title: Exposure to persistent organic pollutants and sperm DNA methylation changes in Arctic and European populations.
abstract: Persistent organic pollutants (POPs), such as PCBs (polychlorinated biphenyls) and DDT [1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane], are environmental contaminants with potential endocrine disrupting activity. DNA methylation levels in peripheral blood lymphocytes have been associated with serum concentrations of POPs in Greenland Inuit and Korean populations. Greenland Inuits are characterized by the highest worldwide POP levels. In this cross-sectional study we evaluated the relationship between serum POP concentrations and DNA methylation levels in sperm of non-occupationally exposed fertile men from Greenland, Warsaw (Poland), and Kharkiv (Ukraine). Serum levels of PCB-153 [1,2,4-trichloro-5-(2,4,5-trichlorophenyl)benzene], as a proxy of the total PCBs body burden, and of p,p'-DDE [1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene], the main metabolite of DDT were measured. Sperm DNA methylation level was assessed globally by flow cytometric (FCM) immunodetection of 5-methyl-cytosines and at specific repetitive DNA sequences (Alu, LINE-1, Satα) by PCR-pyrosequencing after bisulfite conversion. Multivariate linear regression analysis was applied to investigate correlations between serum POP concentrations and DNA methylation. No consistent associations between exposure to POPs and sperm DNA methylation at repetitive DNA sequences were detected. A statistically significant global decrease in methylation was associated with exposure to either POP by FCM analysis. This is the first study to investigate environmental exposure to POPs and DNA methylation levels considering sperm as the target cells. Although POP exposure appears to have a limited negative impact on sperm DNA methylation levels in adult males, the global hypomethylation detected by one of the methods applied suggests that further investigation is warranted.
authors.affiliation: Laboratory of Biosafety and Risk Assessment, Division of Health Technologies, Department of Sustainable Territorial and Production Systems, ENEA Casaccia Research Center, Rome, 00123, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Consales
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, DK-8200, Denmark.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Toft
authors.affiliation: Laboratory of Biosafety and Risk Assessment, Division of Health Technologies, Department of Sustainable Territorial and Production Systems, ENEA Casaccia Research Center, Rome, 00123, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Leter
authors.affiliation: Department of Occupational and Environmental Medicine, Bispebjerg University Hospital of Copenhagen, Copenhagen, NV, DK-2400, Denmark.
authors.forename: Jens Peter E
authors.initials: JP
authors.lastname: Bonde
authors.affiliation: Laboratory of Biosafety and Risk Assessment, Division of Health Technologies, Department of Sustainable Territorial and Production Systems, ENEA Casaccia Research Center, Rome, 00123, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Uccelli
authors.affiliation: Laboratory of Biosafety and Risk Assessment, Division of Health Technologies, Department of Sustainable Territorial and Production Systems, ENEA Casaccia Research Center, Rome, 00123, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Pacchierotti
authors.affiliation: Laboratory of Biosafety and Risk Assessment, Division of Health Technologies, Department of Sustainable Territorial and Production Systems, ENEA Casaccia Research Center, Rome, 00123, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Eleuteri
authors.affiliation: Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, SE-22185, Sweden.
authors.forename: Bo A G
authors.initials: BA
authors.lastname: Jönsson
authors.affiliation: Molecular Reproductive Medicine, Department of Translational Medicine, Skåne University Hospital Malmö, Lund University, Malmö, SE-20502, Sweden.
authors.forename: Aleksander
authors.initials: A
authors.lastname: Giwercman
authors.affiliation: Centre for Arctic Environmental Medicine, Greenland Institute of Natural Resources, Nuuk, Greenland, DK-3900, Denmark.
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, 00791, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Struciński
authors.affiliation: Department of Toxicology and Risk Assessment, National Institute of Public Health-National Institute of Hygiene, Warsaw, 00791, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Góralczyk
authors.affiliation: Laboratory of Human Reproduction, Department of Social Medicine and Organization of Public Health, Kharkiv National Medical University, Kharkiv, 61022, Ukraine.
authors.forename: Valentyna
authors.initials: V
authors.lastname: Zviezdai
authors.affiliation: Laboratory of Biosafety and Risk Assessment, Division of Health Technologies, Department of Sustainable Territorial and Production Systems, ENEA Casaccia Research Center, Rome, 00123, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Spanò
mesh_terms: D000328:Adult; D020087:Alu Elements; D003634:DDT / Q000633:toxicity; D019175:DNA Methylation / Q000187:drug effects*; D003633:Dichlorodiphenyl Dichloroethylene / Q000097:blood / Q000633:toxicity; D004781:Environmental Exposure / Q000009:adverse effects* / Q000032:analysis; D004785:Environmental Pollutants / Q000097:blood / Q000633:toxicity*; D044127:Epigenesis, Genetic / Q000187:drug effects; D006116:Greenland; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D008297:Male; D011044:Poland; D011078:Polychlorinated Biphenyls / Q000097:blood / Q000633:toxicity; D013094:Spermatozoa / Q000187:drug effects* / Q000502:physiology; D014455:Ukraine
chemical_list: D004785:Environmental Pollutants; D003633:Dichlorodiphenyl Dichloroethylene; D003634:DDT; D011078:Polychlorinated Biphenyls; C014024:2,4,5,2',4',5'-hexachlorobiphenyl
keywords: epidemiology; epigenetics; human spermatozoa; p,p′-DDT [1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane]; polychlorinated biphenyls (PCBs)