The hidden effect of estrogenic/antiandrogenic methoxychlor on spermatogenesis

Perinatal and juvenile oral treatment of rats with methoxychlor (MXC) only during development reduces testicular size and Sertoli cell number in those animals as adults. The objectives were to determine if MXC administered orally reduces numbers of spermatogonia and daily sperm production that parallel reduction in Sertoli cell number and if germ cell degeneration rate or function of individual Sertoli cells was also affected. Rat dams were gavaged with MXC at 0, 5, 50, or 150 mg/kg/day for the week before and after they gave birth. Resulting male pups (14-16 per group) then were dosed directly from postnatal day 7 to 42. Testes were fixed in Bouin's fixative, postfixed in osmium tetroxide, and embedded in Epon. Sections of 0.5 and 20 microm were evaluated stereologically. Across dose groups, body weight was not affected, but testicular weight was significantly reduced in a dose-dependent fashion. Spermatogenic potential based on number of spermatogonia and number of spermatids per testis was significantly reduced by treatment. There was no adverse effect on daily sperm production per gram of parenchyma based on spermatids; however, the number of spermatogonia per gram was reduced. The ratio of spermatid number per spermatogonia was higher in the MXC-treated groups. This difference indicated that the testis can compensate for the treatment-induced reduction in number of spermatogonia by reducing degeneration of their progeny. However, the reduced number of Sertoli cells prevented the compensation from recovering the daily sperm production per testis totally. Given that endocrine disruptors like MXC can induce compensation during spermatogenesis, it may reduce the ability of the testis to compensate during subsequent exposures.