title: Interactions between polymorphisms in the aryl hydrocarbon receptor signalling pathway and exposure to persistent organochlorine pollutants affect human semen quality.
abstract: Persistent organic pollutants (POPs) may affect male reproductive function. Many dioxin-like POPs exert their effects by activation of the aryl hydrocarbon receptor (AHR) signalling pathway. We analysed whether gene-environment interactions between polymorphisms in AHR (R554K) and AHR repressor (AHRR P185A) and serum levels of markers of POP exposure 1,1-bis-(4-chlorophenyl)-2,2-dichloroethene (p,p'-DDE) and 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) are associated with 21 parameters of male reproductive function in 581 proven-fertile European and Greenlandic men. In Greenlandic men, AHR variants significantly modified the association between serum levels of both p,p'-DDE and CB-153 and inhibin B levels, sperm chromatin integrity, and seminal zinc levels. In the total cohort, interactions between AHRR variants and serum levels of CB-153 were associated with sperm chromatin integrity and the expression of the pro-apoptotic marker protein Fas. The data indicate that susceptibility to adverse effects of POP exposure on male reproductive function is dependent on polymorphisms in genes involved in AHR signalling.
authors.affiliation: Department of Clinical Sciences Malmö, Molecular Reproductive Medicine, Lund University, SE-20502 Malmö, Sweden. Electronic address: leon.brokken@med.lu.se.
authors.forename: L J S
authors.initials: LJ
authors.lastname: Brokken
authors.affiliation: Department of Clinical Sciences Malmö, Molecular Reproductive Medicine, Lund University, SE-20502 Malmö, Sweden.
authors.forename: P J
authors.initials: PJ
authors.lastname: Lundberg
authors.affiliation: Laboratory of Toxicology, Unit of Radiation Biology and Human Health, ENEA Casaccia Research Centre, Via Anguillarese 301, IT-00123 Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Spanò
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, IT-41125 Reggio Emilia, Italy.
authors.forename: G C
authors.initials: GC
authors.lastname: Manicardi
authors.affiliation: Centre for Arctic Environmental Medicine, DK-3900 Nuuk, Greenland.
authors.forename: H S
authors.initials: HS
authors.lastname: Pedersen
authors.affiliation: Department of Toxicology and Risk Assessment, National Institute of Public Health - National Institute of Hygiene, PL-00791 Warsaw, Poland.
authors.forename: P
authors.initials: P
authors.lastname: Struciński
authors.affiliation: Department of Toxicology and Risk Assessment, National Institute of Public Health - National Institute of Hygiene, PL-00791 Warsaw, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Góralczyk
authors.affiliation: Social Medicine and Organization of Public Health, Kharkiv National Medical University, UA-61022 Kharkiv, Ukraine.
authors.forename: V
authors.initials: V
authors.lastname: Zviezdai
authors.affiliation: Division of Occupational and Environmental Medicine, Lund University, SE-22185 Lund, Sweden.
authors.forename: B A G
authors.initials: BA
authors.lastname: Jönsson
authors.affiliation: Department of Occupational and Environmental Medicine, Copenhagen University Hospital, DK-2400 Copenhagen, Denmark.
authors.forename: J P
authors.initials: JP
authors.lastname: Bonde
authors.affiliation: Danish Ramazzini Centre, Department of Occupational Medicine, Aarhus University Hospital, DK-8000 Aarhus, Denmark.
authors.forename: G
authors.initials: G
authors.lastname: Toft
authors.affiliation: Department of Clinical Sciences Malmö, Molecular Genetic Reproductive Medicine, Lund University, SE-20502, Malmö, Sweden.
authors.forename: Y
authors.initials: Y
authors.lastname: Lundberg Giwercman
authors.affiliation: Department of Clinical Sciences Malmö, Molecular Reproductive Medicine, Lund University, SE-20502 Malmö, Sweden; Reproductive Medicine Centre, Skåne University Hospital, SE-20502, Malmö, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Giwercman
mesh_terms: D000328:Adult; D053938:DNA Fragmentation / Q000187:drug effects; D003633:Dichlorodiphenyl Dichloroethylene / Q000633:toxicity; D004781:Environmental Exposure / Q000009:adverse effects; D004785:Environmental Pollutants / Q000633:toxicity; D006801:Humans; D007265:Inhibins / Q000097:blood; D008297:Male; D011078:Polychlorinated Biphenyls / Q000633:toxicity; D020641:Polymorphism, Single Nucleotide; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics; D012661:Semen / Q000187:drug effects; D055101:Semen Analysis; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D013094:Spermatozoa / Q000187:drug effects
chemical_list: D004785:Environmental Pollutants; D018336:Receptors, Aryl Hydrocarbon; D012097:Repressor Proteins; C422364:inhibin B; D003633:Dichlorodiphenyl Dichloroethylene; D007265:Inhibins; D011078:Polychlorinated Biphenyls; C014024:2,4,5,2',4',5'-hexachlorobiphenyl
keywords: Aryl hydrocarbon receptor; Aryl hydrocarbon receptor repressor; Cross-sectional studies; DNA damage; Genetic association studies; Gene–environment interaction; Single nucleotide polymorphism