CHLOROETHYLMETHANESULFONATE-INDUCED EFFECTS ON THE EPIDIDYMIS SEEM UNRELATED TO ALTERED LEYDIG-CELL FUNCTION

Decades ago it was reported that when male rats were exposed to chloro ethylmethanesulfonate (CEMS) for 5 days prior to weekly matings with u ntreated females, the second mating resulted in reduced litter size. S ince fertility was not assessed at earlier time points, it was not pos sible to determine whether CEMS exerted any effects on sperm in the ep ididymis. In this study, we used a 4-day exposure and assessed multipl e reproductive endpoints on Day 5 to characterize effects of CEMS expo sure (6.25-25 mg/kg) on Leydig cells and the epididymis. Exposure to C EMS caused a dose-related decline in serum testosterone (T) levels. Th is occurred at a dose lower than that required to decrease T productio n in vitro by testicular parenchyma. The in vitro decline was not attr ibuted to a decrease in maximal hCG-stimulated T production, but to a decrease in unstimulated T production. CEMS was 5-fold less sensitive than ethane dimethanesulfonate (EDS) in reducing maximal hCG-stimulate d T production. To control for alterations in the epididymis resulting from decreased serum T alone, T was implanted in CEMS-treated animals to maintain serum T at a concentration similar to that found in norma l rats. This exogenous T failed to prevent the CEMS-induced decrease i n the weight of the caput/corpus epididymidis but did prevent the CEMS -induced decrease in seminal vesicle weight. Implantation of T failed to prevent the CEMS-induced reduction in sperm reserves in the cauda e pididymidis, and it failed to prevent the CEMS-induced alterations in the histology of both the corpus and proximal cauda epididymidis. The height of the epithelium in both of these regions was increased, and c lear cells disappeared from the proximal cauda epididymidis. These res ults demonstrate that CEMS might alter the ability of the Leydig cell to respond to LH stimulation in vivo, and that alterations in the stru cture and function of the epididymis occur even when the serum concent ration of T is maintained.