Molecular biology of sperm maturation in the human epididymis

Male infertility is a frequent cause of childlessness, and, indeed, a comparison of the contributions to conception failure made by male and female factors shows them to be equally frequent. In practice, male infertility appears to be resistant to most treatments. However, the major reason for this may be that often attempts are carried out without knowing the cause of the problem. Unlike in women, obstructions and hormonal disorders are rare in male infertility. Rather, it would appear that sperm disorders are the most common cause, reflecting a variety of pathogenetic mechanisms. Defects in sperm morphology, defective sperm movement, deficient development or functional failure of the acrosome, and the excessive generation of reactive oxygen species are changes that are often seen in infertile semen, but little is known about their aetiology. In 5–10% of men being treated for infertilty, an autoimmune reaction against spermatozoa is observed. Although the correlation between the presence of systemic antisperm antibodies and fertility potential is poor, the appearance of sperm-bound antibodies of immunoglobulin class IgA in semen seems to be closely associated with infertility. Studies in laboratory animals and humans have shown that complementary adhesion molecules are located on the surface of oocytes and spermatozoa. These molecules interact and lead to gamete fusion. Abnormalities in these molecules on the sperm surface might be expected to contribute to male infertility. However, their clinical significance has not yet been documented, and the molecular basis of human gamete interaction is far from being understood. Therefore, the key to understanding male infertility may lie in basic research which directly targets the fundamental cellular and molecular biology of the human spermatozoon.