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Tanja Krüger,¹ Philip S. Hjelmborg,¹ Bo A.G. Jönsson,² Lars Hagmar,² Aleksander Giwercman,³ Gian-Carlo Manicardi,⁴ Davide Bizzaro,⁵ Marcello Spanò,⁶ Anna Rignell-Hydbom,² Henning S. Pedersen,⁷ Gunnar Toft,⁸ Jens Peter Bonde,⁸ and Eva C. Bonefeld-Jørgensen¹

¹Department of Environmental and Occupational Medicine, Institute of Public Health, University of Aarhus, Aarhus, Denmark; ²Department of Occupational and Environmental Medicine, University Hospital, Lund, Sweden; ³Scanian Fertility Centre, Malmö University Hospital, Malmö, Sweden; ⁴Laboratory of Genetics, Department of Agricultural Sciences, University of Modena and Reggio Emilia, Modena, Italy; ⁵Institute of Biology and Genetics, Politechnical University of Marche, Ancona, Italy; ⁶Section of Toxicology and Biomedical Sciences, BIOTEC-MED, ENEA Casaccia, Rome, Italy; ⁷Medical Centre, Dronning Ingrids Hospital, Nuuk, Greenland; ⁸Department of Occupational Medicine, Aarhus University Hospital, Aarhus, Denmark

Abstract
Background: Animal and in vitro studies have indicated that human male reproductive disorders can arise as a result of disrupted androgen receptor (AR) signalling by persistent organic pollutants (POPs) . Our aim in the present study was to compare serum xenoandrogenic activity between study groups with different POP exposures and to evaluate correlations to the POP proxy markers 2,2´,4,4´,5,5´-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis(p-chlorophenyl) -ethylene (p,p´-DDE) .

Methods: We determined xenoandrogenic activity in the serum fraction containing the lipophilic POPs but free of endogenous hormones. Adult male serum (n = 261) from Greenland, Sweden, Warsaw (Poland) , and Kharkiv (Ukraine) was analyzed. Xenoandrogenic activity was determined as the effect of serum extract alone (XAR) and in the presence of the synthetic AR agonist R1881 (XARcomp) on AR transactivated luciferase activity.

Results: The study groups differed significantly with respect to XARcomp activity, which was increased in the Inuits and decreased in the European study groups ; we observed no difference for XAR activity. We found the highest level of the AR antagonist p,p´-DDE in Kharkiv, and accordingly, this study group showed the highest percent of serum samples with decreased XARcomp activities. Furthermore, the percentage of serum samples with decreased XARcomp activities followed the p,p´-DDE serum level for the European study groups. No correlations between serum XAR or XARcomp activities and the two POP markers were revealed.

Conclusions: The differences in XARcomp serum activity between the study groups suggest differences in chemical exposure profiles, genetics, and/or lifestyle factors.

Key words: AR activity, CB-153, human serum, polychlorinated biphenyls, p, p´-DDE. Environ Health Perspect 115(suppl 1) : 21–27 (2007) . doi:10.1289/ehp.9353 available via http://dx.doi.org/ [Online 8 June 2007]

This article is part of the monograph "Endocrine Disruptors—Exposure Assessment, Novel End Points, and Low-Dose and Mixture Effects."

Address correspondence to E.C. Bonefeld-Jørgensen, Unit of Cellular and Molecular Toxicology, Department of Environmental and Occupational Medicine, Institute of Public Health, University of Aarhus, Vennelyst Blvd. 6, Building 260, DK-8000 Aarhus C., Denmark. Telephone: 045 8942 6162. Fax: +45 8942 6199. E-mail: ebj@mil.au.dk

We thank I. Sørensen, B.S. Andersen, H. Åkesson, B. Holmskov, and C. Held for technical assistance ; M. Ghisari and M. Long for scientific support ; and J.K. Ludwicki and V. Zvyezday for coordination of the blood sampling.

This study is part of the INUENDO Project supported by The European Commission (Contract no. QLK4-CT-2001-00202) . The work was also funded by the Danish Environmental Protection Agency, the Swedish Research Council, and the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning. The Ukrainian part of the study was made possible by a grant from INTAS (International Association for the Promotion of Cooperation with Scientists from the New Independent States of the Former Soviet Union ; project 012 2205) .

The authors declare they have no competing financial interests.

Received 22 May 2006 ; accepted 4 December 2006.