Skip to main content
PMC home page
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 2003 Sep;111(12):1448–1453. doi: 10.1289/ehp.6139

Clustering of sex hormone disruptors in Singapore's marine environment.

Yinhan Gong 1, Hong Soon Chin 1, Lis Sa Elissa Lim 1, Chong Jin Loy 1, Jeffrey P Obbard 1, E L Yong 1
PMCID: PMC1241645  PMID: 12948882

Abstract

Abnormal sexual differentiation and other reproductive abnormalities in marine animals indicate the presence in seawater of endocrine-disrupting compounds (EDCs) that perturb the function of the sex hormone signaling pathways. However, most studies to date have reported on EDC effects in freshwater and sewage samples, and there is a paucity of bioassay data on the effects of EDCs in marine waters. Our aims in this study were to devise robust methodologies suitable for extracting potential EDCs and to measure their summated effects on activities of androgen receptors (ARs) and estrogen receptors (ER-alpha and ER-beta) in marine samples from Singapore's coastal waters. In this study, we examined the ability of C18, hydrophilic and lipophilic balance, and diol cartridges to extract potential EDCs from seawater samples. Extracts from C18 cartridges exhibited the highest sex hormone bioactivities in reporter gene assays based on a human cell line expressing AR, ER-alpha, and ER-beta. Examination of extracts from 20 coastal locations showed high androgenic and estrogenic agonist activities in confined clusters closest to the main island of Singapore. Sex hormone activity declined rapidly in clusters farther from the main coastline and in more open waters. Unexpectedly, surface and mid-depth samples from the confined high-activity clusters, in the presence of hormone, exhibited AR and ER-alpha activities that were 200-900% higher than those observed for the cognate hormone alone. This enhanced sex hormone activity suggests that analyses of complex seawater mixtures may uncover unusual bioactivities that may not be obvious by studying individual compounds. Our data present a "snapshot" of the sex hormone disruptor activity in Singapore's marine environment and indicate that C18 extraction for EDCs used in conjunction with reporter gene bioassays represents a robust and sensitive methodology for measuring summated androgenic and estrogenic activities in seawater.

Full Text

The Full Text of this article is available as a PDF (254.8 KB).

Selected References

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

  1. Baatrup E., Junge M. Antiandrogenic pesticides disrupt sexual characteristics in the adult male guppy Poecilia reticulata. Environ Health Perspect. 2001 Oct;109(10):1063–1070. doi: 10.1289/ehp.011091063. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Basheer C., Tan K. S., Lee H. K. Organotin and Irgarol-1051 contamination in Singapore coastal waters. Mar Pollut Bull. 2002 Jul;44(7):697–703. doi: 10.1016/s0025-326x(01)00330-7. [DOI] [PubMed] [Google Scholar]
  3. Bester K., Theobald N., Schröder H. F. Nonylphenols, nonylphenol-ethoxylates, linear alkylbenzenesulfonates (LAS) and bis (4-chlorophenyl)-sulfone in the German Bight of the North Sea. Chemosphere. 2001 Nov;45(6-7):817–826. doi: 10.1016/s0045-6535(01)00023-6. [DOI] [PubMed] [Google Scholar]
  4. Booij K., van Drooge B. L. Polychlorinated biphenyls and hexachlorobenzene in atmosphere, sea-surface microlayer, and water measured with semi-permeable membrane devices (SPMDs). Chemosphere. 2001 Jul;44(2):91–98. doi: 10.1016/s0045-6535(00)00303-9. [DOI] [PubMed] [Google Scholar]
  5. Carpenter David O., Arcaro Kathleen, Spink David C. Understanding the human health effects of chemical mixtures. Environ Health Perspect. 2002 Feb;110 (Suppl 1):25–42. doi: 10.1289/ehp.02110s125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. De Guise S., Shaw S. D., Barclay J. S., Brock J., Brouwer A., Dewailly E., Fair P. A., Fournier M., Grandjean P., Guillette L. J., Jr Consensus statement: Atlantic Coast Contaminants Workshop 2000. Environ Health Perspect. 2001 Dec;109(12):1301–1302. doi: 10.1289/ehp.011091301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dinan L., Bourne P., Whiting P., Dhadialla T. S., Hutchinson T. H. Screening of environmental contaminants for ecdysteroid agonist and antagonist activity using the Drosophila melanogaster B(II) cell in vitro assay. Environ Toxicol Chem. 2001 Sep;20(9):2038–2046. doi: 10.1897/1551-5028(2001)020<2038:soecfe>2.0.co;2. [DOI] [PubMed] [Google Scholar]
  8. Enmark E., Gustafsson J. A. Nyupptäckt östrogenreceptor. Oppnar nya behandlingsmöjligheter vid postklimakteriella symtom, osteoporos, ateroskleros, bröst- och prostatacancer. Lakartidningen. 1998 Apr 22;95(17):1945–1949. [PubMed] [Google Scholar]
  9. Fossi M. C., Casini S., Ancora S., Moscatelli A., Ausili A., Notarbartolo-di-Sciara G. Do endocrine disrupting chemicals threaten Mediterranean swordfish? Preliminary results of vitellogenin and Zona radiata proteins in Xiphias gladius. Mar Environ Res. 2001 Dec;52(5):477–483. doi: 10.1016/s0141-1136(01)00107-6. [DOI] [PubMed] [Google Scholar]
  10. García-Reyero N., Grau E., Castillo M., López de Alda M. J., Barceló D., Piña B. Monitoring of endocrine disruptors in surface waters by the yeast recombinant assay. Environ Toxicol Chem. 2001 Jun;20(6):1152–1158. doi: 10.1897/1551-5028(2001)020<1152:moedis>2.0.co;2. [DOI] [PubMed] [Google Scholar]
  11. Gercken Jens, Sordyl Holmer. Intersex in feral marine and freshwater fish from northeastern Germany. Mar Environ Res. 2002 Sep-Dec;54(3-5):651–655. doi: 10.1016/s0141-1136(02)00156-3. [DOI] [PubMed] [Google Scholar]
  12. Gómez-Gutiérrez J., Palomares-García R., Hernández-Trujillo S., Carballido-Carranza A. Community structure of zooplankton in the main entrance of Bahía Magdalena, México during 1996. Rev Biol Trop. 2001 Jun;49(2):545–557. [PubMed] [Google Scholar]
  13. Hashimoto S., Bessho H., Hara A., Nakamura M., Iguchi T., Fujita K. Elevated serum vitellogenin levels and gonadal abnormalities in wild male flounder (Pleuronectes yokohamae) from Tokyo Bay, Japan. Mar Environ Res. 2000 Feb;49(1):37–53. doi: 10.1016/s0141-1136(99)00047-1. [DOI] [PubMed] [Google Scholar]
  14. Hotchkiss A. K., Ostby J. S., Vandenburgh J. G., Gray L. E., Jr Androgens and environmental antiandrogens affect reproductive development and play behavior in the Sprague-Dawley rat. Environ Health Perspect. 2002 Jun;110 (Suppl 3):435–439. doi: 10.1289/ehp.02110s3435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Keith T. L., Snyder S. A., Naylor C. G., Staples C. A., Summer C., Kannan K., Giesy J. P. Identification and quantitation of nonylphenol ethoxylates and nonylphenol in fish tissues from Michigan. Environ Sci Technol. 2001 Jan 1;35(1):10–13. [PubMed] [Google Scholar]
  16. Knap Anthony, Dewailly Eric, Furgal Chris, Galvin Jennifer, Baden Dan, Bowen Robert E., Depledge Michael, Duguay Linda, Fleming Lora E., Ford Tim. Indicators of ocean health and human health: developing a research and monitoring framework. Environ Health Perspect. 2002 Sep;110(9):839–845. doi: 10.1289/ehp.02110839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Knap Anthony, Dewailly Eric, Furgal Chris, Galvin Jennifer, Baden Dan, Bowen Robert E., Depledge Michael, Duguay Linda, Fleming Lora E., Ford Tim. Indicators of ocean health and human health: developing a research and monitoring framework. Environ Health Perspect. 2002 Sep;110(9):839–845. doi: 10.1289/ehp.02110839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Larsson D. G. Joakim, Förlin Lars. Male-biased sex ratios of fish embryos near a pulp mill: temporary recovery after a short-term shutdown. Environ Health Perspect. 2002 Aug;110(8):739–742. doi: 10.1289/ehp.02110739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Li N., Lee H. K. Solid-phase extraction of polycyclic aromatic hydrocarbons in surface water. Negative effect of humic acid. J Chromatogr A. 2001 Jul 6;921(2):255–263. doi: 10.1016/s0021-9673(01)00879-2. [DOI] [PubMed] [Google Scholar]
  20. Loy C. J., Yong E. L. Sex, infertility and the molecular biology of the androgen receptor. Curr Opin Obstet Gynecol. 2001 Jun;13(3):315–321. doi: 10.1097/00001703-200106000-00012. [DOI] [PubMed] [Google Scholar]
  21. Matthiessen Peter, Allen Yvonne, Bamber Shaw, Craft John, Hurst Mark, Hutchinson Tom, Feist Steve, Katsiadaki Ioanna, Kirby Mark, Robinson Craig. The impact of oestrogenic and androgenic contamination on marine organisms in the United Kingdom--summary of the EDMAR programme. Endocrine Disruption in the Marine Environment. Mar Environ Res. 2002 Sep-Dec;54(3-5):645–649. doi: 10.1016/s0141-1136(02)00135-6. [DOI] [PubMed] [Google Scholar]
  22. Melnick Ronald, Lucier George, Wolfe Mary, Hall Roxanne, Stancel George, Prins Gail, Gallo Michael, Reuhl Kenneth, Ho Shuk-Mei, Brown Terry. Summary of the National Toxicology Program's report of the endocrine disruptors low-dose peer review. Environ Health Perspect. 2002 Apr;110(4):427–431. doi: 10.1289/ehp.02110427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Murk Albertinka J., Legler Juliette, van Lipzig Marola M. H., Meerman John H. N., Belfroid Angelique C., Spenkelink Albertus, van der Burg Bart, Rijs Gerard B. J., Vethaak Dick. Detection of estrogenic potency in wastewater and surface water with three in vitro bioassays. Environ Toxicol Chem. 2002 Jan;21(1):16–23. [PubMed] [Google Scholar]
  24. Omoto Y., Kobayashi Y., Nishida K., Tsuchiya E., Eguchi H., Nakagawa K., Ishikawa Y., Yamori T., Iwase H., Fujii Y. Expression, function, and clinical implications of the estrogen receptor beta in human lung cancers. Biochem Biophys Res Commun. 2001 Jul 13;285(2):340–347. doi: 10.1006/bbrc.2001.5158. [DOI] [PubMed] [Google Scholar]
  25. Rajapakse Nissanka, Silva Elisabete, Kortenkamp Andreas. Combining xenoestrogens at levels below individual no-observed-effect concentrations dramatically enhances steroid hormone action. Environ Health Perspect. 2002 Sep;110(9):917–921. doi: 10.1289/ehp.02110917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Safe S., Connor K., Ramamoorthy K., Gaido K., Maness S. Human exposure to endocrine-active chemicals: hazard assessment problems. Regul Toxicol Pharmacol. 1997 Aug;26(1 Pt 1):52–58. doi: 10.1006/rtph.1997.1118. [DOI] [PubMed] [Google Scholar]
  27. Scheffer G. J., Broekmans F. J. M., Looman C. W. N., Blankenstein M., Fauser B. C. J. M., teJong F. H., teVelde E. R. The number of antral follicles in normal women with proven fertility is the best reflection of reproductive age. Hum Reprod. 2003 Apr;18(4):700–706. doi: 10.1093/humrep/deg135. [DOI] [PubMed] [Google Scholar]
  28. Schiff Kenneth C., Weisberg Stephen B., Raco-Rands Valerie. Inventory of ocean monitoring in the Southern California Bight. Environ Manage. 2002 Jun;29(6):871–876. doi: 10.1007/s00267-001-2628-9. [DOI] [PubMed] [Google Scholar]
  29. Simons S. S., Jr Environmental estrogens: can two "alrights" make a wrong? Science. 1996 Jun 7;272(5267):1451–1451. doi: 10.1126/science.272.5267.1451. [DOI] [PubMed] [Google Scholar]
  30. Takao T., Nanamiya W., Nagano I., Asaba K., Kawabata K., Hashimoto K. Exposure with the environmental estrogen bisphenol A disrupts the male reproductive tract in young mice. Life Sci. 1999;65(22):2351–2357. doi: 10.1016/s0024-3205(99)00502-0. [DOI] [PubMed] [Google Scholar]
  31. Takeyoshi Masahiro, Yamasaki Kanji, Sawaki Masakuni, Nakai Makoto, Noda Shuji, Takatsuki Mineo. The efficacy of endocrine disruptor screening tests in detecting anti-estrogenic effects downstream of receptor-ligand interactions. Toxicol Lett. 2002 Jan 25;126(2):91–98. doi: 10.1016/s0378-4274(01)00446-5. [DOI] [PubMed] [Google Scholar]
  32. Tanabe Shinsuke. Contamination and toxic effects of persistent endocrine disrupters in marine mammals and birds. Mar Pollut Bull. 2002;45(1-12):69–77. doi: 10.1016/s0025-326x(02)00175-3. [DOI] [PubMed] [Google Scholar]
  33. Tillmann M., Schulte-Oehlmann U., Duft M., Markert B., Oehlmann J. Effects of endocrine disruptors on prosobranch snails (Mollusca: Gastropoda) in the laboratory. Part III: Cyproterone acetate and vinclozolin as antiandrogens. Ecotoxicology. 2001 Dec;10(6):373–388. doi: 10.1023/a:1012279231373. [DOI] [PubMed] [Google Scholar]
  34. Wang Q., Lu J., Yong E. L. Ligand- and coactivator-mediated transactivation function (AF2) of the androgen receptor ligand-binding domain is inhibited by the cognate hinge region. J Biol Chem. 2000 Dec 1;276(10):7493–7499. doi: 10.1074/jbc.M009916200. [DOI] [PubMed] [Google Scholar]
  35. Zeng Eddy Y., Tran Kim. Distribution of chlorinated hydrocarbons in overlying water, sediment, polychaete, and hornyhead turbot (Pleuronichthys verticalis) in the coastal ocean, Southern California, USA. Environ Toxicol Chem. 2002 Aug;21(8):1600–1608. [PubMed] [Google Scholar]

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

RESOURCES