Involvement of apoptosis in 4-vinylcyclohexene diepoxide-induced ovotoxicity in rats

L. N. Springer, M. E. McAsey, J. A. Flaws, J. L. Tilly, I. G. Sipes, P. B. Hoyer

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114 Scopus citations


Previous studies have determined that 4-vinylcyclohexene diepoxide (VCD) causes specific destruction of oocytes contained in small pre-antral (primordial and primary) ovarian follicles of Fischer 344 rats following 30 days of daily dosing with VCD. The purposes of this study were to identify the type of VCD-induced cell death occurring in small pre-antral follicles and to determine the earliest time following the onset of dosing when evidence of follicular destruction could first be detected. A significant decrease in the number of oocytes contained in small pre-antral follicles in ovaries of rats after 15 days of daily dosing (ip) with VCD (80 mg/kg) had been observed in preliminary experiments. Therefore, a study was conducted to determine the time of the onset of this follicular destruction by examination of follicular DNA integrity. Female Fischer 344 rats were dosed daily (80 mg/kg, ip) for 6, 8, 10, 12, or 14 days, and ovaries were removed 1, 4, or 24 hr after the final dose. Small pre-antral follicles (25-100 μm) were isolated by gentle dissociation of ovaries with collagenase, and follicles were sorted with micropipets. Genomic DNA was isolated from follicles and radiolabeled with [32P]dideoxy ATP, and the degree of fragmentation quantified by agarose gel electrophoresis and autoradiography. Degradation of DNA was evaluated by 32P content in low-molecular-weight fragments (

Original languageEnglish (US)
Pages (from-to)394-401
Number of pages8
JournalToxicology and Applied Pharmacology
Issue number2
StatePublished - Aug 1996
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology


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