Ecotoxicology

, Volume 11, Issue 6, pp 423–434

Window of Sensitivity for the Estrogenic Effects of Ethinylestradiol in Early Life-Stages of Fathead Minnow, Pimephales promelas

  • Ronny van Aerle
  • Nadine Pounds
  • Tom H. Hutchinson
  • Sue Maddix
  • Charles R. Tyler
Article

Abstract

Sexual differentiation in fish occurs after hatching during early life-stages and is believed to be a time when the gonad has a heightened sensitivity to disruption by chemicals that mimic hormones. In this study fathead minnows (Pimephales promelas) were exposed to an environmentally relevant concentration of ethinylestradiol (EE2) for short intervals in fish early life-stages and vitellogenic and gonadal responses were measured at 30 and 100 dph (sexual maturity), respectively. All EE2 exposure regimes induced vitellogenin (VTG) synthesis and disruption in duct development (a feminization) in males, with a window of enhanced sensitivity between 10 and 15 dph (where 60% of the males had feminized ducts). There was an altered pattern in sex cell development in males (inhibition of spermatogenesis) in the solvent controls (ethanol 0.1 ml/l) and all EE2 treatments when compared with the dilution water controls. Furthermore, fewer spermatozoa were observed in the testis of males exposed to EE2 from 15 to 20 dph and fertilized eggs (<24 h post-fertilization)-20 dph, compared with both the solvent and dilution water controls. These data show that short exposures of embryos/very early life-stage fathead minnows to an environmentally relevant concentration of EE2 lead to alterations in gonadal development that potentially have reproductive consequences and thus population level effects.

Ethinylestradiol Gonadal ducts Vitellogenin Fish Endocrine disruption 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aherne, G.W. and Briggs, R. (1989). The relavence of the presence of certain synthetic steroids in the aquatic environment. J. Pharm. Pharmacol. 41, 735–6.Google Scholar
  2. Conover, D.O. and Kynard, B.E. (1981). Environmental sex determination — interaction of temperature and genotype in a fish. Science 213, 577–9.Google Scholar
  3. Desbrow, C., Routledge, E.J., Brighty, G.C., Sumpter, J.P. and Waldock, M. (1998). Identification of estrogenic chemicals in stw effluent. 1. Chemical fractionation and in vitro biological screening. Environ. Sci. Technol. 32, 1549–58.Google Scholar
  4. Flouriot, G., Pakdel, F., Ducouret, B. and Valotaire, Y. (1995). Influence of xenobiotics on rainbow trout liver estrogen receptor and vitellogenin gene expression. J. Mol. Endocrinol. 15, 143–51.Google Scholar
  5. Folmar, L.C., Hemmer, M., Hemmer, R., Bowman, C., Kroll, K. and Denslow, N.D. (2000). Comparative estrogenicity of estradiol, ethynyl estradiol and diethylstilbestrol in an in vivo, male sheepshead minnow (Cyprinodon variegatus), vitellogenin bioassay. Aquat. Toxicol. 49, 77–88.Google Scholar
  6. Gimeno, S., Komen, H., Venderbosch, P.W.M. and Bowmer, T. (1997). Disruption of sexual differentiation in genetic male common carp (Cyprinus carpio) exposed to an alkylphenol during different life stages. Environ. Sci. Technol. 31, 2884–90.Google Scholar
  7. Gimeno, S., Komen, H., Gerritsen, A.G.M. and Bowmer, T. (1998). Feminisation of young males of the common carp, Cyprinus carpio, exposed to 4-tert-pentylphenol during sexual differentiation. Aquat. Toxicol. 43, 77–92.Google Scholar
  8. Gray, M.A. and Metcalfe, C.D. (1997). Induction of testis-ova in Japanese medaka (Oryzias latipes) exposed to p-nonylphenol. Environ. Toxicol. Chem. 16, 1082–6.Google Scholar
  9. Gray, M.A. and Metcalfe, C.D. (1999). Toxicity of 4-tertoctylphenol to early life stages of Japanese medaka (Oryzias latipes). Aquat. Toxicol. 46, 149–54.Google Scholar
  10. Harries, J.E., Sheahan, D.A., Jobling, S., Matthiessen, P., Neall, P., Routledge, E.J., Rycroft, R., Sumpter, J.P. and Tylor, T. (1996). A survey of estrogenic activity in United Kingdom inland waters. Environ. Toxicol. Chem. 15, 1993–2002.Google Scholar
  11. Harries, J.E., Runnalls, T., Hill, E., Harris, C.A., Maddix, S., Sumpter, J.P. and Tyler, C.R. (2000). Development of a reproductive performance test for endocrine disrupting chemicals using pair-breeding fathead minnows (Pimephales promelas). Environ. Sci. Technol. 34, 3003–11.Google Scholar
  12. Harris, C., Santos, E.M., Pottinger, T.G., Tyler, C.R. and Sumpter, J.P. (2001). Exposure to 4 tert-nonylphenol alters gonadotrophin dynamics in the pituitary and plasma of female rainbow trout (Oncorhynchus mykiss). Environ. Sci. Technol. 35, 2909–16.Google Scholar
  13. Herman, R.L. and Kincaid, H.L. (1988). Pathological effects of orally administered estradiol to rainbow trout. Aquaculture 72, 165–72.Google Scholar
  14. Iwamatsu, T. (1999). Convenient method for sex reversal in a freshwater teleost, the medaka. J. Exp. Zool. 283, 210–14.Google Scholar
  15. Jobling, S., Sheahan, D., Osborne, J.A., Matthiessen, P. and Sumpter, J.P. (1996). Inhibition of testicular growth in rainbow trout (Oncorhynchus mykiss) exposed to estrogenic alkylphenolic chemicals. Environ. Toxicol. Chem. 15, 194–202.Google Scholar
  16. Jobling, S., Nolan, M., Tyler, C.R., Brighty, G. and Sumpter, J.P. (1998). Widespread sexual disruption in wild fish. Environ. Sci. Technol. 32, 2498–506.Google Scholar
  17. Jobling, S., Beresford, N., Nolan, M., Rodgers-Gray, T., Brighty, G.C., Sumpter, J.P. and Tyler, C.R. (2002). Altered sexual maturation and gamete production in wild roach (Rutilus rutilus) living in rivers that receive treated sewage effluents. Biol. Reprod. 66, 272–81.Google Scholar
  18. Lange, R., Hutchinson, T.H., Croudace, C.P., Siegmund, F., Schweinfurth, H., Hampe, P., Panter, G.H. and Sumpter, J.P. (2001). Effects of the synthetic estrogen 17 alpha-ethinylestradiol on the life-cycle of the fathead minnow (Pimephales promelas). Environ. Toxicol. Chem. 20, 1216–27.Google Scholar
  19. Larsson, D.G.J., Adolfsson-Erici, M., Parkkonen, J., Pettersson, M., Berg, A.H., Olsson, P.E. and Forlin, L. (1999). Ethinyloestradiol—an undesired fish contraceptive? Aquat. Toxicol. 45, 91–7.Google Scholar
  20. McKim, J.M., Nichols, J.W., Lien, G.J., Hoffman, A.D., Gallinat, C.A. and Stokes, G.N. (1996). Dermal absorption of three waterborne chloroethanes in rainbow trout (Oncorhynchus mykiss) and channel catfish (Ictalurus punctatus). Fundam. Appl. Toxicol. 31, 218–28.Google Scholar
  21. Nakamura, M. and Takahashi, H. (1973). Gonadal sex differentiation in tilapia mossambica, with special regard to the time of estrogen treatment effective in inducing complete feminization of genetic males. Bull. Fac. Fish Hokkaido Univ. 24, 1–13.Google Scholar
  22. Nakamura, M. (1978). Morphological and Experimental Studies on Sex Differentiation of the Gonad in Several Teleost Fishes. Hokkaido, Japan: Hokkaido University.Google Scholar
  23. Nakamura, M. (1984). Effects of estradiol-17β on gonadal sex differentiation in two species of salmonids, the masu salmon, Oncorhynchus masou, and the chum salmon, O. keta. Aquaculture 43, 83–90.Google Scholar
  24. Nimrod, A.C. and Benson, W.H. (1998). Reproduction and development of japanese medaka following an early life stage exposure to xenoestrogens. Aquat. Toxicol. 44, 141–56.Google Scholar
  25. Nolan, M., Jobling, S., Brighty, G., Sumpter, J.P. and Tyler, C.R. (2001). A histological description of intersexuality in the roach. J. Fish Biol. 58, 160–76.Google Scholar
  26. Pandian, T.J. and Sheela, S.G. (1995). Hormonal induction of sex reversal in fish. Aquaculture 138, 1–22.Google Scholar
  27. Panter, G.H., Thompson, R.S. and Sumpter, J.P. (1998). Adverse reproductive effects in male fathead minnows (Pimephales promelas) exposed to environmentally relevant concentrations of the natural oestrogens, oestradiol and oestrone. Aquat. Toxicol. 42, 243–53.Google Scholar
  28. Parks, L.G., Cheek, A.O., Denslow, N.D., Heppell, S.A., McLachlan, J.A., LeBlanc, G.A. and Sullivan, C.V. (1999). Fathead minnow (Pimephales promelas) vitellogenin: Purification, characterization and quantitative immunoassay for the detection of estrogenic compounds. Comp. Biochem. Physiol. C — Pharmacol. Toxicol. Endocrinol. 123, 113–25.Google Scholar
  29. Patino, R., Davis, K.B., Schoore, J.E., Uguz, C., Strussmann, C.A., Parker, N.C., Simco, B.A. and Goudie, C.A. (1996). Sex differentiation of channel catfish gonads: Normal development and effects of temperature. J. Exp. Zool. 276, 209–18.Google Scholar
  30. Pifferer, F., Benfey, T.J. and Donaldson, E.M. (1994). Gonadal morphology of normal and sex-reversed triploid and gynogenetic diploid coho salmon (Oncorhynchus kisutch). J. Fish Biol. 45, 541–53.Google Scholar
  31. Rodgers-Gray, T.P., Jobling, S., Morris, S., Kelly, C., Kirby, S., Janbakhsh, A., Harries, J.E., Waldock, M.J., Sumpter, J.P. and Tyler, C.R. (2000). Long-term temporal changes in the estrogenic composition of treated sewage effluent and its biological effects on fish. Environ. Sci. Technol. 34, 1521–8.Google Scholar
  32. Rodgers-Gray, T.P., Jobling, S., Kelly, C., Morris, S., Brighty, G., Waldock, M.J., Sumpter, J.P. and Tyler, C.R. (2001). Exposure of juvenile roach (Rutilus rutilus) to treated sewage effluent induces dose-dependent and persistent disruption in gonadal duct development. Environ. Sci. Technol. 35, 462–70.Google Scholar
  33. Routledge, E.J., Sheahan, D., Desbrow, C., Brighty, G.C., Waldock, M. and Sumpter, J.P. (1998). Identification of estrogenic chemicals in STW effluent. 2. In vivo responses in trout and roach. Environ. Sci. Technol. 32, 1559–65.Google Scholar
  34. Scholz, S. and Gutzeit, H.O. (2000). 17-alpha-ethinylestradiol affects reproduction, sexual differentiation and aromatase gene expression of the medaka (Oryzias latipes). Aquat. Toxicol. 50, 363–73.Google Scholar
  35. Schwaiger, J., Spieser, O.H., Bauer, C., Ferling, H., Mallow, U., Kalbfus, W. and Negele, R.D. (2000). Chronic toxicity of nonylphenol and ethinylestradiol: Haematological and histopathological effects in juvenile common carp (Cyprinus carpio). Aquat. Toxicol. 51, 69–78.Google Scholar
  36. Shibata, N. and Hamaguchi, S. (1988). Evidence for the sexual bipotentiality of spermatogonia in the fish, Oryzias latipes. J. Exp. Zool. 245, 71–7.Google Scholar
  37. Shore, L.S. (1993). Estrogen as an environmental pollutant. Bull. Environ. Contam. Toxicol. 51, 361–6.Google Scholar
  38. Sohoni, P., Tyler, C.R., Toy, R., Caunter, J., Kurd, K., Hetheridge, M., Williams, T., Evans, M., Gargas, E. and Sumpter, J.P. (2001). Reproductive effects of long term (2 generation) exposure to Bisphenol A in the fathead minnow (Pimephales promelas). Environ. Sci. Technol. 35, 2917–25.Google Scholar
  39. Strussmann, C.A. and Takashima, F. and Toda, K. (1996). Sex-differentiation and hormonal feminization in pejerrey Odontesthes bonariensis. Aquaculture 139, 31–45.Google Scholar
  40. Thorpe, K., Hetheridge, M., Hutchinson, T.H., Scholze, M., Sumpter, J.P. and Tyler, C.R. (2001b). Assessing the biological potency of binary mixtures of environmental estrogens using vitellogenin induction in juvenile rainbow trout (Oncorhynchus mykiss). Environ. Sci. Technol. 35, 2476–81.Google Scholar
  41. Thorpe, K.L., Hutchinson, T.H., Hetheridge, M.J., Sumpter, J.P. and Tyler, C.R. (2000). Development of an in vivo screening assay for estrogenic chemicals using juvenile rainbow trout (Oncorhynchus mykiss). Environ. Toxicol. Chem. 19, 2812–20.Google Scholar
  42. Thorpe, K.L., Cummings, R.I., Hutchinson, T.H., Scholze, M., Brighty, G., Sumpter, J.P. and Tyler, C.R. (2001a). Relative potencies and additive effects of steroidal estrogens in fish. Environ. Sci. Technol. (Submitted).Google Scholar
  43. Tyler, C.R., Jobling, S. and Sumpter, J.P. (1998). Endocrine disruption in wildlife: A critical review of the evidence. Crit. Rev. Toxicol. 28, 319–61.Google Scholar
  44. Tyler, C.R. and Routledge, E.J. (1998). Oestrogenic effects in fish in English rivers with evidence of their causation. Pure Appl. Chem. 70, 1795–804.Google Scholar
  45. Tyler, C.R., van Aerle, R., Hutchinson, T.H., Maddix, S. and Trip, H. (1999). An in vivo testing system for endocrine disruptors in fish early life stages using induction of vitellogenin. Environ. Toxicol. Chem. 18, 337–47.Google Scholar
  46. van Aerle, R., Runnalls, T.J. and Tyler, C.R. (2000). Gonadal sex differentiation in fathead minnow, Pimephales promelas. 4th International Symposium on Fish Endocrinology, Washington, Seattle: USA.Google Scholar
  47. van Aerle, R., Nolan, M., Jobling, S., Christiansen, L.B., Sumpter, J.P. and Tyler, C.R. (2001). Sexual disruption in a second species of wild cyprinid fish (the gudgeon, Gobio gobio) in UK fresh waters. Environ. Toxicol. Chem. 20, 2841–7.Google Scholar
  48. Wester, P.W. and Canton, J.H. (1986). Histopathological study of Oryzias latipes (medaka) after long term β-hexachlorocyclohexane exposure. Aquat. Toxicol. 9, 21–45.Google Scholar
  49. Yamamoto, T. (1953). Artificially induced sex-reversal in genotypic male medaka (Oryzias latipes). J. Exp. Zool. 123, 571–94.Google Scholar
  50. Yamazaki, F. (1983). Sex control and manipulation of fish. Aquaculture 33, 329–54.Google Scholar
  51. Zillioux, E.J., Johnson, I.C., Kiparissis, Y., Metcalfe, C.D., Wheat, J.V., Ward, S.G. and Liu, H. (2001). The sheepshead minnow as an in vivo model for endocrine disruption in marine teleosts: A partial life-cycle test with 17α-ethynylestradiol. Environ. Toxicol. Chem. 20, 1968–78Google Scholar

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Ronny van Aerle
    • 1
  • Nadine Pounds
    • 2
  • Tom H. Hutchinson
    • 2
  • Sue Maddix
    • 3
  • Charles R. Tyler
    • 1
  1. 1.Environmental and Molecular Fish Biology Group, Hatherly Laboratories, School of Biological SciencesUniversity of ExeterExeterUK
  2. 2.Brixham Environmental LaboratoryAstraZeneca, United KingdomBrixhamDevon, UK
  3. 3.Department of Biological SciencesBrunel UniversityUxbridge, MiddlesexUK

Personalised recommendations