A growing body of information now supports the theory that oestrogen replacement therapy can substantially eliminate or attenuate the complications incurred as a result of the menopause. In particular, data support the claim that oestrogen replacement therapy for postmenopausal women is associated with the relief of vasomotor symptoms, the prevention of osteoporosis and urogenital atrophy, a lowering of cardiovascular morbidity and mortality, improved cognitive functioning, and a lower incidence of Alzheimer's disease.

In summary, apoptosis is an important concept in understanding many facets of human reproduction. Recent advances in the understanding of molecular mechanisms of apoptosis will allow us to understand this physiologically important process. How can the modulation of this process be applied to human reproduction? Studies to further understand the abnormalities of apoptosis, either too much or too little, may lead to a better understanding of the clinical problems in human reproduction.

We summarize future directions towards further understanding the roles of apoptotic processes in human reproduction in Table 3. The diseases listed in Table 3 are problems which could be approached from the apoptosis point of view. With further study using this concept as the lens, new diagnostic tools or therapies may be developed for these problems.

Approximately one in ten couples experience infertility, and in about 40% of these infertile unions there are abnormalities in the fertility of the male partner. The clinical management of these infertile men is less than satisfactory because in 40% of such patients the cause of the abnormalities of sperm production and quality is unknown. The possibility that genetic disorders may account for a proportion of these disturbances of sperm production has been raised. It is well recognized that chromosomal abnormalities such as Klinefelter's syndrome cause azoospermia and that gene defects are the basis of testicular feminization, Kallman's syndrome and Reifenstein's syndrome. With the explosion in our knowledge of the human genome, the possibility exists that other genetic disorders may form the basis of other sperma-togenic abnormalities. The past decade has witnessed the accumulation of evidence linking abnormalities of the Y chromosome with disturbances in sperm production and these observations form the basis of this review.

Spermatogenesis in mammalian species begins after birth. The gonocytes, arrested at G2 of the cell cycle in the foetus, resume mitotic proliferation after birth. As identified in the mouse, the gonocytes migrate towards the periphery of the seminiferous cords at day 4 to day 6 after birth and are located in close contact with the basal lamina. From this stage the gonocytes are referred to as primitive type A spermatogonia. These cells continue mitotic proliferation and differentiate to form type B spermatogonia. By day 10 after birth, many of the type B spermatogonia have formed preleptotene primary spermatocytes which undergo a final phase of DNA synthesis (leptotene) prior to entering meiotic prophase (zygotene).