Exposure to Gestational Diabetes Enriches Immune-Related Pathways in the Transcriptome and Methylome of Human Amniocytes.
Adult
Amniotic Fluid
/ cytology
Birth Weight
/ genetics
Case-Control Studies
Chromatin
/ metabolism
CpG Islands
/ genetics
DNA Methylation
Diabetes, Gestational
/ metabolism
Epigenesis, Genetic
/ immunology
Epigenome
Female
Gestational Age
Humans
Infant, Newborn
Interferons
/ immunology
Male
Maternal Age
Obesity
/ genetics
Pregnancy
Pregnancy Trimester, Second
Prenatal Exposure Delayed Effects
/ genetics
RNA-Seq
Sex Factors
Signal Transduction
/ genetics
Transcriptome
DNA methylation
epigenetics
fetal programming
gestational diabetes
immune activation
interferon
Journal
The Journal of clinical endocrinology and metabolism
ISSN: 1945-7197
Titre abrégé: J Clin Endocrinol Metab
Pays: United States
ID NLM: 0375362
Informations de publication
Date de publication:
01 10 2020
01 10 2020
Historique:
received:
14
04
2020
accepted:
15
07
2020
pubmed:
21
7
2020
medline:
20
2
2021
entrez:
21
7
2020
Statut:
ppublish
Résumé
Gestational diabetes (GDM) has profound effects on the intrauterine metabolic milieu and is linked to obesity and diabetes in offspring, but the mechanisms driving these effects remain largely unknown. Alterations in DNA methylation and gene expression in amniocytes exposed to GDM in utero represent a potential mechanism leading to metabolic dysfunction later in life. To profile changes in genome-wide DNA methylation and expression in human amniocytes exposed to GDM. A nested case-control study (n = 14 pairs) was performed in amniocytes matched for offspring sex, maternal race/ethnicity, maternal age, gestational age at amniocentesis, and gestational age at birth. Sex-specific genome-wide DNA methylation analysis and RNA-sequencing were completed and differentially methylated regions (DMRs) and gene expression changes were identified. Ingenuity pathway analysis identified biologically relevant pathways enriched after GDM exposure. In silico high-throughput chromosome conformation capture (Hi-C) analysis identified potential chromatin interactions with DMRs. Expression of interferon-stimulated genes was increased in GDM amniocytes, accounting for 6 of the top 10 altered genes (q < 0.05). Enriched biological pathways in GDM amniocytes included pathways involving inflammation, the interferon response, fatty liver disease, monogenic diabetes, and atherosclerosis. Forty-two DMRs were identified in male GDM-exposed amniocytes and 20 in female amniocyte analysis (q < 0.05). Hi-C analysis identified interactions between DMRs and 11 genes with significant expression changes in male amniocytes and 9 in female amniocytes (P < .05). In a unique repository of human amniocytes exposed to GDM in utero, transcriptome analysis identified enrichment of inflammation and interferon-related pathways and novel DMRs with potential distal regulatory functions.
Identifiants
pubmed: 32687192
pii: 5873862
doi: 10.1210/clinem/dgaa466
pmc: PMC7451504
pii:
doi:
Substances chimiques
Chromatin
0
Interferons
9008-11-1
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
Subventions
Organisme : NIDDK NIH HHS
ID : K08 DK090302
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES013508
Pays : United States
Organisme : NIEHS NIH HHS
ID : R21 ES011675
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001878
Pays : United States
Informations de copyright
© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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