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. 2003 Apr;111(4):557–561. doi: 10.1289/ehp.5304

Exposure to 4-tert-octylphenol accelerates sexual differentiation and disrupts expression of steroidogenic factor 1 in developing bullfrogs.

Loretta P Mayer 1, Cheryl A Dyer 1, Catherine R Propper 1
PMCID: PMC1241444  PMID: 12676615

Abstract

Sex-specific gonadal steroidogenesis during development is critical to differentiation of the sexually dimorphic phenotype and reproductive function of adult organisms. Environmental contaminants may affect the process of sexual differentiation through disruption of steroid production and/or action. Control of the steroidogenic metabolic pathway is regulated partly by P450 cytochrome hydroxylases, and the expression of many of these enzymes is controlled by the orphan nuclear receptor, steroidogenic factor-1 (SF-1). In mammals, SF-1 expression is critical for development of the reproductive axis and adult reproductive function. In the bullfrog Rana catesbeiana, during sequential stages of development encompassing sexual differentiation, SF-1 protein expression becomes elevated in ovaries of sexually differentiating females, whereas expression in testes decreases. We exposed tadpoles to the industrial pollutant octylphenol (OP) for 24 hr before and during the critical stages of sexual differentiation to determine whether this known endocrine disruptor affects sex differentiation and SF-1 expression. We found that both females and males treated with an environmentally relevant low dose (10(-9)M) of OP underwent early gonadal differentiation. Furthermore, OP exposure disrupted the sexually dimorphic expression of SF-1 that occurs during sexual differentiation. Our results suggest that OP exposure may affect developmental processes that could ultimately influence adult reproductive function and that these disruptive effects may be mediated in partly through disturbances in gene regulation by SF-1.

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Selected References

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  1. Clements C., Ralph S., Petras M. Genotoxicity of select herbicides in Rana catesbeiana tadpoles using the alkaline single-cell gel DNA electrophoresis (comet) assay. Environ Mol Mutagen. 1997;29(3):277–288. doi: 10.1002/(sici)1098-2280(1997)29:3<277::aid-em8>3.0.co;2-9. [DOI] [PubMed] [Google Scholar]
  2. Colborn T., vom Saal F. S., Soto A. M. Developmental effects of endocrine-disrupting chemicals in wildlife and humans. Environ Health Perspect. 1993 Oct;101(5):378–384. doi: 10.1289/ehp.93101378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Gronen S., Denslow N., Manning S., Barnes S., Barnes D., Brouwer M. Serum vitellogenin levels and reproductive impairment of male Japanese Medaka (Oryzias latipes) exposed to 4-tert-octylphenol. Environ Health Perspect. 1999 May;107(5):385–390. doi: 10.1289/ehp.99107385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Hayes T. B. Sex determination and primary sex differentiation in amphibians: genetic and developmental mechanisms. J Exp Zool. 1998 Aug 1;281(5):373–399. [PubMed] [Google Scholar]
  5. Hayes Tyrone B., Collins Atif, Lee Melissa, Mendoza Magdelena, Noriega Nigel, Stuart A. Ali, Vonk Aaron. Hermaphroditic, demasculinized frogs after exposure to the herbicide atrazine at low ecologically relevant doses. Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5476–5480. doi: 10.1073/pnas.082121499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hsu C. Y., Chang L. T., Ku H. H., Lu M. H. In vitro estradiol synthesis and secretion by tadpole ovaries of different developmental stages. Gen Comp Endocrinol. 1985 Mar;57(3):393–396. doi: 10.1016/0016-6480(85)90220-5. [DOI] [PubMed] [Google Scholar]
  7. Hsü C. Y., Hsü L. H., Liang H. M. The effect of cyproterone acetate on the activity of delta 5-3 beta-hydroxysteroid dehydrogenase in tadpole sex transformation. Gen Comp Endocrinol. 1979 Nov;39(3):404–410. doi: 10.1016/0016-6480(79)90138-2. [DOI] [PubMed] [Google Scholar]
  8. Hsü C. Y., Liang H. M., Hsü L. H. Further evidence for decreased delta5-3beta-hydroxysteroid dehydrogenase activity in female tadpoles after estradiol treatment. Gen Comp Endocrinol. 1978 Aug;35(4):451–454. doi: 10.1016/0016-6480(78)90140-5. [DOI] [PubMed] [Google Scholar]
  9. Ikeda Y., Luo X., Abbud R., Nilson J. H., Parker K. L. The nuclear receptor steroidogenic factor 1 is essential for the formation of the ventromedial hypothalamic nucleus. Mol Endocrinol. 1995 Apr;9(4):478–486. doi: 10.1210/mend.9.4.7659091. [DOI] [PubMed] [Google Scholar]
  10. Ikeda Y., Shen W. H., Ingraham H. A., Parker K. L. Developmental expression of mouse steroidogenic factor-1, an essential regulator of the steroid hydroxylases. Mol Endocrinol. 1994 May;8(5):654–662. doi: 10.1210/mend.8.5.8058073. [DOI] [PubMed] [Google Scholar]
  11. Katsuda S., Yoshida M., Watanabe G., Taya K., Maekawa A. Irreversible effects of neonatal exposure to p-tert-octylphenol on the reproductive tract in female rats. Toxicol Appl Pharmacol. 2000 Jun 15;165(3):217–226. doi: 10.1006/taap.2000.8940. [DOI] [PubMed] [Google Scholar]
  12. Kloas W., Lutz I., Einspanier R. Amphibians as a model to study endocrine disruptors: II. Estrogenic activity of environmental chemicals in vitro and in vivo. Sci Total Environ. 1999 Jan 12;225(1-2):59–68. doi: 10.1016/s0048-9697(99)80017-5. [DOI] [PubMed] [Google Scholar]
  13. Laws S. C., Carey S. A., Ferrell J. M., Bodman G. J., Cooper R. L. Estrogenic activity of octylphenol, nonylphenol, bisphenol A and methoxychlor in rats. Toxicol Sci. 2000 Mar;54(1):154–167. doi: 10.1093/toxsci/54.1.154. [DOI] [PubMed] [Google Scholar]
  14. Lutz I., Kloas W. Amphibians as a model to study endocrine disruptors: I. Environmental pollution and estrogen receptor binding. Sci Total Environ. 1999 Jan 12;225(1-2):49–57. doi: 10.1016/s0048-9697(99)80016-3. [DOI] [PubMed] [Google Scholar]
  15. Majdic G., Sharpe R. M., O'Shaughnessy P. J., Saunders P. T. Expression of cytochrome P450 17alpha-hydroxylase/C17-20 lyase in the fetal rat testis is reduced by maternal exposure to exogenous estrogens. Endocrinology. 1996 Mar;137(3):1063–1070. doi: 10.1210/endo.137.3.8603575. [DOI] [PubMed] [Google Scholar]
  16. Majdic G., Sharpe R. M., Saunders P. T. Maternal oestrogen/xenoestrogen exposure alters expression of steroidogenic factor-1 (SF-1/Ad4BP) in the fetal rat testis. Mol Cell Endocrinol. 1997 Mar 14;127(1):91–98. doi: 10.1016/s0303-7207(96)03998-6. [DOI] [PubMed] [Google Scholar]
  17. Mayer Loretta P., Overstreet Stefanie L., Dyer Cheryl A., Propper Catherine R. Sexually dimorphic expression of steroidogenic factor 1 (SF-1) in developing gonads of the American bullfrog, Rana catesbeiana. Gen Comp Endocrinol. 2002 Jun 1;127(1):40–47. doi: 10.1016/s0016-6480(02)00019-9. [DOI] [PubMed] [Google Scholar]
  18. Noriega N. C., Hayes T. B. DDT congener effects on secondary sex coloration in the reed frog Hyperolius argus: a partial evaluation of the Hyperolius argus endocrine screen. Comp Biochem Physiol B Biochem Mol Biol. 2000 Jun;126(2):231–237. doi: 10.1016/s0305-0491(00)00201-7. [DOI] [PubMed] [Google Scholar]
  19. Pocock Victoria J., Sales Gillian D., Wilson Catherine A., Milligan Stuart R. Effects of perinatal octylphenol on ultrasound vocalization, behavior and reproductive physiology in rats. Physiol Behav. 2002 Aug;76(4-5):645–653. doi: 10.1016/s0031-9384(02)00788-6. [DOI] [PubMed] [Google Scholar]
  20. Saunders P. T., Majdic G., Parte P., Millar M. R., Fisher J. S., Turner K. J., Sharpe R. M. Fetal and perinatal influence of xenoestrogens on testis gene expression. Adv Exp Med Biol. 1997;424:99–110. doi: 10.1007/978-1-4615-5913-9_19. [DOI] [PubMed] [Google Scholar]
  21. Staples C. A., Williams J. B., Blessing R. L., Varineau P. T. Measuring the biodegradability of nonylphenol ether carboxylates, octylphenol ether carboxylates, and nonylphenol. Chemosphere. 1999 Apr;38(9):2029–2039. doi: 10.1016/s0045-6535(98)00415-9. [DOI] [PubMed] [Google Scholar]
  22. White R., Jobling S., Hoare S. A., Sumpter J. P., Parker M. G. Environmentally persistent alkylphenolic compounds are estrogenic. Endocrinology. 1994 Jul;135(1):175–182. doi: 10.1210/endo.135.1.8013351. [DOI] [PubMed] [Google Scholar]

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