Prenatal exposure to phthalates and peripheral blood and buccal epithelial DNA methylation in infants: An epigenome-wide association study.

DNA Methylation Epigenome Female Fetal Blood / chemistry Humans Infant Infant, Newborn Phthalic Acids Placenta / metabolism Pregnancy Prenatal Exposure Delayed Effects / genetics
450K APrON study DNA methylation Epigenetics Neurodevelopment Phthalates

Journal

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

Informations de publication

Date de publication:
05 2022
Historique:
received: 17 12 2021
revised: 16 02 2022
accepted: 09 03 2022
pubmed: 25 3 2022
medline: 27 4 2022
entrez: 24 3 2022
Statut: ppublish

Résumé

Prenatal exposure to phthalates has been associated with adverse health and neurodevelopmental outcomes. DNA methylation (DNAm) alterations may be a mechanism underlying these effects, but prior investigations of prenatal exposure to phthalates and neonatal DNAm profiles are limited to placental tissue and umbilical cord blood. Conduct an epigenome-wide association study (EWAS) of the associations between prenatal exposure to phthalates and DNAm in two accessible infant tissues, venous buffy coat blood and buccal epithelial cells (BECs). Participants included 152 maternal-infant pairs from the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Maternal second trimester urine samples were analyzed for nine phthalate metabolites. Blood (n = 74) or BECs (n = 78) were collected from 3-month-old infants and profiled for DNAm using the Infinium HumanMethylation450 (450K) BeadChip. Robust linear regressions were used to investigate the associations between high (HMWPs) and low molecular weight phthalates (LMWPs) and change in methylation levels at variable Cytosine-phosphate-Guanine (CpG) sites in infant tissues, as well as the sensitivity of associations to potential confounders. One candidate CpG in gene RNF39 reported by a previous study examining prenatal exposure to phthalates and cord blood DNAm was replicated. The EWAS identified 12 high-confidence CpGs in blood and another 12 in BECs associated with HMWPs and/or LMWPs. Prenatal exposure to bisphenol A (BPA) associated with two of the CpGs associated with HMWPs in BECs. Prenatal exposure to phthalates was associated with DNAm variation at CpGs annotated to genes associated with endocrine hormone activity (i.e., SLCO4A1, TPO), immune pathways and DNA damage (i.e., RASGEF1B, KAZN, HLA-A, MYO18A, DIP2C, C1or109), and neurodevelopment (i.e., AMPH, NOTCH3, DNAJC5). Future studies that characterize the stability of these associations in larger samples, multiple cohorts, across tissues, and investigate the potential associations between these biomarkers and relevant health and neurodevelopmental outcomes are needed.

Sections du résumé

BACKGROUND
Prenatal exposure to phthalates has been associated with adverse health and neurodevelopmental outcomes. DNA methylation (DNAm) alterations may be a mechanism underlying these effects, but prior investigations of prenatal exposure to phthalates and neonatal DNAm profiles are limited to placental tissue and umbilical cord blood.
OBJECTIVE
Conduct an epigenome-wide association study (EWAS) of the associations between prenatal exposure to phthalates and DNAm in two accessible infant tissues, venous buffy coat blood and buccal epithelial cells (BECs).
METHODS
Participants included 152 maternal-infant pairs from the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Maternal second trimester urine samples were analyzed for nine phthalate metabolites. Blood (n = 74) or BECs (n = 78) were collected from 3-month-old infants and profiled for DNAm using the Infinium HumanMethylation450 (450K) BeadChip. Robust linear regressions were used to investigate the associations between high (HMWPs) and low molecular weight phthalates (LMWPs) and change in methylation levels at variable Cytosine-phosphate-Guanine (CpG) sites in infant tissues, as well as the sensitivity of associations to potential confounders.
RESULTS
One candidate CpG in gene RNF39 reported by a previous study examining prenatal exposure to phthalates and cord blood DNAm was replicated. The EWAS identified 12 high-confidence CpGs in blood and another 12 in BECs associated with HMWPs and/or LMWPs. Prenatal exposure to bisphenol A (BPA) associated with two of the CpGs associated with HMWPs in BECs.
DISCUSSION
Prenatal exposure to phthalates was associated with DNAm variation at CpGs annotated to genes associated with endocrine hormone activity (i.e., SLCO4A1, TPO), immune pathways and DNA damage (i.e., RASGEF1B, KAZN, HLA-A, MYO18A, DIP2C, C1or109), and neurodevelopment (i.e., AMPH, NOTCH3, DNAJC5). Future studies that characterize the stability of these associations in larger samples, multiple cohorts, across tissues, and investigate the potential associations between these biomarkers and relevant health and neurodevelopmental outcomes are needed.

Identifiants

DOI: 10.1016/j.envint.2022.107183 PMID: 35325772
pubmed: 35325772
pii: S0160-4120(22)00109-X
doi: 10.1016/j.envint.2022.107183
pii:
doi:

Substances chimiques

Phthalic Acids 0
phthalic acid 6O7F7IX66E

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

107183

Subventions

Organisme : NIEHS NIH HHS
ID : R21 ES021295
Pays : United States
Organisme : CIHR
ID : MOP-201003
Pays : Canada
Organisme : CIHR
ID : MOP-201203
Pays : Canada
Organisme : CIHR
ID : PG-201909
Pays : Canada

Informations de copyright

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

Auteurs

Gillian England-Mason (G)

Department of Paediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Owerko Centre, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.

Sarah M Merrill (SM)

Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; Centre for Molecular Medicine and Therapeutics, Vancouver, British Columbia, Canada.

Nicole Gladish (N)

Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; Centre for Molecular Medicine and Therapeutics, Vancouver, British Columbia, Canada.

Sarah R Moore (SR)

Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; Centre for Molecular Medicine and Therapeutics, Vancouver, British Columbia, Canada.

Gerald F Giesbrecht (GF)

Department of Paediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Owerko Centre, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada; Department of Psychology, Faculty of Arts, University of Calgary, Calgary, Alberta, Canada; Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

Nicole Letourneau (N)

Department of Paediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Owerko Centre, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada; Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Faculty of Nursing, University of Calgary, Calgary, Alberta, Canada; Department of Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, Calgary, Alberta, Canada.

Julia L MacIsaac (JL)

Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; Centre for Molecular Medicine and Therapeutics, Vancouver, British Columbia, Canada.

Amy M MacDonald (AM)

Alberta Centre for Toxicology, University of Calgary, Calgary, Alberta, Canada.

David W Kinniburgh (DW)

Alberta Centre for Toxicology, University of Calgary, Calgary, Alberta, Canada; Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada.

Anne-Louise Ponsonby (AL)

Murdoch Children's Research Institute, Royal Children's Hospital, University of Melbourne, Melbourne, Victoria, Australia.

Richard Saffery (R)

Murdoch Children's Research Institute, Royal Children's Hospital, University of Melbourne, Melbourne, Victoria, Australia.

Jonathan W Martin (JW)

Science for Life Laboratory, Department of Environmental Science, Stockholm University, Stockholm, Södermanland, Sweden.

Michael S Kobor (MS)

Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; Centre for Molecular Medicine and Therapeutics, Vancouver, British Columbia, Canada; Program in Child and Brain Development, CIFAR, Toronto, Ontario, Canada.

Deborah Dewey (D)

Department of Paediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Owerko Centre, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada; Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, Calgary, Alberta, Canada. Electronic address: dmdewey@ucalgary.ca.

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Classifications MeSH

questionsmedicales.fr › Phénomènes génétiques › Méthylation de l'ADN › Prenatal exposure to phthalates and peripheral...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Épigénome › Prenatal exposure to phthalates and peripheral...
questionsmedicales.fr › Structures de l'embryon › Foetus › Sang foetal › Prenatal exposure to phthalates and peripheral...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Prenatal exposure to phthalates and peripheral...
questionsmedicales.fr › Personnes › Tranches d'âge › Nourrisson › Prenatal exposure to phthalates and peripheral...
questionsmedicales.fr › Personnes › Tranches d'âge › Nourrisson › Nouveau-né › Prenatal exposure to phthalates and peripheral...
questionsmedicales.fr › Composés chimiques organiques › Acides carboxyliques › Acides carbocycliques › Acides phtaliques › Prenatal exposure to phthalates and peripheral...
questionsmedicales.fr › Structures de l'embryon › Placenta › Prenatal exposure to phthalates and peripheral...
questionsmedicales.fr › Phénomènes physiologiques des appareils urinaire et reproducteur › Phénomènes physiologiques de la reproduction › Reproduction › Grossesse › Prenatal exposure to phthalates and peripheral...
questionsmedicales.fr › Maladies urogénitales › Maladies de l'appareil urogénital féminin et complications de la grossesse › Complications de la grossesse › Lésions prénatales › Effets différés de l'exposition prénatale à des facteurs de risque › Prenatal exposure to phthalates and peripheral...