A single dose of the ovotoxicant 4-vinylcyclohexene diepoxide is protective in rat primary ovarian follicles

Repeated dosing of rats with the ovotoxic chemical, 4-vinylcyclohexene diep oxide (VCD), destroys primordial and primary ovarian follicles via apoptosi s (physiological cell death) by accelerating the normal rate of atresia. Th e present study investigated the effect of a single dose (1x) of VCD. Immat ure (d28) female Fischer 344 rats were dosed 1x or 15 x with VCD (80 mg/kg ip). Ovaries were collected 24 h or 15 days following 1x VCD or after 15x f or classification and evaluation. Following 1x VCD the number of healthy pr imary follicles was greater (p < 0.05) than control 24 h and 15 days later. This effect reflected a slowing of the normal rate of atresia seen in cont rol ovaries. There was no effect of a single dose on primordial or growing follicles at any time. Expression of mRNA encoding the cell death gene bar was reduced (p < 0.05) on d1 after 1x VCD in isolated primordial and primar y follicles. These observations were in contrast to a decreased (p < 0.05) number of healthy primary and primordial follicles in ovaries and increased (p < 0.05) bar mRNA in isolated follicles from rats dosed 15x for 15 days. Immunofluorescence staining revealed that, the distribution of Bar protein was similar between ovaries from controls and Ix or 15x VCD-treated rats. These data provide evidence for a "protective" response against the normal rate of atresia in primary ovarian follicles following exposure to Ix VCD. Additionally, changes in expression of bar mRNA paralleled alterations in t he rate of atresia. (C) 1999 Academic Press.