Xenobiotic metabolism, genetic polymorphisms and male infertility

Male reproductive function may be impaired by various occupational and envi ronmental chemical agents. The majority of these xenobiotics, however, requ ire metabolic activation in order to exert adverse effects via covalent int eractions between intermediate metabolites and cellular macromolecules such as DNA or protein. In addition, metabolization may alter endocrine-disrupt ing properties of xenobiotics. Thus tissue-specific expression and regulati on of multiple xenobiotic-metabolizing enzymes are likely to play an import ant role in chemically induced disorders of male reproductive organs. Recen t studies suggest that genetic polymorphisms underlying inter-individual an d inter-ethnic variability of xenobiotic metabolism modulate susceptibility to male reproductive disorders. For cytochrome P450 1A1 (CYP1A1), a key en zyme In extra-hepatic metabolic activation of lipophilic xenobiotics, incre ased frequencies of two genetically linked polymorphisms have been found am ong infertile men.