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Toxicol Appl Pharmacol. 1999 Aug 1;158(3):244-52.

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

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Department of Physiology, University of Arizona, Tucson, Arizona, 85724, USA.


Repeated dosing of rats with the ovotoxic chemical, 4-vinylcyclohexene diepoxide (VCD), destroys primordial and primary ovarian follicles via apoptosis (physiological cell death) by accelerating the normal rate of atresia. The present study investigated the effect of a single dose (1x) of VCD. Immature (d28) female Fischer 344 rats were dosed 1x or 15x with VCD (80 mg/kg ip). Ovaries were collected 24 h or 15 days following 1x VCD or after 15x for classification and evaluation. Following 1x VCD the number of healthy primary 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 control 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 bax was reduced (p < 0.05) on d1 after 1x VCD in isolated primordial and primary 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) bax mRNA in isolated follicles from rats dosed 15x for 15 days. Immunofluorescence staining revealed that, the distribution of Bax protein was similar between ovaries from controls and 1x 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 1x VCD. Additionally, changes in expression of bax mRNA paralleled alterations in the rate of atresia.

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