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Mechanisms of Ovotoxicity Induced by Environmental Chemicals: 4-Vinylcyclohexene Diepoxide as a Model Chemical

  • Patricia B. Hoyer
  • Ellen A. Cannady
  • Nicole A. Kroeger
  • I. Glenn Sipes
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 500)

Abstract

Females are born with a finite number of undeveloped, primordial follicles. Environmental chemicals that destroy oocytes contained in these follicles can produce premature ovarian failure (early menopause in women) because once destroyed, they cannot be replaced. Menopause is known to be associated with an increased incidence of a variety of health problems such as osteoporosis, cardiovascular disease, and ovarian cancer. Exposure of women to chemicals that are ovotoxic in laboratory animals (chemotherapeutic agents, contaminants of cigarette smoke) is known to be associated with early menopause. Therefore, an overall understanding of mechanisms involved in chemical-induced ovotoxicity is of general health-related concern (Hoyer and Sipes, 1996).

Keywords

Ovarian Follicle Primordial Follicle Premature Ovarian Failure Preantral Follicle Mouse Ovary 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. E.S. Alnemri, D.J. Livingston, D.W. Nicholson, G. Salvesen, N.A. Thornberry, W.W. Wong, and J. Yuan, Human ICE/CED-3 protease nomenclature.Cell87:171 (1996).PubMedCrossRefGoogle Scholar
  2. M. Bengtsson, J. Montelius, L. Mankowitz, and J. Rydstrom, Metabolism of polycyclic aromatic hydrocarbons in the rat ovary.Bloch. Pharmacol.32:129 (1983).CrossRefGoogle Scholar
  3. S.M. Borman, B.J. VanDePol, S.W. Kao, K.E. Thompson, I.G. Sipes, and P.B.Hoyer, A single dose of the ovotoxicant 4-vinylcyclohexene diepoxide is protective in rat primary ovarian follicles.Toxicol. Appl. Pharmacol.158:244 (1999).PubMedCrossRefGoogle Scholar
  4. G.A. Csanady, F.P. Guengerich, J.A. Bond, Comparison of the biotransformation of 1,3-butadiene and its metabolite, butadiene monoepoxide by hepatic and pulmonary tissues from humans, rats and mice.Carcinogenesis13:1143 (1992).PubMedCrossRefGoogle Scholar
  5. J.K. Doerr, S.B. Hooser, B.J. Smith, and I.G. Sipes, Ovarian toxicity of 4-vinylcyclohexene and related olefins in B6C3F1 mice: Role of diepoxides.Chem. Res. Toxicol.8:963 (1995).PubMedCrossRefGoogle Scholar
  6. J.K. Doerr-Stevens, J. Liu, G.J. Stevens, J.C. Kraner, S.M. Fontaine, J.R. Halpert, and I.G. Sipes, Induction of cytochrome P-450 enzymes after repeated exposure to 4-vinylcyclohexene in B6C3F1 mice.Drug Metab. Disp27(2):281–287 (1999).Google Scholar
  7. J.A. Flaws, K.L. Salyers, I.G. Sipes, and P.B. Hoyer, Reduced ability of rat pre-antral ovarian follicles to metabolize 4-vinyl-1-cyclohexene diepoxide in vitro.Tox. Appl. Phannacol. 126:286 (1994).CrossRefGoogle Scholar
  8. W.L. Heinrichs, and M.R. Juchau, Extrahepatic drug metabolism: The gonads. In: Extrahepatic Metabolism of Drugs and Other Foreign Compounds, TE Gram (ed), SP Medical and Scientific Books, New York, pp. 319 (1980).Google Scholar
  9. A.N. Hirshfield, Development of follicles in the mammalian ovary. Int. Rev. Cytol. 124 (1991).Google Scholar
  10. A.N. Hirshfield, and W.A. Schmidt, Kinetic aspects of follicular development in the rat. In: Regulation of Ovarian and Testicular Function. ed. VB Mahesh, DS Dindsa, NY Plenum Press New York pp. 211–237 (1987).CrossRefGoogle Scholar
  11. S.B. Hooser, D.P. Douds, D.G. DeMerell, P.B. Hoyer, and I.G. Sipes, Long-term ovarian and gonadotropin changes in mice exposed to 4-vinylcyclohexene Reprod. Toxicol.8:315 (1994).PubMedCrossRefGoogle Scholar
  12. P.B. Hoyer, and I.G. Sipes, Assessment of follicle destruction in chemical-induced ovarian toxicity. Ann. Rev. Pharmacol. Toxicol.36:307–331 (1996).CrossRefGoogle Scholar
  13. S.W. Kao, I.G. Sipes, and P.B. Hoyer, Early effects of ovotoxicity induced by 4-vinylcyclohexene diepoxide in rats and mice.Reprod. Toxicol.13:67 (1999).PubMedCrossRefGoogle Scholar
  14. H. Mukhtar, R.M. Philpot, and J.B. Bend, The postnatal development of microsomal epoxide hydrase, cytosolic glutathione S-transferase, and mitochondrial and microsomal cytochrome P-450 in adrenals and ovaries of female rats.Drug Metab. Disp.6:577 (1978a).Google Scholar
  15. H. Mukhtar, R.M. Philpot, and J.R. Bend, Metabolizing enzyme activities and cytochrome P-450 content of rat ovaries during pregnancy.Bioch. Bioph. Res. Comm.81:89 (1978b).CrossRefGoogle Scholar
  16. National Toxicology Program, Toxicology and carcinogenesis studies of 4-vinylcyclohexene in F344/N rats and B6C3F1 mice. NTP Tec. Rep. No. 303US Dept. Health Hum. Serv. Public Health Serv. Natl. Inst. Health. Public Inf. Natl. Toxicol. Program, Research Triangle Park NC. (1986).Google Scholar
  17. K.L. Salyers, W. Zheng, and I.G. Sipes, Disposition and toxicokinetics of 4-vinyl-1-cyclohexene diepoxide in female F344 rats and B6C3F1 mice, ISSX Proc4:Abstract 169 (1993).Google Scholar
  18. Simmon VF nd Baden JM (1980). Mutagenic activity of vinyl compounds and derived epoxides.Mutat. Res.78:227–231.CrossRefGoogle Scholar
  19. B.J. Smith, D.R. Mattison, and I.G. Sipes, The role of epoxidation in 4-vinylcyclohexene-induced ovarian toxicity.Toxicol. Appl. Pharmacol.105:372 (1990a).PubMedCrossRefGoogle Scholar
  20. B.J. Smith, I.G. Sipes, J.C. Stevens, and J.R. Halpert, The biochemical basis for the species difference in hepatic microsomal 4-vinylcyclohexene epoxidation between female mice and rats.Carcinogenesis11:1951 (1990b).PubMedCrossRefGoogle Scholar
  21. L.N. Springer, M.E. McAsey, J.A. Flaws, J.L. Tilly, I.G. Sipes, and P.B. Hoyer, Involvement of apoptosis in 4-vinylcyclohexene diepoxide-induced ovotoxicity in rats.Toxicol Appl. Pharmacol.139:394 (1996a).PubMedCrossRefGoogle Scholar
  22. L.N. Springer, J.L. Tilly, I.G. Sipes, and P.B. Hoyer, Enhanced expression ofbaxin small preantral follicles during 4-vinylcyclohexene diepoxide-induced ovotoxicity in the rat.Toxicol Appl. Pharmacol.139:402 (1996b).PubMedCrossRefGoogle Scholar
  23. C.E Voogd, J.J. VanderStel, and J.A. Jacobs, The mutagenic action of aliphatic epoxides. Mutat. Res.89:269 (1981).PubMedCrossRefGoogle Scholar
  24. K.G. Wolter, Y.T. Hsu, C.L. Smith, A. Nechushtan, X.G. Xi, and Y.J. Youle, Movement of Bax from the Cytosol to Mitochondria during Apoptosis.J. Cell Biol.139: 1281 (1997).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Patricia B. Hoyer
    • 1
  • Ellen A. Cannady
    • 2
  • Nicole A. Kroeger
    • 1
  • I. Glenn Sipes
    • 2
  1. 1.Department of PhysiologySouthwest Environmental Health Sciences Center The University of ArizonaUSA
  2. 2.Department of Pharmacology and ToxicologySouthwest Environmental Health Sciences Center The University of ArizonaUSA

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