title: Exposure to perfluoroalkyl substances and sperm DNA global methylation in Arctic and European populations.
abstract: Perfluoroalkyl substances (PFASs) are widely used in a variety of industrial processes and products, and have been detected globally in humans and wildlife. PFASs are suspected to interfere with endocrine signaling and to adversely affect human reproductive health. The aim of the present study was to investigate the associations between exposure to PFASs and sperm global methylation levels in a population of non-occupationally exposed fertile men. Measurements of PFASs in serum from 262 partners of pregnant women from Greenland, Poland and Ukraine, were also carried out by liquid chromatography tandem mass spectrometry. Perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) were detected in 97% of the blood samples. Two surrogate markers were used to assess DNA global methylation levels in semen samples from the same men: (a) average DNA methylation level in repetitive DNA sequences (Alu, LINE-1, Satα) quantified by PCR-pyrosequencing after bisulfite conversion; (b) flow cytometric immunodetection of 5-methyl-cytosines. After multivariate linear regression analysis, no major consistent associations between PFASs exposure and sperm DNA global methylation endpoints could be detected. However, since weak but statistically significant associations of different PFASs with DNA hypo- and hyper-methylation were found in some of the studied populations, effects of PFASs on sperm epigenetic processes cannot be completely excluded, and this issue warrants further investigation.
authors.affiliation: Laboratory of Toxicology, Unit of Radiation Biology and Human Health, ENEA Casaccia Research Center, Rome, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Leter
authors.forename: Claudia
authors.initials: C
authors.lastname: Consales
authors.forename: Patrizia
authors.initials: P
authors.lastname: Eleuteri
authors.forename: Raffaella
authors.initials: R
authors.lastname: Uccelli
authors.forename: Ina O
authors.initials: IO
authors.lastname: Specht
authors.forename: Gunnar
authors.initials: G
authors.lastname: Toft
authors.forename: Tania
authors.initials: T
authors.lastname: Moccia
authors.forename: Alfredo
authors.initials: A
authors.lastname: Budillon
authors.forename: Bo A G
authors.initials: BA
authors.lastname: Jönsson
authors.forename: Christian H
authors.initials: CH
authors.lastname: Lindh
authors.forename: Aleksander
authors.initials: A
authors.lastname: Giwercman
authors.forename: Henning S
authors.initials: HS
authors.lastname: Pedersen
authors.forename: Jan K
authors.initials: JK
authors.lastname: Ludwicki
authors.forename: Valentyna
authors.initials: V
authors.lastname: Zviezdai
authors.forename: Dick
authors.initials: D
authors.lastname: Heederik
authors.forename: Jens Peter E
authors.initials: JP
authors.lastname: Bonde
authors.forename: Marcello
authors.initials: M
authors.lastname: Spanò
mesh_terms: D044503:5-Methylcytosine / Q000737:chemistry; D000328:Adult; D017738:Alkanesulfonic Acids / Q000737:chemistry*; D001110:Arctic Regions; D015415:Biomarkers / Q000032:analysis; D002210:Caprylates / Q000737:chemistry*; D019175:DNA Methylation; D005227:Fatty Acids; D005466:Fluorocarbons / Q000737:chemistry*; D006116:Greenland; D006801:Humans; D008297:Male; D011044:Poland; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013094:Spermatozoa / Q000187:drug effects*; D013451:Sulfonic Acids / Q000737:chemistry*; D014455:Ukraine
chemical_list: D017738:Alkanesulfonic Acids; D015415:Biomarkers; D002210:Caprylates; D005227:Fatty Acids; D005466:Fluorocarbons; D013451:Sulfonic Acids; C471071:perfluorohexanesulfonic acid; C101816:perfluoro-n-nonanoic acid; D044503:5-Methylcytosine; C023036:perfluorooctanoic acid; C076994:perfluorooctane sulfonic acid
keywords: DNA methylation; epidemiology; flow cytometry; human spermatozoa; perfluoroalkyl substances; pyrosequencing