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Pathogenic Reactions of the Ovarian Surface Epithelium to Ovulation, Dimethylbenzanthracene, and Estrogen are Negated by Vitamin E

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Abstract

Objective: Acute effects of ovulation, the tumor suppressor disruptor dimethylbenzanthracene, the mitogen estradiol-17β, and the antioxidant vitamin E on the ovarian epithelium were assessed in seasonally anestrous ewes. Methods: Dimethylbenzanthracene and vitamin E were administered before and estradiol after gonadotropin-induced ovulation. Ovaries were removed for histopathology one and three weeks following ovulation. Surface epithelial cells isolated at one week were immunostained for 8-oxoguanine and assayed for urokinase plasminogen activator secretion—markers of genotoxic and invasive potentials. Results: Ovarian surface invaginations and cortical inclusion cysts containing stratified epithelium were observed at three weeks in ovulated animals treated with dimethylbenzanthracene and estradiol. Progenitor cells were 8-oxoguanine positive and hypersecreted urokinase plasminogen activator. Untoward responses were circumvented by vitamin E. Conclusion: Antioxidant therapy appears to be of value in precluding periovulatory disturbances to the ovarian surface epithelium that has been associated with carcinogenesis.

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References

  1. Auersperg A., Wong AST, Choi K.-Y., Kang SK, Leung PCK. Ovarian surface epithelium: biology, endocrinology, and pathology. Endocr Rev. 2001;22:255–288.

    CAS  PubMed  Google Scholar 

  2. Bandera CA Advances in the understanding of risk factors for ovarian cancer. J Reprod Med. 2005;50:399–406.

    PubMed  Google Scholar 

  3. Mahdavi A., Pejovic T., Nezhat F. Induction of ovulation and ovarian cancer: a critical review of the literature. Fertil Steril. 2006;85:819–826.

    Article  CAS  PubMed  Google Scholar 

  4. Murdoch WJ Proteolytic and cellular death mechanisms in ovulatory ovarian rupture. Biol Signals Receptors. 2000;9: 102–114.

    Article  CAS  Google Scholar 

  5. Murdoch WJ Carcinogenic potential of ovulatory genotoxicity. Biol Reprod. 2005;73:586–590.

    Article  CAS  PubMed  Google Scholar 

  6. Aunoble B., Sanches R., Didier E., Bignon YJ Major oncogenes and tumor suppressor genes involved in epithelial ovarian cancer. Int J Oncol. 2000;16:567–576.

    CAS  PubMed  Google Scholar 

  7. Murdoch WJ, Van Kirk EA Steroid hormonal regulation of proliferative, p53 tumor suppressor, and apoptotic responses of sheep ovarian surface epithelial cells. Molec Cell Endocrinol. 2002;186:61–67.

    Article  CAS  PubMed  Google Scholar 

  8. Leung PC, Choi JH Endocrine signaling in ovarian surface epithelium and cancer. Hum Reprod Update. 2007;13:143–162.

    Article  CAS  PubMed  Google Scholar 

  9. Bast RC Jr, Brewer M., Zou C., et al. Prevention and early detection of ovarian cancer: mission impossible? Recent Results Cancer Res. 2007;174:91–100.

    Article  CAS  PubMed  Google Scholar 

  10. Fairfield KM, Hankinson SE, Rosner BA, Hunter DJ, Colditz GA, Willett WC Risk of ovarian carcinoma and consumption of vitamins A, C, and E and specific carotenoids. Cancer. 2001;92:2318–2326.

    Article  CAS  PubMed  Google Scholar 

  11. McCann SE, Moysich KB, Mettlin C. Intakes of selected nutrients and food groups and risk of ovarian cancer. Nutr Cancer. 2001;39:19–28.

    Article  CAS  PubMed  Google Scholar 

  12. Senthil K., Aranganathan S., Nalini N. Evidence of oxidative stress in the circulation of ovarian cancer patients. Clin Chim Acta. 2004;339:27–32.

    Article  CAS  PubMed  Google Scholar 

  13. Murdoch WJ, Martinchick JF Oxidative damage to DNA of ovarian surface epithelial cells affected by ovulation: carcinogenic implication and chemoprevention. Exp Biol Med. 2004;229:553–559.

    Article  Google Scholar 

  14. Stewart SL, Querec TD, Ochman AR, et al. Characterization of a carcinogenesis rat model of ovarian preneoplasia and neoplasia. Cancer Res. 2004;64:8177–8183.

    Article  CAS  PubMed  Google Scholar 

  15. Roberts AJ, Dunn TG, Murdoch WJ Induction of ovulation in proestrous ewes: identification of the ovulatory follicle and functional status of the corpus luteum. Domest Anim Endocrinol. 1985;2:207–210.

    Article  CAS  Google Scholar 

  16. Eggleston DL, Wilken C., Van Kirk EA, Slaughter RG, Ji TH, Murdoch WJ Progesterone induces expression of endometrial messenger RNA encoding for cyclooxygenase. Prostaglandins. 1990;39:675–683.

    Article  CAS  PubMed  Google Scholar 

  17. Field RA, Maiorano G., Hinds FC, Murdoch WJ, Riley ML Bone ossification and carcass characteristics of wethers given silastic implants containing estradiol. J Anim Sci. 1990;68:3663–8.

    Article  CAS  PubMed  Google Scholar 

  18. Murdoch J., Van Kirk EA, Murdoch WJ Hormonal control of urokinase plasminogen activator secretion by sheep ovarian surface epithelial cells. Biol Reprod. 1999;61:1487–1491.

    Article  CAS  PubMed  Google Scholar 

  19. Murdoch WJ, Townsend RS, McDonnel AC Ovulation-induced DNA damage in ovarian surface epithelial cells of ewes: prospective regulatory mechanisms of repair/survival and apoptosis. Biol Reprod. 2001;65:1417–24.

    Article  CAS  PubMed  Google Scholar 

  20. Nishida T., Sugiyama T., Kataoka A., Ushijima K., Yakushiji M. Histologic characterization of rat ovarian carcinoma induced by intraovarian insertion of a 7, 12-dimethylbenz[a]anthracene-coated suture: common epithelial tumors of the ovary in rats? Cancer. 1998;83:965–970.

    Article  CAS  PubMed  Google Scholar 

  21. Clow OL, Hurst PR, Fleming JS Changes in the mouse ovarian surface epithelium with age and ovulation number. Molec Cell Endocrinol. 2002;191:105–11.

    Article  CAS  PubMed  Google Scholar 

  22. Flesken-Nikitin A., Choi K.-C., Eng JP, Shmidt EN, Nikitin AY Induction of carcinogenesis by concurrent inactivation of p53 and Rb1 in the mouse ovarian surface epithelium. Cancer Res. 2003;63:3459–3463.

    CAS  PubMed  Google Scholar 

  23. Celik C., Gezginc K., Aktan M., et al. Effects of ovulation induction on ovarian morphology: an animal study. Int J Gynecol Cancer. 2004;14:600–606.

    Article  CAS  PubMed  Google Scholar 

  24. Crist KA, Zhang Z., You M., et al. Characterization of rat ovarian adenocarcinomas developed in response to direct instillation of 7,12-dimethylbenz[a]anthracene (DMBA) coated suture. Carcinogenesis. 2005;26:951–957.

    Article  CAS  PubMed  Google Scholar 

  25. Tan OL, Hurst PR, Fleming JS Location of inclusion cysts in mouse ovaries in relation to age, pregnancy, and total ovulation number: implications for ovarian cancer? J Pathol. 2005;205:483–490.

    Article  PubMed  Google Scholar 

  26. Burdette JE, Kurley SJ, Kilen SM, Mayo KE, Woodruff TK Gonadotropin-induced superovulation drives ovarian surface epithelia proliferation in CD1 mice. Endocrinology. 2006;147:2338–2345.

    Article  CAS  PubMed  Google Scholar 

  27. Burdette JE, Oliver RM, Ulyanov V., Kilen SM, Mayo KE, Woodruff TK Ovarian epithelial inclusion cysts in chronically superovulated CD1 and Smad2 dominant-negative mice. Endocrinology. 2007;148:3595–3604.

    Article  CAS  PubMed  Google Scholar 

  28. Gotfredson GS, Murdoch WJ Morphologic responses of the mouse ovarian surface epithelium to ovulation and steroid hormonal milieu. Exp Biol Med. 2007;232:277–280.

    CAS  Google Scholar 

  29. Ting AY, Kimler BF, Fabian CJ, Petroff BK Characterization of a preclinical model of simultaneous breast and ovarian cancer progression. Carcinogenesis. 2007;28:130–135.

    Article  CAS  PubMed  Google Scholar 

  30. Auersperg N., Edelson MI, Mok SC, Johnson SW, Hamilton TC The biology of ovarian cancer. Semin Oncol. 1998;25:281–304.

    CAS  PubMed  Google Scholar 

  31. Fredrickson TN Ovarian tumors of the hen. Environ Health Perspect. 1978;73:35–51.

    Article  Google Scholar 

  32. Damjanov I. Ovarian tumours in laboratory and domestic animals. Curr Top Pathol. 1989;78:1–10.

    Article  CAS  PubMed  Google Scholar 

  33. Rodriguez-Burford C., Barnes MN, Berry W., Partridge EE, Grizzle WE Immunohistochemical expression of molecular markers in an avian model: a potential model for preclinical evaluation of agents for ovarian cancer chemoprevention. Gynecol Oncol. 2001;81:373–379.

    Article  CAS  PubMed  Google Scholar 

  34. Owen JA JrPhysiology of the menstrual cycle. Am J Clin Nutr. 1975;28:333–338.

    Article  CAS  PubMed  Google Scholar 

  35. Cunat S., Hoffman P., Pujol P. Estrogens and epithelial ovarian cancer. Gynecol Oncol. 2004;94:25–32.

    Article  CAS  PubMed  Google Scholar 

  36. Grollman AP, Moriya M. Mutagenesis by 8-oxoguanine: an enemy within. Trends Genet. 1993;9:246–249.

    Article  CAS  PubMed  Google Scholar 

  37. McDonnel Smedts A., Curry TE, Murdoch WJ Proteolytic enzymes and their inhibition in epithelial ovarian cancer. Curr Enz Inhib. 2005;1:157–170.

    Article  Google Scholar 

  38. Azzi A., Ricciarelli R., Zingg JM Non-antioxidant molecular functions of alpha-tocopherol (vitamin E). FEBS Lett. 2002;519:8–10.

    Article  CAS  PubMed  Google Scholar 

  39. Claycombe KJ, Meydani SN Vitamin E and genome stability. Mutat Res. 2001;475:37–44.

    Article  CAS  PubMed  Google Scholar 

  40. Kline K., Yu W., Sanders BG, Vitamin E.: mechanisms of action as tumor cell growth inhibitors. J Nutr. 2001;131:161S–163S.

    Article  CAS  PubMed  Google Scholar 

  41. Ricciarelli R., Zingg JM, Azzi A. Vitamin E: protective role of a Janus molecule. FASEB J. 2001;15:2314–2325.

    Article  CAS  PubMed  Google Scholar 

  42. Ogston D. Inhibition of the plasminogen activator urokinase by alpha-tocopherol. Acta Haematol. 1982;67:114–118.

    Article  CAS  PubMed  Google Scholar 

  43. Navarro Silvera SA, Jain M., Howe GR, Miller AB, Rohan TE Carotenoid, vitamin A, vitamin C, vitamin E, intake and risk of ovarian cancer: a prospective cohort study. Cancer Epidemiol Biomarkers Prev. 2006;15:395–397.

    Article  CAS  Google Scholar 

  44. Herrera E., Barbas C. Vitamin E: action, metabolism and perspectives. J Physiol Biochem. 2001;57:43–56.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to William J. Murdoch PhD.

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Murdoch, W.J., Van Kirk, E.A. & Shen, Y. Pathogenic Reactions of the Ovarian Surface Epithelium to Ovulation, Dimethylbenzanthracene, and Estrogen are Negated by Vitamin E. Reprod. Sci. 15, 839–845 (2008). https://doi.org/10.1177/1933719108322435

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