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Phthalates, perfluoroalkyl acids, metals and organochlorines and reproductive function: a multipollutant assessment in Greenlandic, Polish and Ukrainian men
  1. Virissa Lenters1,
  2. Lützen Portengen1,
  3. Lidwien A M Smit1,
  4. Bo A G Jönsson2,
  5. Aleksander Giwercman3,
  6. Lars Rylander2,
  7. Christian H Lindh2,
  8. Marcello Spanò4,
  9. Henning S Pedersen5,
  10. Jan K Ludwicki6,
  11. Lyubov Chumak7,
  12. Aldert H Piersma8,
  13. Gunnar Toft9,
  14. Jens Peter Bonde10,
  15. Dick Heederik1,
  16. Roel Vermeulen1
  1. 1Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands
  2. 2Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden
  3. 3Reproductive Medicine Centre, Skåne University Hospital Malmö, Lund University, Malmö, Sweden
  4. 4Laboratory of Toxicology, Unit of Radiation Biology and Human Health, ENEA Casaccia Research Center, Rome, Italy
  5. 5Centre for Arctic Environmental Medicine, Nuuk, Greenland
  6. 6Department of Toxicology and Risk Assessment, National Institute of Public Health-National Institute of Hygiene, Warsaw, Poland
  7. 7Department of Social Medicine and Organization of Public Health, Kharkiv National Medical University, Kharkiv, Ukraine
  8. 8Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
  9. 9Department of Occupational Medicine, Danish Ramazzini Center, Aarhus University Hospital, Aarhus, Denmark
  10. 10Department of Occupational and Environmental Medicine, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark
  1. Correspondence to Dr Roel Vermeulen, Institute for Risk Assessment Sciences, Utrecht University, P.O. Box 80.178, Utrecht 3508 TD, The Netherlands; R.C.H.Vermeulen{at}


Objectives Numerous environmental contaminants have been linked to adverse reproductive health outcomes. However, the complex correlation structure of exposures and multiple testing issues limit the interpretation of existing evidence. Our objective was to identify, from a large set of contaminant exposures, exposure profiles associated with biomarkers of male reproductive function.

Methods In this cross-sectional study (n=602), male partners of pregnant women were enrolled between 2002 and 2004 during antenatal care visits in Greenland, Poland and Ukraine. Fifteen contaminants were detected in more than 70% of blood samples, including metabolites of di(2-ethylhexyl) and diisononyl phthalates (DEHP, DiNP), perfluoroalkyl acids, metals and organochlorines. Twenty-two reproductive biomarkers were assessed, including serum levels of reproductive hormones, markers of semen quality, sperm chromatin integrity, epididymal and accessory sex gland function, and Y:X chromosome ratio. We evaluated multipollutant models with sparse partial least squares (sPLS) regression, a simultaneous dimension reduction and variable selection approach which accommodates joint modelling of correlated exposures.

Results Of the over 300 exposure–outcome associations tested in sPLS models, we detected 10 associations encompassing 8 outcomes. Several associations were notably consistent in direction across the three study populations: positive associations between mercury and inhibin B, and between cadmium and testosterone; and inverse associations between DiNP metabolites and testosterone, between polychlorinated biphenyl-153 and progressive sperm motility, and between a DEHP metabolite and neutral α-glucosidase, a marker of epididymal function.

Conclusions This global assessment of a mixture of environmental contaminants provides further indications that some organochlorines and phthalates adversely affect some parameters of male reproductive health.

  • environmental pollutants
  • partial least squares
  • reproductive health
  • sex hormones
  • variable selection

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