title: Effects of prenatal perfluoroalkyl acid exposure on cord blood IGF2/H19 methylation and ponderal index: The Hokkaido Study.
abstract: Prenatal exposure to perfluoroalkyl acids (PFAAs) influences fetal growth and long-term health. However, whether PFAAs affect offspring DNA methylation patterns to influence health outcomes is yet to be evaluated. Here, we assessed effect of prenatal PFAA exposure on cord blood insulin-like growth factor 2 (IGF2), H19, and long interspersed element 1 (LINE1) methylation and its associations with birth size. Mother-child pairs (N=177) from the Hokkaido Study on Environment and Children's Health were included in the study. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) levels in maternal serum were measured by liquid chromatography-tandem mass spectrometry. IGF2, H19, and LINE1 methylation in cord blood DNA was determined by pyrosequencing. After full adjustment in multiple linear regression models, IGF2 methylation showed a significant negative association with log-unit increase in PFOA (partial regression coefficient=-0.73; 95% confidence interval: -1.44 to -0.02). Mediation analysis suggested that reduced IGF2 methylation explained ~21% of the observed association between PFOA exposure and reduced ponderal index of the infant at birth. These results indicated that the effects of prenatal PFOA exposure could be mediated through DNA methylation. Further study will be required to determine the potential for long-term adverse health effects of reduced IGF2 methylation induced by PFOA exposure.
authors.affiliation: Center for Environmental and Health Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kobayashi
authors.affiliation: Center for Environmental and Health Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Azumi
authors.affiliation: Center for Environmental and Health Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Houman
authors.initials: H
authors.lastname: Goudarzi
authors.affiliation: Center for Environmental and Health Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Araki
authors.affiliation: Center for Environmental and Health Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Miyashita
authors.affiliation: Center for Environmental and Health Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Sumitaka
authors.initials: S
authors.lastname: Kobayashi
authors.affiliation: Center for Environmental and Health Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Itoh
authors.affiliation: Department of Public Health Sciences, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Seiko
authors.initials: S
authors.lastname: Sasaki
authors.affiliation: Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ishizuka
authors.affiliation: Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakazawa
authors.affiliation: Center for Environmental and Health Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Tamiko
authors.initials: T
authors.lastname: Ikeno
authors.affiliation: Center for Environmental and Health Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Kishi
mesh_terms: D000328:Adult; D017738:Alkanesulfonic Acids / Q000009:adverse effects / Q000097:blood; D001724:Birth Weight; D002210:Caprylates / Q000009:adverse effects* / Q000097:blood; D002853:Chromatography, Liquid; D015331:Cohort Studies; D019175:DNA Methylation / Q000187:drug effects*; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005317:Fetal Growth Retardation / Q000139:chemically induced*; D005466:Fluorocarbons / Q000009:adverse effects* / Q000097:blood; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D007564:Japan; D016014:Linear Models; D020084:Long Interspersed Nucleotide Elements; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced*; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D017738:Alkanesulfonic Acids; D002210:Caprylates; D005466:Fluorocarbons; D007335:Insulin-Like Growth Factor II; C023036:perfluorooctanoic acid; C076994:perfluorooctane sulfonic acid