THE ETHANE DIMETHANESULFONATE-INDUCED DECREASE IN THE FERTILIZING ABILITY OF CAUDA EPIDIDYMAL SPERM IS INDEPENDENT OF THE TESTIS

Several decades ago it was reported that when adult male rats were exp osed to a single injection of 50 mg/kg body weight ethane dimethanesul fonate (EDS) and mated with untreated females, average litter size was significantly reduced as early as 2 weeks later. Recently, we demonst rated that EDS exerts multiple effects in the epididymis of adult rats . Some of these effects were independent of reduced serum testosterone (T) levels. Later we found that EDS has direct effects on epididymal epithelial cells in vitro. Herein, we sought to determine whether EDS perturbs the fertilizing ability of cauda epididymal sperm. Four days after exposure to 50 mg/kg EDS, sperm from the proximal cauda epididym idis were inseminated into adult receptive females in utero; on the ne xt day the percentage of fertilized eggs was determined. Exogenous T a dministration and castration were used to determine what role, if any, androgen deprivation and the testis had on the fertilizing ability of proximal cauda epididymal sperm. Sperm motion parameters, serum T, T in the caput/corpus epididymidis, and detergent-extracted sperm protei n were evaluated and correlated with fertilizing ability. We found tha t both castration and EDS exposure significantly compromised the ferti lizing ability of sperm in proximal cauda epididymidis 4 days after ex posure. Exogenous T, sufficient to maintain serum T, completely restor ed the fertilizing ability of sperm following castration, but not afte r EDS exposure. Moreover, exogenous T failed to restore fertilizing ab ility when castrated animals were exposed to EDS. Thus, the effects th at EDS exerts on sperm maturation in vivo are independent of the testi s. Finally, the only endpoint that was well correlated with fertilizin g ability was the relative amount of an acidic 18-kDa sperm protein.