Methoxychlor-Induced Ovarian Follicle Toxicity in Mice: Dose and Exposure Duration-Dependent Effects

Background: Methoxychlor (MXC) is specifically known to target ovarian antral follicles, increasing atresia (death via apoptosis) in them. This is of concern because females are born with a finite pool of ovarian follicles. Only limited studies have explored the phenomenon of a reduced fertility threshold for effect based on the percentage of antral follicle atresia. Methods: In this article, we report on adult female CD-1 mice exposed intraperitoneally to various doses of MXC for 5, 10, 20, and 30 days. In the 20-day treatment, mice were dosed with either the vehicle or MXC at 64 or 96 mg/kg/day, whereas in the 30-day treatment, mice were dosed with vehicle or MXC at 48, 64, or 96 mg/kg/day. The mice that were dosed with MXC for 30 days were also mated with untreated males for a determination of overall fertility. Results: A significantly increased percentage (50%) of atretic antral follicles was observed only after 20 and 30 days of treatment. Specifically, mice treated with MXC64 for 20 and 30 days had an increased percentage of atretic antral follicles compared with vehicle-treated mice. Interestingly, mice dosed with MXC96 had an increased percentage of atretic antral follicles after 30 days, but not after 20 days of treatment compared with vehicle-treated mice. Overall fertility of the mice was not different compared with controls. Conclusions: The results indicate that as much as a 50% increase in atretic antral follicles does not affect the immediate fertility of the mice.