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Jens Peter Bonde,¹ Gunnar Toft,¹ Lars Rylander,² Anna Rignell-Hydbom,² Aleksander Giwercman,³ Marcello Spano,⁴ Gian Carlo Manicardi,⁵ Davide Bizzaro,⁶ Jan K. Ludwicki,⁷ Valentina Zvyezday,⁸ Eva C. Bonefeld-Jørgensen,⁹ Henning Sloth Pedersen,¹⁰ Bo A.G. Jönsson,² Ane Marie Thulstrup,¹ and INUENDO^11,*

¹Department of Occupational Medicine, Åarhus University Hospital, Århus, Denmark; ²Division of Occupational and Environmental Medicine and Psychiatric Epidemiology, Lund University Hospital, Lund, Sweden; ³Reproductive Medicine Center, Lund University, Malmö University Hospital, Malmö, Sweden; ⁴Section of Toxicology and Biomedical Sciences, BAS-BIOTEC-MED, ENEA Casaccia, Rome, Italy; ⁵University of Modena and Reggio Emilia, Modena, Italy; ⁶Institute of Biology and Genetics, Politechnical University of Marche, Ancona, Italy; ⁷Department of Environmental Toxicology, National Institute of Hygiene, Warsaw, Poland; ⁸Kharkiv State Medical University, Kharkiv, Ukraine; ⁹Institute of Public Health, Department of Occupational and Environmental Medicine, University of Aarhus, Århus, Denmark; ¹⁰Centre for Arctic Environmental Medicine, Nuuk, Greenland; ¹¹http://www.inuendo.dk

Abstract
Objective: We synthesized the main findings from an international epidemiologic study on the impact of biopersistent organic pollutants (POPs) on human reproductive function.

Data sources and extraction: We used a database with interview and biological data from 2,269 women and their spouses, and 18 published core papers.

Data synthesis: The study did not provide direct evidence of hormone-like activity of the polychlorinated biphenyl (PCB) congener CB-153 and the main dichlorodiphenyltrichloroethane (DDT) metabolite, 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (p,p´-DDE) , as serum concentrations of these compounds were not consistently related to either endogenous or exogenous hormone activity in serum. Nevertheless several links bewteen POP exposure and biomarkers of male reproductive function were identified. First, an association between high CB-153 serum levels and low sperm counts was detected within a subgroup of men with short androgen receptor CAG repeat length. Second, a relationship between increased CB-153 serum concentrations and decreased sperm motility was seen in all four studied regions, and indications of reduced neutral α-glucosidase activity in seminal plasma point to a post-testicular effect. Third, damage of sperm chromatin integrity was considerably less frequent in Greenlandic Inuits compared with that in European groups, and only in the latter was impairment of sperm chromatin integrity related to POPs. Despite these effects, fertility in terms of time taken to conceive was not related to POPs except in Inuits. A likely explanation of the latter was not identified.

Conclusions: POPs may interfere with male reproductive function without major impact on fertility. The data do not provide direct evidence for endocrine disruption, hence other mechanisms should also be considered.

Key words: Inuit, polymorphisms, reproductive health, semen quality, sex hormone receptors, time to pregnancy, xenobiotics. Environ Health Perspect 116:269–277 (2008) . doi:10.1289/ehp.10700 available via http://dx.doi.org/ [Online 23 November 2007]

Address correspondence to J.P. Bonde, Department of Occupational Medicine, Åarhus University Hospital, Nørrebrogade 44, Build. 2C, 8000 Åarhus C, Denmark. Telephone: 45 8949 4291. Fax: 45 8949 4260. E-mail: jpbon@as.aaa.dk

*INUENDO (INUit-ENDOcrine) is the acronym for "Biopersistent organochlorines in diet and human fertility. Epidemiological studies in time to pregnancy and semen quality in Inuit and European populations."

The study was supported by grants from the EU Fifth Framework Programme (QLK4-CT-2001-00202) , INTAS (2001 2205) , Århus University Hospital, the Swedish Medical Research Council, the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning, and the Danish Environmental Protection Agency.

The authors declare they have no competing financial interests.

Received 23 July 2007 ; accepted 23 November 2007.

Correction

Figure 2C was incorrect in the manuscript originally published online and has now been replaced with the corrrect version.