The Amoroso Lecture - The human spermatozoon - a cell in crisis?

A great deal of evidence has accumulated in recent years to suggest that th ere has been a gradual increase in male reproductive pathology over the pas t 30-40 years, as evidenced by increased rates of testicular cancer and dec lining semen quality. The hypothesis is advanced that this phenomenon is ca usally related to the ability of male germ cells to generate reactive oxyge n metabolites. When produced in low levels, such metabolites are thought to enhance sperm function by stimulating DNA compaction and promoting a redox -regulated cAMP-mediated pathway that is central to the induction of sperm capacitation. When produced in excessive amounts, the same metabolites stim ulate DNA fragmentation and a loss of sperm function associated with peroxi dative damage to the sperm plasma membrane. Free radical-induced mutations in the male germ line may also be involved in the aetiology of childhood ca ncer and recent increases in the incidence of seminoma. Ln light of these c onsiderations, establishing the mechanisms for free radical generation by t he male germ line and determining the factors that influence this activity are important objectives for future research in this area.