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PLoS One. 2018 Feb 22;13(2):e0190698. doi: 10.1371/journal.pone.0190698. eCollection 2018.

Offspring sex impacts DNA methylation and gene expression in placentae from women with diabetes during pregnancy.

Author information

1
Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
2
Department of Pediatrics, CMRI Metabolic Research Program, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
3
Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
4
Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America.
5
Division of Neonatology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
6
Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.

Abstract

AIMS/HYPOTHESIS:

We hypothesized that diabetes during pregnancy (DDP) alters genome-wide DNA methylation in placenta resulting in differentially methylated loci of metabolically relevant genes and downstream changes in RNA and protein expression.

METHODS:

We mapped genome-wide DNA methylation with the Infinium 450K Human Methylation Bead Chip in term fetal placentae from Native American and Hispanic women with DDP using a nested case-control design (n = 17 pairs). RNA expression and protein levels were assayed via RNA-Seq and Western Blot.

RESULTS:

Genome-wide DNA methylation analysis revealed 465 CpG sites with significant changes for male offspring, 247 for female offspring, and 277 for offspring of both sexes (p<0.001). Placentae from female offspring were 40% more likely to have significant gains in DNA methylation compared with placentae from male offspring exposed to DDP (p<0.001). Changes in DNA methylation corresponded to changes in RNA and protein levels for 6 genes: PIWIL3, CYBA, GSTM1, GSTM5, KCNE1 and NXN. Differential DNA methylation was detected at loci related to mitochondrial function, DNA repair, inflammation, oxidative stress.

CONCLUSIONS/INTERPRETATION:

These findings begin to explain mechanisms responsible for the increased risk for obesity and type 2 diabetes in offspring of mothers with DDP.

PMID:
29470513
PMCID:
PMC5823368
DOI:
10.1371/journal.pone.0190698
[Indexed for MEDLINE]
Free PMC Article

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