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Willem Dhooge,¹ Nicolas van Larebeke,² Gudrun Koppen,³ Vera Nelen,⁴ Greet Schoeters,³ Robert Vlietinck,⁵ Jean-Marc Kaufman,¹ and Frank Comhaire,¹ for the Flemish Environment and Health Study Group*

¹Department of Endocrinology, University Hospital Ghent, Belgium; ²Study Centre for Carcinogenesis and Primary Prevention of Cancer, Department of Radiotherapy, Nuclear Medicine and Experimental Cancerology, University Hospital Ghent, Belgium; ³Flemish Institute of Technological Research (VITO), Centre of Expertise in Environmental Toxicology, Mol, Belgium; ⁴Provincial Institute for Hygiene, Antwerp, Belgium; ⁵Department of Human Heredity, Catholic University of Leuven, Leuven, Belgium

Abstract
Background: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and some related environmental contaminants are aryl hydrocarbon receptor (AhR) ligands that exert reproductive and developmental toxicity in laboratory animals. In humans, fertility-related effects are less documented.

Objective: The aim of this study was to investigate the relationship between dioxin-like biological activity in serum and parameters of reproductive status in men from the general population 5 months after a polychlorinated biphenyl and dioxin food-contamination episode in Belgium.

Design: In the framework of the cross-sectional Flemish Environment and Health Study (FLEHS) , we recruited 101 men 20–40 years of age and evaluated sperm parameters, measured sex hormones, and gathered information on a number of lifestyle factors. In addition, we determined the AhR-mediated enzymatic response elicited by individual serum samples and expressed it as TCDD equivalent concentrations (CALUX-TEQs) using an established transactivation assay.

Results: Age (p = 0.04) and the frequency of fish (p = 0.02) and egg (p = 0.001) consumption were independent positive determinants of serum dioxin-like activity. After correcting for possible confounders, we found that a 2-fold increase in CALUX-TEQ > 16 pg/L was associated with a 7.1% and 6.8% (both p = 0.04) decrease in total and free testosterone, respectively. We also observed a more pronounced drop in semen volume of 16.0% (p = 0.03) , whereas sperm concentration rose by 25.2% (p = 0.07) . No relationship was found with total sperm count or sperm morphology.

Conclusions: These data suggest an interaction of dioxin-like compounds with the secretory function of the seminal vesicles or prostate, possibly indirectly through an effect on testosterone secretion, at levels not affecting spermatogenesis as such.

Key words: dioxin, DR-CALUX, egg consumption, hormones, male fertility, semen volume, sperm concentration, TCDD, testosterone. Environ Health Perspect 114: 1670–1676 (2006) . doi:10.1289/ehp.9224 available via http://dx.doi.org/ [Online 27 July 2006]

Address correspondence to W. Dhooge, Department of Endocrinology, University Hospital Ghent, 185 De Pintelaan, B9000 Ghent, Belgium. Telephone: 32 9 241 80 46. Fax: 32 9 241 80 40. E-mail: Willem@Dhooge.org

*F. Buntinx, S. Callens, E. Den Hond, R. Fagard, T. Nawrot, L. Thijs, J.A. Staessen, D. Vanderschueren, E. Van Hecke, H. Van Loon, and M.K. Viaene (Catholic University of Leuven, Leuven, Belgium) ; T. De Ceuster, E. Goelen, R. Van Den Heuvel, G. Verheyen, and L. Verschaeve [Flemish Institute of Technological Research (VITO) , Mol, Belgium] ; I. Loots, M. Herremans, P. Mertens, P. Vermeire, and J. Weyler (University of Antwerp, Antwerp, Belgium) ; and H.A. Roels (Université catholique de Louvain, Brussels, Belgium) .

We thank G. Thys, C. Van Turnhout, M.P. Lommaert, N. Benoy, R. Danckers, L. Thijs, and I. Calders for assistance with fieldwork ; N. De Clercq and S. Stuyvaert for their expert technical help in semen and hormone analysis ; and D. De Bacquer for reviewing the statistics of the article and for providing helpful comments.

The Flemish Environment and Health Study was commissioned and financed by the Ministry of the Flemish Community (Department of Science, Brussels, Belgium) . W.D. was supported by a fund from the Support Group Environment and Health, financed by the Flemish Government (Department of Science, Department of Public Health and Department of Environment, Brussels, Belgium) .

The authors declare they have no competing financial interests.