Pregnancy exposure to phthalates and DNA methylation in male placenta - An epigenome-wide association study.

DNA Methylation Epigenome Female Humans Male Maternal Exposure / adverse effects Phthalic Acids / metabolism Placenta / metabolism Pregnancy
Alu and LINE-1 DNA methylation Phthalates Placenta Pregnancy exposure

Journal

Environment international
ISSN: 1873-6750
Titre abrégé: Environ Int
Pays: Netherlands
ID NLM: 7807270

Informations de publication

Date de publication:
02 2022
Historique:
received: 18 08 2021
revised: 15 12 2021
accepted: 16 12 2021
pubmed: 16 1 2022
medline: 17 3 2022
entrez: 15 1 2022
Statut: ppublish

Résumé

Exposure to phthalates during pregnancy may alter DNA methylation in the placenta, a crucial organ for the growth and development of the fetus. We studied associations between urinary concentrations of phthalate biomarkers during pregnancy and placental DNA methylation. We measured concentrations of 11 phthalate metabolites in maternal spot urine samples collected between 22 and 29 gestational weeks in 202 pregnant women. We analyzed DNA methylation levels in placental tissue (fetal side) collected at delivery. We first investigated changes in global DNA methylation of repetitive elements Alu and LINE-1. We then performed an adjusted epigenome-wide association study using IlluminaHM450 BeadChips and identified differentially methylated regions (DMRs) associated with phthalate exposure. Monobenzyl phthalate concentration was inversely associated with placental methylation of Alu repeats. Moreover, all phthalate biomarkers except for monocarboxy-iso-octyl phthalate and mono(2-ethyl-5-hydroxyhexyl) phthalate were associated with at least one DMR. All but three DMRs showed increased DNA methylation with increased phthalate exposure. The largest identified DMR (22 CpGs) was positively associated with monocarboxy-iso-nonyl phthalate and encompassed heat shock proteins (HSPA1A, HSPA1L). The remaining DMRs encompassed transcription factors and nucleotide exchange factors, among other genes. This is the first description of genome-wide modifications of placental DNA methylation in association with pregnancy exposure to phthalates. Our results suggest epigenetic mechanisms by which exposure to these compounds could affect fetal development. Of interest, four identified DMRs had been previously associated with maternal smoking, which may suggest particular sensitivity of these genomic regions to the effect of environmental contaminants.

Sections du résumé

BACKGROUND
Exposure to phthalates during pregnancy may alter DNA methylation in the placenta, a crucial organ for the growth and development of the fetus.
OBJECTIVES
We studied associations between urinary concentrations of phthalate biomarkers during pregnancy and placental DNA methylation.
METHODS
We measured concentrations of 11 phthalate metabolites in maternal spot urine samples collected between 22 and 29 gestational weeks in 202 pregnant women. We analyzed DNA methylation levels in placental tissue (fetal side) collected at delivery. We first investigated changes in global DNA methylation of repetitive elements Alu and LINE-1. We then performed an adjusted epigenome-wide association study using IlluminaHM450 BeadChips and identified differentially methylated regions (DMRs) associated with phthalate exposure.
RESULTS
Monobenzyl phthalate concentration was inversely associated with placental methylation of Alu repeats. Moreover, all phthalate biomarkers except for monocarboxy-iso-octyl phthalate and mono(2-ethyl-5-hydroxyhexyl) phthalate were associated with at least one DMR. All but three DMRs showed increased DNA methylation with increased phthalate exposure. The largest identified DMR (22 CpGs) was positively associated with monocarboxy-iso-nonyl phthalate and encompassed heat shock proteins (HSPA1A, HSPA1L). The remaining DMRs encompassed transcription factors and nucleotide exchange factors, among other genes.
CONCLUSIONS
This is the first description of genome-wide modifications of placental DNA methylation in association with pregnancy exposure to phthalates. Our results suggest epigenetic mechanisms by which exposure to these compounds could affect fetal development. Of interest, four identified DMRs had been previously associated with maternal smoking, which may suggest particular sensitivity of these genomic regions to the effect of environmental contaminants.

Identifiants

DOI: 10.1016/j.envint.2021.107054 PMID: 35032864 PMC: PMC8972089
pubmed: 35032864
pii: S0160-4120(21)00679-6
doi: 10.1016/j.envint.2021.107054
pmc: PMC8972089
mid: NIHMS1791225
pii:
doi:

Substances chimiques

Phthalic Acids 0
phthalic acid 6O7F7IX66E

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

107054

Subventions

Organisme : Intramural CDC HHS
ID : CC999999
Pays : United States

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.

Références

Am J Reprod Immunol. 2009 Aug;62(2):78-89
pubmed: 19614624
Chemosphere. 2018 Sep;206:759-765
pubmed: 29793068
Genet Epidemiol. 2015 Feb;39(2):53-64
pubmed: 25537884
Curr Protoc Bioinformatics. 2016 Jun 20;54:1.30.1-1.30.33
pubmed: 27322403
Epidemiology. 2012 Mar;23(2):353-6
pubmed: 22317818
Environ Mol Mutagen. 2017 Jul;58(6):398-410
pubmed: 28556291
Bioinformatics. 2017 Apr 15;33(8):1243-1245
pubmed: 28119308
BMC Genomics. 2021 Jan 6;22(1):6
pubmed: 33407091
Toxicology. 2013 May 10;307:74-88
pubmed: 23219589
Sci Rep. 2019 Sep 10;9(1):13039
pubmed: 31506599
Environ Health Perspect. 2019 Jan;127(1):17002
pubmed: 30624098
Nucleic Acids Res. 2004 Feb 18;32(3):e38
pubmed: 14973332
Bioinformatics. 2013 Jan 15;29(2):189-96
pubmed: 23175756
Environ Mol Mutagen. 2015 Apr;56(3):286-92
pubmed: 25327576
Anal Bioanal Chem. 2005 Oct;383(4):638-44
pubmed: 16132150
Int J Toxicol. 2007 May-Jun;26(3):221-9
pubmed: 17564903
Environ Res. 2016 Nov;151:601-609
pubmed: 27596487
J Expo Sci Environ Epidemiol. 2020 Sep;30(5):835-844
pubmed: 32015430
PeerJ. 2020 Sep 15;8:e9880
pubmed: 32983644
Epigenetics. 2009 Nov 16;4(8):526-31
pubmed: 19923908
Environ Res. 2016 Jul;148:55-62
pubmed: 27019040
Hum Genet. 2012 May;131(5):747-56
pubmed: 22143225
Environ Pollut. 2021 Dec 1;290:118024
pubmed: 34523531
Bioinformatics. 2012 Nov 15;28(22):2986-8
pubmed: 22954632
Epigenomics. 2018 Jul;10(7):1011-1026
pubmed: 29957030
Genome Biol. 2017 Jan 27;18(1):19
pubmed: 28129774
Environ Health. 2012 Apr 26;11:29
pubmed: 22537080
Sci Rep. 2016 Sep 22;6:33449
pubmed: 27653773
Epidemiology. 2016 May;27(3):378-88
pubmed: 27035688
Clin Chim Acta. 2005 Nov;361(1-2):20-9
pubmed: 16004980
Front Genet. 2020 May 06;11:405
pubmed: 32435260
Environ Int. 2018 Sep;118:334-347
pubmed: 29935799
BMC Med. 2020 Oct 7;18(1):306
pubmed: 33023569
Environ Health Perspect. 2012 Jul;120(7):935-43
pubmed: 22398195
Environ Int. 2021 Jan;146:106228
pubmed: 33157377
Mol Med. 2008 Sep-Oct;14(9-10):561-6
pubmed: 18372927
Epidemiology. 2014 Sep;25(5):625-35
pubmed: 25061923
Reprod Toxicol. 2007 Jan;23(1):83-91
pubmed: 17049806
Environ Epigenet. 2018 Sep 07;4(3):dvy022
pubmed: 30210810
Bioinformatics. 2014 Feb 01;30(3):428-30
pubmed: 24336642
PLoS One. 2017 Jul 13;12(7):e0181155
pubmed: 28704530
BMC Bioinformatics. 2017 Feb 13;18(1):105
pubmed: 28193155
Stat Appl Genet Mol Biol. 2010;9:Article29
pubmed: 20812907
N Engl J Med. 2005 Oct 27;353(17):1848-50
pubmed: 16251542
Environ Res. 2014 Aug;133:396-406
pubmed: 24972507
Clin Epigenetics. 2016 Jun 21;8:70
pubmed: 27330572
Stem Cell Res Ther. 2020 Aug 6;11(1):342
pubmed: 32762732
Epigenetics. 2018;13(3):301-309
pubmed: 29513082
Front Immunol. 2016 Nov 17;7:510
pubmed: 27909437
Sci Rep. 2018 Apr 17;8(1):6086
pubmed: 29666409
Sci Rep. 2016 Feb 12;6:21004
pubmed: 26867681
Occup Environ Med. 2005 Nov;62(11):806-18
pubmed: 16234408
Nucleic Acids Res. 2016 Jan 4;44(D1):D733-45
pubmed: 26553804
Epigenetics. 2011 Nov;6(11):1284-94
pubmed: 21937876
Prenat Diagn. 2020 Aug;40(9):1193-1200
pubmed: 32010988
Environ Int. 2018 Dec;121(Pt 1):561-573
pubmed: 30300814
Genome Biol. 2013 Sep 24;14(9):r105
pubmed: 24063430
Int J Epidemiol. 2016 Apr;45(2):353-63
pubmed: 26283636
Bioinformatics. 2017 Dec 15;33(24):3982-3984
pubmed: 28961746
PLoS Genet. 2019 Aug 1;15(8):e1008236
pubmed: 31369552
Nucleic Acids Res. 2017 Feb 28;45(4):e22
pubmed: 27924034

Auteurs

Paulina Jedynak (P)

University Grenoble Alpes, Inserm, CNRS, Team of Environmental Epidemiology applied to Development and Respiratory Health, Institute for Advanced Biosciences, Grenoble, France. Electronic address: paulina.jedynak@univ-grenoble-alpes.fr.

Jörg Tost (J)

Laboratory for Epigenetics and Environment, Centre National de Recherche en Génomique Humaine, CEA - Institut de Biologie François Jacob, University Paris Saclay, Evry, France.

Antonia M Calafat (AM)

National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA.

Ekaterina Bourova-Flin (E)

University Grenoble Alpes, Inserm, CNRS, EpiMed Group, Institute for Advanced Biosciences, Grenoble, France.

Lucile Broséus (L)

University Grenoble Alpes, Inserm, CNRS, Team of Environmental Epidemiology applied to Development and Respiratory Health, Institute for Advanced Biosciences, Grenoble, France.

Florence Busato (F)

Laboratory for Epigenetics and Environment, Centre National de Recherche en Génomique Humaine, CEA - Institut de Biologie François Jacob, University Paris Saclay, Evry, France.

Anne Forhan (A)

Université de Paris, Centre for Research in Epidemiology and Statistics (CRESS), INSERM, INRAE, F-75004 Paris, France.

Barbara Heude (B)

Université de Paris, Centre for Research in Epidemiology and Statistics (CRESS), INSERM, INRAE, F-75004 Paris, France.

Milan Jakobi (M)

University Grenoble Alpes, Inserm, CNRS, Team of Environmental Epidemiology applied to Development and Respiratory Health, Institute for Advanced Biosciences, Grenoble, France.

Joel Schwartz (J)

Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Rémy Slama (R)

University Grenoble Alpes, Inserm, CNRS, Team of Environmental Epidemiology applied to Development and Respiratory Health, Institute for Advanced Biosciences, Grenoble, France.

Daniel Vaiman (D)

Genomics, Epigenetics and Physiopathology of Reproduction, Institut Cochin, U1016 Inserm - UMR 8104 CNRS - Paris-Descartes University, Paris, France.

Johanna Lepeule (J)

University Grenoble Alpes, Inserm, CNRS, Team of Environmental Epidemiology applied to Development and Respiratory Health, Institute for Advanced Biosciences, Grenoble, France. Electronic address: johanna.lepeule@univ-grenoble-alpes.fr.

Claire Philippat (C)

University Grenoble Alpes, Inserm, CNRS, Team of Environmental Epidemiology applied to Development and Respiratory Health, Institute for Advanced Biosciences, Grenoble, France.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Phénomènes génétiques › Méthylation de l'ADN › Pregnancy exposure to phthalates and DNA...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Épigénome › Pregnancy exposure to phthalates and DNA...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Pregnancy exposure to phthalates and DNA...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Pollution de l'environnement › Exposition environnementale › Exposition maternelle › Pregnancy exposure to phthalates and DNA...
questionsmedicales.fr › Composés chimiques organiques › Acides carboxyliques › Acides carbocycliques › Acides phtaliques › Pregnancy exposure to phthalates and DNA...
questionsmedicales.fr › Structures de l'embryon › Placenta › Pregnancy exposure to phthalates and DNA...
questionsmedicales.fr › Phénomènes physiologiques des appareils urinaire et reproducteur › Phénomènes physiologiques de la reproduction › Reproduction › Grossesse › Pregnancy exposure to phthalates and DNA...