DNA methylation profiles in the blood of newborn term infants born to mothers with obesity.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2022
2022
Historique:
received:
11
01
2022
accepted:
19
04
2022
entrez:
2
5
2022
pubmed:
3
5
2022
medline:
6
5
2022
Statut:
epublish
Résumé
Maternal obesity is an important risk factor for childhood obesity and influences the prevalence of metabolic diseases in offspring. As childhood obesity is influenced by postnatal factors, it is critical to determine whether children born to women with obesity during pregnancy show alterations that are detectable at birth. Epigenetic mechanisms such as DNA methylation modifications have been proposed to mediate prenatal programming. We investigated DNA methylation signatures in male and female infants from mothers with a normal Body Mass Index (BMI 18.5-24.9 kg/m2) compared to mothers with obesity (BMI≥30 kg/m2). BMI was measured during the first prenatal visit from women recruited into the Ontario Birth Study (OBS) at Mount Sinai Hospital in Toronto, ON, Canada. DNA was extracted from neonatal dried blood spots collected from heel pricks obtained 24 hours after birth at term (total n = 40) from women with a normal BMI and women with obesity matched for parity, age, and neonatal sex. Reduced representation bisulfite sequencing was used to identify genomic loci associated with differentially methylated regions (DMRs) in CpG-dense regions most likely to influence gene regulation. DMRs were predominantly localized to intergenic regions and gene bodies, with only 9% of DMRs localized to promoter regions. Genes associated with DMRs were compared to those from a large publicly available cohort study, the Avon Longitudinal Study of Parents and Children (ALSPAC; total n = 859). Hypergeometric tests revealed a significant overlap in genes associated with DMRs in the OBS and ALSPAC cohorts. PTPRN2, a gene involved in insulin secretion, and MAD1L1, which plays a role in the cell cycle and tumor suppression, contained DMRs in males and females in both cohorts. In males, KEGG pathway analysis revealed significant overrepresentation of genes involved in endocytosis and pathways in cancer, including IGF1R, which was previously shown to respond to diet-induced metabolic stress in animal models and in lymphocytes in the context of childhood obesity. These preliminary findings are consistent with Developmental Origins of Health and Disease paradigm, which posits that adverse prenatal exposures set developmental health trajectories.
Identifiants
pubmed: 35500004
doi: 10.1371/journal.pone.0267946
pii: PONE-D-22-00978
pmc: PMC9060365
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0267946Subventions
Organisme : Medical Research Council
ID : MC_PC_19009
Pays : United Kingdom
Organisme : NICHD NIH HHS
ID : R01 HD068437
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_12013/8
Pays : United Kingdom
Organisme : CIHR
ID : FDN-148368
Pays : Canada
Organisme : Medical Research Council
ID : MC_PC_15018
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12013/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G9815508
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/I025263/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 102215/2/13/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12013/2
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBI025751/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 076467/Z/05/Z
Pays : United Kingdom
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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