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Tarmo Tiido,¹ Anna Rignell-Hydbom,² Bo A.G. Jönsson,² Yvonne Lundberg Giwercman,^1,3 Henning S. Pedersen,⁴ Bogdan Wojtyniak,⁵ Jan K. Ludwicki,⁶ Vladimir Lesovoy,⁷ Valentyna Zvyezday,⁸ Marcello Spano,⁹ Gian-Carlo Manicardi,¹⁰ Davide Bizzaro,¹¹ Eva C. Bonefeld-Jørgensen,¹² Gunnar Toft,¹³ Jens Peter Bonde,¹³ Lars Rylander,² Lars Hagmar,² Aleksander Giwercman,¹ and INUENDO¹³

¹Molecular Reproductive Medicine Research Unit, Department of Clinical Sciences, Fertility Centre, Malmö University Hospital, Lund University, Malmö, Sweden; ²Department of Occupational and Environmental Medicine, Lund University Hospital, Lund, Sweden; ³Department of Urology, Malmö University Hospital, Lund University, Malmö, Sweden; ⁴Centre for Arctic Environmental Medicine, Nuuk, Greenland; ⁵Department of Medical Statistics, and ⁶Department of Environmental Toxicology, National Institute of Hygiene, Warsaw, Poland; ⁷Regional Clinical Center of Urology and Nephrology, Kharkiv, Ukraine; ⁸Laboratory of Human Reproduction, Kharkiv State Medical University, Kharkiv, Ukraine; ⁹Section of Toxicology and Biomedical Sciences, BIOTEC-MED, ENEA Casaccia Research Centre, Rome, Italy; ¹⁰University of Modena and Reggio Emilia, Modena, Italy; ¹¹Istituto di Biologia e Genetica Università Politecnica delle Marche, Ancona, Italy; ¹²Institute of Public Health, Unit of Cellular and Molecular Toxicology, Department of Occupational and Environmental Medicine, University of Aarhus, Aarhus, Denmark; ¹³Department of Occupational Medicine, Aarhus University Hospital, Aarhus, Denmark

Abstract
Objective: Recent studies indicate that persistent organohalogen pollutants (POPs) may contribute to sex ratio changes in offspring of exposed populations. Our aim in the present study was to investigate whether exposure to 2,2´,4,4´,5,5´-hexachlorobiphenyl (PCB-153) and dichlorodiphenyldichloroethene (p,p´-DDE) affects sperm Y:X chromosome distribution.

Subjects and methods: We obtained semen and blood for analysis of PCB-153 and p,p´-DDE levels from 547 men from Sweden, Greenland, Poland (Warsaw) , and Ukraine (Kharkiv) , with regionally different levels of POP exposure. The proportion of Y- and X-chromosome-bearing sperm in the semen samples was determined by two-color fluorescence in situ hybridization analysis.

Results: Swedish and Greenlandic men had on average significantly higher proportions of Y sperm (in both cohorts, 51.2%) and correspondingly higher lipid-adjusted concentrations of PCB-153 (260 ng/g and 350 ng/g, respectively) compared with men from Warsaw (50.3% and 22 ng/g) and Kharkiv (50.7% and 54 ng/g) . In the Swedish cohort, log-transformed PCB-153 and log-transformed p,p´-DDE variables were significantly positively associated with Y-chromosome fractions (p-values 0.04 and < 0.001, respectively) . On the contrary, in the Polish cohort PCB-153 correlated negatively with the proportion of Y-bearing fraction of spermatozoa (p = 0.008) .

Conclusions: The present study indicates that POP exposure might be involved in changing the proportion of ejaculated Y-bearing spermatozoa in human populations. Intercountry differences, with different exposure situations and doses, may contribute to varying Y:X chromosome ratios.

Key words: polychlorinated biphenyls, POP, p, p´-DDE, sex chromosomes, sex ratio, sperm. Environ Health Perspect 114: 718-724 (2006) . doi:10.1289/ehp.8668 available via http://dx.doi.org/ [Online 29 December 2005]

Address correspondence to T. Tiido, CRC, Lund University, Building 91, Entrance 72, Floor 10, UMAS, SE 205 02 Malmö, Sweden. Telephone: 46-40-33-72-19. Fax: 46-40-33-70-43. E-mail: tarmo.tiido@med.lu.se

We thank C. Anderberg for help in fluorescence in situ hybridization analysis and K.V. Nielsen (DakoCytomation) for providing the protein-nucleic acid probes.

This work was supported by grants from the European Commission (QLK4-CT-2001-00202) ; the Swedish Research Council (grant 521-2004-6072) ; the Swedish Research Council for Environment, Agricultural Sciences, and Spatial Planning ; Swedish government funding for clinical research ; and the Crafoordska Fund.

The authors declare they have no competing financial interests.

Received 21 September 2005 ; accepted 29 December 2005.

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