Methoxychlor may cause ovarian follicular atresia and proliferation of the ovarian epithelium in the mouse

Methoxychlor (MXC) is currently used to protect agricultural products from insects. Previous studies show that MXC adversely affects the ovary, but the target cells were not revealed by those studies. Therefore, the purpose of this study was to test the hypothesis that MXC induces ovarian changes by adversely affecting the antral follicles and the ovarian surface epithelium in the mouse. To test this hypothesis, cycling female CD-1 mice (39 days) were dosed with MXC (8, 16, or 32 mg/kg/day), kepone (KPN, 8 mg/kg/day, positive control), or sesame oil (vehicle control) via intraperitoneal injection for 10 or 20 days. Estrous cyclicity was evaluated daily via vaginal lavage. After dosing, ovaries were collected for histological evaluation of follicle numbers, atresia, and surface epithelial height. The results indicate that at the 20-day time point, MXC (32 mg/kg) and KPN (8 mg/kg) increased the percentage of atretic antral follicles (n = 4-9, p ≤ 0.001). MXC (32 mg/kg) also increased the height of the ovarian surface epithelium compared with controls (n = 7-10, p ≤ 0.045), and KPN increased the percentage of days in estrus (n = 6-10, p ≤ 0.0001). These data suggest that MXC and KPN increase antral follicle atresia, MXC increases surface epithelial height, and KPN affects vaginal cytology.