Skip to main content
NCBI home page
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 2001 Oct;109(10):1063–1070. doi: 10.1289/ehp.011091063

Antiandrogenic pesticides disrupt sexual characteristics in the adult male guppy Poecilia reticulata.

E Baatrup 1, M Junge 1
PMCID: PMC1242084  PMID: 11675272

Abstract

Environmental contaminants have been identified as endocrine disruptors through their antiandrogenic activity. Thus, as androgen receptor antagonists, the fungicide vinclozolin and the principal DDT metabolite p,p'-DDE have been demonstrated to induce demasculinization in rats. Whether this is also the case in fish remains to be demonstrated. For a period of 30 days, groups of adult male guppies were exposed to vinclozolin, p,p'-DDE, or the therapeutic antiandrogen flutamide (used as positive control) applied to the fodder at concentrations between 0.1 and 100 microg/g fodder. Subsequently, sexual characteristics of relevance to the male reproductive capacity were measured and compared with untreated control fish. All three chemicals caused profound alterations at increasing levels of biological organization, even in these fully matured males. At the cellular level, the three compounds induced a significant reduction in the number of ejaculated sperm cells. At the organ level, the sexually attractive orange-yellow coloration was reduced in area and discolored, and treated fish also had smaller testes. Further, at the organismal level, computer-aided behavior analyses demonstrated a severe disruption in male courtship behavior. We conclude that this demasculinization is consistent with an antiandrogenic action of vinclozolin and p,p'-DDE and is likely to compromise reproductive capability in this fish.

Full Text

The Full Text of this article is available as a PDF (591.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arnold S. F., Vonier P. M., Collins B. M., Klotz D. M., Guillette L. J., Jr, McLachlan J. A. In vitro synergistic interaction of alligator and human estrogen receptors with combinations of environmental chemicals. Environ Health Perspect. 1997 Apr;105 (Suppl 3):615–618. doi: 10.1289/ehp.97105s3615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ashby J., Lefevre P. A. The weanling male rat as an assay for endocrine disruption: preliminary observations. Regul Toxicol Pharmacol. 1997 Dec;26(3):330–337. doi: 10.1006/rtph.1997.1177. [DOI] [PubMed] [Google Scholar]
  3. Balbontin J. B., Ferrario M. Effects of cyproterone acetate on the reproductive tract and pituitary-gonadal axis of the golden hamster. Andrologia. 1993 Sep-Oct;25(5):289–292. doi: 10.1111/j.1439-0272.1993.tb02727.x. [DOI] [PubMed] [Google Scholar]
  4. Bayley M., Nielsen J. R., Baatrup E. Guppy sexual behavior as an effect biomarker of estrogen mimics. Ecotoxicol Environ Saf. 1999 May;43(1):68–73. doi: 10.1006/eesa.1999.1766. [DOI] [PubMed] [Google Scholar]
  5. Burns L. A., Butterworth L. F., Munson A. E. Reversal of gallium arsenide-induced suppression of the antibody response by a mixed disulfide metabolite of meso-2,3-dimercaptosuccinic acid. J Pharmacol Exp Ther. 1993 Feb;264(2):695–700. [PubMed] [Google Scholar]
  6. Carlson D. B., Curtis L. R., Williams D. E. Salmonid sexual development is not consistently altered by embryonic exposure to endocrine-active chemicals. Environ Health Perspect. 2000 Mar;108(3):249–255. doi: 10.1289/ehp.00108249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chapin R. E., Stevens J. T., Hughes C. L., Kelce W. R., Hess R. A., Daston G. P. Endocrine modulation of reproduction. Fundam Appl Toxicol. 1996 Jan;29(1):1–17. doi: 10.1006/faat.1996.0001. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Consensus development meeting 1995: combined oral contraceptives and cardiovascular disease. The Consensus Statement issued after the Second European Conference on Sex Steroids and Metabolism, Amsterdam, November 1995. Writing Committee. Gynecol Endocrinol. 1996 Feb;10(1):1–5. [PubMed] [Google Scholar]
  10. Gray L. E., Jr, Ostby J. S., Kelce W. R. Developmental effects of an environmental antiandrogen: the fungicide vinclozolin alters sex differentiation of the male rat. Toxicol Appl Pharmacol. 1994 Nov;129(1):46–52. doi: 10.1006/taap.1994.1227. [DOI] [PubMed] [Google Scholar]
  11. Gray L. E., Jr, Ostby J. Effects of pesticides and toxic substances on behavioral and morphological reproductive development: endocrine versus nonendocrine mechanisms. Toxicol Ind Health. 1998 Jan-Apr;14(1-2):159–184. doi: 10.1177/074823379801400111. [DOI] [PubMed] [Google Scholar]
  12. Gray L. E., Jr, Ostby J., Monosson E., Kelce W. R. Environmental antiandrogens: low doses of the fungicide vinclozolin alter sexual differentiation of the male rat. Toxicol Ind Health. 1999 Jan-Mar;15(1-2):48–64. doi: 10.1177/074823379901500106. [DOI] [PubMed] [Google Scholar]
  13. Guillette L. J., Jr, Gross T. S., Masson G. R., Matter J. M., Percival H. F., Woodward A. R. Developmental abnormalities of the gonad and abnormal sex hormone concentrations in juvenile alligators from contaminated and control lakes in Florida. Environ Health Perspect. 1994 Aug;102(8):680–688. doi: 10.1289/ehp.94102680. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Guillette L. J., Jr, Pickford D. B., Crain D. A., Rooney A. A., Percival H. F. Reduction in penis size and plasma testosterone concentrations in juvenile alligators living in a contaminated environment. Gen Comp Endocrinol. 1996 Jan;101(1):32–42. doi: 10.1006/gcen.1996.0005. [DOI] [PubMed] [Google Scholar]
  15. Haider S. G. Histophysiological effects of an antiandrogen (cyproterone acetate) on the testis of the frog Rana temporaria. Acta Anat (Basel) 1980;106(3):387–391. doi: 10.1159/000145204. [DOI] [PubMed] [Google Scholar]
  16. Kelce W. R., Lambright C. R., Gray L. E., Jr, Roberts K. P. Vinclozolin and p,p'-DDE alter androgen-dependent gene expression: in vivo confirmation of an androgen receptor-mediated mechanism. Toxicol Appl Pharmacol. 1997 Jan;142(1):192–200. doi: 10.1006/taap.1996.7966. [DOI] [PubMed] [Google Scholar]
  17. Kelce W. R., Monosson E., Gamcsik M. P., Laws S. C., Gray L. E., Jr Environmental hormone disruptors: evidence that vinclozolin developmental toxicity is mediated by antiandrogenic metabolites. Toxicol Appl Pharmacol. 1994 Jun;126(2):276–285. doi: 10.1006/taap.1994.1117. [DOI] [PubMed] [Google Scholar]
  18. Kelce W. R., Stone C. R., Laws S. C., Gray L. E., Kemppainen J. A., Wilson E. M. Persistent DDT metabolite p,p'-DDE is a potent androgen receptor antagonist. Nature. 1995 Jun 15;375(6532):581–585. doi: 10.1038/375581a0. [DOI] [PubMed] [Google Scholar]
  19. Kelce W. R., Wilson E. M. Environmental antiandrogens: developmental effects, molecular mechanisms, and clinical implications. J Mol Med (Berl) 1997 Mar;75(3):198–207. doi: 10.1007/s001090050104. [DOI] [PubMed] [Google Scholar]
  20. Kime D. E. A strategy for assessing the effects of xenobiotics on fish reproduction. Sci Total Environ. 1999 Jan 12;225(1-2):3–11. doi: 10.1016/s0048-9697(98)00328-3. [DOI] [PubMed] [Google Scholar]
  21. Liley N. R. The endocrine control of reproductive behaviour in the female guppy, Poecilia reticulata peters. Anim Behav. 1968 Apr-Jul;16(2):318–331. doi: 10.1016/0003-3472(68)90016-x. [DOI] [PubMed] [Google Scholar]
  22. Loeffler I. K., Peterson R. E. Interactive effects of TCDD and p,p'-DDE on male reproductive tract development in in utero and lactationally exposed rats. Toxicol Appl Pharmacol. 1999 Jan 1;154(1):28–39. doi: 10.1006/taap.1998.8572. [DOI] [PubMed] [Google Scholar]
  23. Makynen EA, Kahl MD, Jensen KM, Tietge JE, Wells KL, Van Der Kraak G, Ankley GT. Effects of the mammalian antiandrogen vinclozolin on development and reproduction of the fathead minnow (Pimephales promelas). Aquat Toxicol. 2000 Apr 1;48(4):461–475. doi: 10.1016/s0166-445x(99)00059-4. [DOI] [PubMed] [Google Scholar]
  24. Meriggiola M. C., Bremner W. J., Costantino A., Pavani A., Capelli M., Flamigni C. An oral regimen of cyproterone acetate and testosterone undecanoate for spermatogenic suppression in men. Fertil Steril. 1997 Nov;68(5):844–850. doi: 10.1016/s0015-0282(97)00363-4. [DOI] [PubMed] [Google Scholar]
  25. Monosson E., Kelce W. R., Lambright C., Ostby J., Gray L. E., Jr Peripubertal exposure to the antiandrogenic fungicide, vinclozolin, delays puberty, inhibits the development of androgen-dependent tissues, and alters androgen receptor function in the male rat. Toxicol Ind Health. 1999 Jan-Mar;15(1-2):65–79. doi: 10.1177/074823379901500107. [DOI] [PubMed] [Google Scholar]
  26. Moorman W. J., Cheever K. L., Skaggs S. R., Clark J. C., Turner T. W., Marlow K. L., Schrader S. M. Male adolescent exposure to endocrine-disrupting pesticides: vinclozolin exposure in peripubertal rabbits. Andrologia. 2000 Sep;32(4-5):285–293. doi: 10.1046/j.1439-0272.2000.00400.x. [DOI] [PubMed] [Google Scholar]
  27. Pandey S. Effects of hypophysectomy on the testis and secondary sex characters of the adult guppy Poecilia reticulata Peters. Can J Zool. 1969 Sep;47(5):775–781. doi: 10.1139/z69-134. [DOI] [PubMed] [Google Scholar]
  28. Pandey S. Effects of methyl testosterone on the testis and secondary sex characters of the hypophysectomized adult guppy Poecilia reticulata Peters. Can J Zool. 1969 Sep;47(5):783–786. doi: 10.1139/z69-135. [DOI] [PubMed] [Google Scholar]
  29. Pandey S. The role of pituitary and gonadal hormones in the differentiation of testis and secondary sex characters of the juvenile guppy Poecilia reticulata peters. Biol Reprod. 1969 Sep;1(3):272–281. doi: 10.1095/biolreprod1.3.272. [DOI] [PubMed] [Google Scholar]
  30. Roberts K. P., Zirkin B. R. Androgen regulation of spermatogenesis in the rat. Ann N Y Acad Sci. 1991;637:90–106. doi: 10.1111/j.1749-6632.1991.tb27303.x. [DOI] [PubMed] [Google Scholar]
  31. Rouse E. F., Coppenger C. J., Barnes P. R. The effect of an androgen inhibitor on behavior and testicular morphology in the stickleback Gasterosteus aculeatus. Horm Behav. 1977 Aug;9(1):8–18. doi: 10.1016/0018-506x(77)90045-9. [DOI] [PubMed] [Google Scholar]
  32. Simard J., Singh S. M., Labrie F. Comparison of in vitro effects of the pure antiandrogens OH-flutamide, Casodex, and nilutamide on androgen-sensitive parameters. Urology. 1997 Apr;49(4):580–589. doi: 10.1016/s0090-4295(97)00029-0. [DOI] [PubMed] [Google Scholar]
  33. Sperry T. S., Thomas P. Characterization of two nuclear androgen receptors in Atlantic croaker: comparison of their biochemical properties and binding specificities. Endocrinology. 1999 Apr;140(4):1602–1611. doi: 10.1210/endo.140.4.6631. [DOI] [PubMed] [Google Scholar]
  34. Sperry T. S., Thomas P. Identification of two nuclear androgen receptors in kelp bass (Paralabrax clathratus) and their binding affinities for xenobiotics: comparison with Atlantic croaker (Micropogonias undulatus) androgen receptors. Biol Reprod. 1999 Oct;61(4):1152–1161. doi: 10.1095/biolreprod61.4.1152. [DOI] [PubMed] [Google Scholar]
  35. Toft G., Baatrup E. Sexual characteristics are altered by 4-tert-octylphenol and 17beta-estradiol in the adult male guppy (Poecilia reticulata). Ecotoxicol Environ Saf. 2001 Jan;48(1):76–84. doi: 10.1006/eesa.2000.1985. [DOI] [PubMed] [Google Scholar]
  36. Tyler C. R., Jobling S., Sumpter J. P. Endocrine disruption in wildlife: a critical review of the evidence. Crit Rev Toxicol. 1998 Jul;28(4):319–361. doi: 10.1080/10408449891344236. [DOI] [PubMed] [Google Scholar]
  37. Vos J. G., Dybing E., Greim H. A., Ladefoged O., Lambré C., Tarazona J. V., Brandt I., Vethaak A. D. Health effects of endocrine-disrupting chemicals on wildlife, with special reference to the European situation. Crit Rev Toxicol. 2000 Jan;30(1):71–133. doi: 10.1080/10408440091159176. [DOI] [PubMed] [Google Scholar]
  38. 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]
  39. Wolf C., Jr, Lambright C., Mann P., Price M., Cooper R. L., Ostby J., Gray L. E., Jr Administration of potentially antiandrogenic pesticides (procymidone, linuron, iprodione, chlozolinate, p,p'-DDE, and ketoconazole) and toxic substances (dibutyl- and diethylhexyl phthalate, PCB 169, and ethane dimethane sulphonate) during sexual differentiation produces diverse profiles of reproductive malformations in the male rat. Toxicol Ind Health. 1999 Jan-Mar;15(1-2):94–118. doi: 10.1177/074823379901500109. [DOI] [PubMed] [Google Scholar]
  40. Wong C., Kelce W. R., Sar M., Wilson E. M. Androgen receptor antagonist versus agonist activities of the fungicide vinclozolin relative to hydroxyflutamide. J Biol Chem. 1995 Aug 25;270(34):19998–20003. doi: 10.1074/jbc.270.34.19998. [DOI] [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES