Title: Initiation of delayed ovotoxicity by in vitro and in vivo exposures of rat ovaries to 4-vinylcyclohexene diepoxide.

Authors: Devine, Patrick J; Sipes, I Glenn; Hoyer, Patricia B

Published In Reprod Toxicol, (2004 Nov)

Abstract: Repeated daily dosing of rats with the ovotoxic, occupational chemical 4-vinylcyclohexene diepoxide (VCD, 80 mg/kg, i.p.) selectively depletes primordial and primary ovarian follicles. This study was designed to investigate whether follicle loss can be achieved following a single, acute exposure to VCD. Ovaries removed from postnatal-day-4 female Fischer 344 rats were cultured in the absence or presence of VCD for 15 days. Continuous in vitro exposure to VCD (15 days) caused concentration-dependent loss of primordial and small primary follicles. A single exposure to VCD in vitro (30 microM, 24 h) also caused significant losses of primordial and primary follicles 14 days later. Additionally, 28-day-old female rats were given a single injection of VCD (40-320 mg/kg, i.p.). A single dose at 320 mg/kg resulted in substantial loss of all follicle stages beginning 6 days later. Overall, these results demonstrate that an acute exposure to high concentrations/doses of VCD is sufficient to cause subsequent delayed loss of follicles.

PubMed ID: 15336714

MeSH Terms: Animals; Apoptosis*; Cyclohexanes/administration & dosage; Cyclohexanes/toxicity*; Dose-Response Relationship, Drug; Female; In Vitro; Injections, Intraperitoneal; Organ Culture Techniques/methods; Ovarian Follicle/drug effects*; Ovarian Follicle/pathology; Rats; Rats, Inbred F344; Research Support, U.S. Gov't, P.H.S.; Time Factors; Vinyl Compounds/administration & dosage; Vinyl Compounds/toxicity*