres and also a protective tail sheath. The tail is divided into three sections: the middle piece, principal piece and end piece. The middle piece is the fattest part of the tail. Its extra thickness is due to an additional spiral layer wrapped round the tail which is full of mitochondria ­ the power units ­ which provide energy for sperm motility. These use the two sugars, glucose and fructose, as fuel to produce energy.

The principal piece consists of the 20 filaments plus the outer dense fibres and tail sheath. At the end piece, the dense fibres and the tail sheath peter out until only a thin cell membrane encloses the end piece of the tail. This gradual thinning and tapering of the tail is what produces the sperms' characteristic whiplash-like swimming motion.