Long-term effects of ovarian follicular depletion in rats by 4-vinylcyclohexene diepoxide.

4-Vinylcyclohexene diepoxide (VCD) destroys preantral ovarian follicles in rats. Female 28-day Fisher 344 (F344) rats were dosed (30 days) with VCD (80 mg/kg per day, i.p.) or vehicle, and animals were evaluated for reproductive function at subsequent time points for up to 360 days. At each time point animals were killed, and ovaries and plasma collected. VCD reduced (P<0.05) the number of preantral follicles by day 30 relative to control. There were no ultrastructural differences in morphology between VCD-treated and control ovaries. Circulating FSH levels in VCD-treated animals were greater (days 120, 240, and 360, P<0.05) than in controls. Cyclicity was disrupted in the VCD-treated group by day 360. These results show that VCD-induced follicular destruction in rats is associated with a sequence of events (loss of preantral follicles, increased plasma FSH, and cyclic disruption) preceding premature ovarian senescence that is similar to events that occur during the onset of menopause in women.