Ethanol-induced male reproductive tract pathology as a function of ethanol dose and duration of exposure

Chronic ethanol ingestion by the male results in several manifestations of reproductive dysfunction. However, little is known concerning 1) the level of ethanol or duration of ethanol exposure necessary to produce pathological changes in the male reproductive tract; or 2) mechanism(s) by which ethanol exerts its toxic effects. The purpose of the present study was to develop an animal model which describes ethanol-induced male reproductive failure and to define conditions of ethanol exposure which alter male reproductive tract function. Proven breeder male C57Bl/6J mice were maintained on either a 5% (v/v) ethanol liquid diet for periods of 5, 10 or 20 weeks or a 6% (v/v) ethanol diet for 5 weeks. Daily blood ethanol levels peaked at 125 to 200 and 268 mg/100 ml in animals consuming the 5 and 6% ethanol diets, respectively. Plasma testosterone levels were depressed throughout all treatments, an effect which appeared reversible. Plasma testosterone was poorly correlated (r = 0.28) with blood ethanol levels during treatment. After treatment, reproductive tract pathology included reduced testicular and accessory sex organ weights, decreased spermatogenesis, increased desquamation of immature germ cells into the seminiferous tubule lumina and increased frequency of inactive seminiferous tubules. Whereas minimal changes were noted after 5 weeks treatment with the 5% ethanol diet, deficiencies became increasingly evident after either longer exposure periods or treatment with 6% ethanol for the same period. None of the treatment regimens resulted in altered plasma levels of hepatic enzyme markers or in altered histological appearance. The data indicate that male reproductive function is sensitive to both ethanol dose and duration of exposure. The animal model described in the present study should have utility in the evaluation of putative mechanisms of ethanol-induced male reproductive dysfunction.