Reduced Ability of Rat Preantral Ovarian Follicles to Metabolize 4-Vinyl-1-cyclohexene Diepoxide in Vitro

J. A. Flaws, K. L. Salyers, I. G. Sipes, P. B. Hoyer

Research output: Contribution to journalArticle

Abstract

4-Vinylcyclohexene diepoxide (1-epoxyethyl-3,4-epoxycyclohexane, VCD), an industrial chemical, is a potential health hazard because it destroys oocytes in small preantral follicles in rats. We proposed that VCD destroys oocytes in these follicles because of their reduced capacity to detoxify VCD (convert VCD to tetrol, 4-(1,2-dihydroxy)ethyl-1,2-dihydroxycyclohexane). Ovaries, livers, and adrenal glands were collected from immature and mature Fischer 344 rats. Tissues were dissociated and ovarian tissue was separated into distinct follicular fractions. Tissues were incubated with [14C]VCD and media were assayed for [14C]tetrol by HPLC. In immature rats, conversion of VCD to tetrol in large preantral follicles and hepatocytes was 1.5-fold greater than in small preantral follicles and 4-fold greater than in ovarian interstitial cells (p <0.05). In adults, conversion of VCD to tetrol in targe preantral follicles and hepatocytes was, respectively, 3- and 10-fold greater than in small preantral follicles and interstitial cells (p <0.05). Compared with immature rats, all tissues from adult rats converted more VCD to tetrol (p <0.05). These data demonstrate that interstitial cells and small preantral follicles from adult and immature rats have a reduced capacity to convert VCD to tetrol compared to large preantral follicles and liver cells. This may explain their increased susceptibility to VCD-induced ovotoxicity. Furthermore, adult rats may be less susceptible to VCD-induced ovotoxicity than immature rats.

Original languageEnglish (US)
Pages (from-to)286-294
Number of pages9
JournalToxicology and Applied Pharmacology
Volume126
Issue number2
DOIs
StatePublished - Jun 1994
Externally publishedYes

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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