title: Phthalates, perfluoroalkyl acids, metals and organochlorines and reproductive function: a multipollutant assessment in Greenlandic, Polish and Ukrainian men.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: Virissa
authors.initials: V
authors.lastname: Lenters
authors.affiliation: Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: Lützen
authors.initials: L
authors.lastname: Portengen
authors.affiliation: Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: Lidwien A M
authors.identifier: http://orcid.org/0000-0003-0292-0946
authors.initials: LA
authors.lastname: Smit
authors.affiliation: Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
authors.forename: Bo A G
authors.initials: BA
authors.lastname: Jönsson
authors.affiliation: Reproductive Medicine Centre, Skåne University Hospital Malmö, Lund University, Malmö, Sweden.
authors.forename: Aleksander
authors.initials: A
authors.lastname: Giwercman
authors.affiliation: Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Rylander
authors.affiliation: Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
authors.forename: Christian H
authors.initials: CH
authors.lastname: Lindh
authors.affiliation: Laboratory of Toxicology, Unit of Radiation Biology and Human Health, ENEA Casaccia Research Center, Rome, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Spanò
authors.affiliation: Centre for Arctic Environmental Medicine, Nuuk, Greenland.
authors.forename: Henning S
authors.initials: HS
authors.lastname: Pedersen
authors.affiliation: Department of Toxicology and Risk Assessment, National Institute of Public Health-National Institute of Hygiene, Warsaw, Poland.
authors.forename: Jan K
authors.initials: JK
authors.lastname: Ludwicki
authors.affiliation: Department of Social Medicine and Organization of Public Health, Kharkiv National Medical University, Kharkiv, Ukraine.
authors.forename: Lyubov
authors.initials: L
authors.lastname: Chumak
authors.affiliation: Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Aldert H
authors.initials: AH
authors.lastname: Piersma
authors.affiliation: Department of Occupational Medicine, Danish Ramazzini Center, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Toft
authors.affiliation: Department of Occupational and Environmental Medicine, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens Peter
authors.initials: JP
authors.lastname: Bonde
authors.affiliation: Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: Dick
authors.initials: D
authors.lastname: Heederik
authors.affiliation: Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: Roel
authors.initials: R
authors.lastname: Vermeulen
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D004781:Environmental Exposure / Q000009:adverse effects*; D004785:Environmental Pollutants / Q000097:blood / Q000633:toxicity; D042341:Gonadal Hormones / Q000097:blood*; D006116:Greenland; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000097:blood / Q000633:toxicity; D008297:Male; D008670:Metals / Q000097:blood / Q000633:toxicity; D010795:Phthalic Acids / Q000097:blood / Q000633:toxicity; D011044:Poland; D012044:Regression Analysis; D012098:Reproduction / Q000187:drug effects*; D055101:Semen Analysis; D013081:Sperm Motility / Q000187:drug effects; D014455:Ukraine; D055815:Young Adult
chemical_list: D015415:Biomarkers; D004785:Environmental Pollutants; D042341:Gonadal Hormones; D006843:Hydrocarbons, Chlorinated; D008670:Metals; D010795:Phthalic Acids
keywords: environmental pollutants; partial least squares; reproductive health; sex hormones; variable selection