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

PloS One
Jacqueline AlexanderSara E Pinney

Abstract

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. 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. 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. These findings begin to explain mechanisms responsible for the increased risk for obesity and type 2 diabetes in offspr...Continue Reading

References

May 1, 1985·Annals of Human Genetics·S LindsayR A Flavell
Feb 3, 1983·The New England Journal of Medicine·D J PettittW C Knowler
Sep 1, 1993·Genes & Development·M S BartolomeiS M Tilghman
Jul 5, 2002·Journal of Vascular Research·Marie JirkovskáPetr Karen
Aug 9, 2003·Genomics·Takashi SasakiNobuyoshi Shimizu
Oct 6, 2004·Genome Biology·Robert C GentlemanJianhua Zhang
Apr 12, 2005·Annual Review of Pharmacology and Toxicology·John D HayesIan R Jowsey
Jul 22, 2005·Current Diabetes Reports·Xinhua Chen, Theresa O Scholl
Mar 28, 2006·Diabetes Research and Clinical Practice·Fabio SgarbosaMarilza V C Rudge
Jan 9, 2007·Lipids in Health and Disease·Danik M MartirosyanVladimir I Zoloedov
Jul 22, 2008·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Xiaodong ZhaoChia-Lin Wei
Sep 5, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Bridget R Mueller, Tracy L Bale
Aug 21, 2010·Diabetes Care·Luigi BouchardDiane Brisson
Jan 27, 2011·PloS One·Fabienne BrenetJoseph M Scandura
Mar 24, 2011·Nature Reviews. Molecular Cell Biology·Mikiko C SiomiAlexei A Aravin
May 20, 2011·Epigenetics : Official Journal of the DNA Methylation Society·Juan SandovalManel Esteller
Oct 11, 2012·The Journal of Maternal-fetal & Neonatal Medicine : the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians·Nicholas M MordwinkinKathleen E Rodgers
Aug 27, 2013·Epigenetics : Official Journal of the DNA Methylation Society·Stephanie-May RuchatLuigi Bouchard
Sep 27, 2013·Pflügers Archiv : European journal of physiology·Minghua WuKuniaki Ishii
Oct 15, 2013·Biochemical and Biophysical Research Communications·Yosuke FunatoHiroaki Miki
Nov 22, 2014·Diabetes Care·Mark B LandonUNKNOWN Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network
Mar 31, 2015·Cell Reports·Elke F RooversRené F Ketting
May 13, 2015·Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association·C RongY Hu
Jun 14, 2016·Nature Communications·Martin GrothSteven E Jacobsen

❮ Previous
Next ❯

Citations

Dec 19, 2018·International Journal of Molecular Sciences·Paula HeppUdo Jeschke
Feb 25, 2020·The Journal of Maternal-fetal & Neonatal Medicine : the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians·Rao Gurugubelli KrishnaSreenivasulu Karli
Nov 20, 2018·PLoS Genetics·Fabien DelahayeFrancine Hughes
Jul 22, 2018·BioMed Research International·Larisa Montalvo-MartínezAlberto Camacho
Sep 12, 2018·International Journal of Molecular Sciences·Kathleen O'NeillSara E Pinney
Sep 6, 2019·Computational and Mathematical Methods in Medicine·Xue LiYanning Fang
Jul 21, 2020·The Journal of Clinical Endocrinology and Metabolism·Sara E PinneyPaul Zhipang Wang
Oct 13, 2020·Human Reproduction Update·Hannah E J Yong, Shiao-Yng Chan
Feb 8, 2021·Diabetes Research and Clinical Practice·Zain AwamlehRosanna Weksberg
Mar 21, 2021·Clinical Epigenetics·Chiara MocciaLorenzo Richiardi
May 29, 2021·Biology of Sex Differences·Amy M InksterWendy P Robinson
Jan 6, 2022·Medicinal Research Reviews·Suneesh KaimalaBright Starling Emerald

❮ Previous
Next ❯

Methods Mentioned

BETA
Chip
RNA-Seq
glycosylation

Software Mentioned

Illumina
Bioconductor
IPA
ImageJ
R platform
Mass Array Epityper
Genome Studio

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.

Cancer Epigenetics & Metabolism (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on the relationship between cell metabolism, epigenetics and tumor differentiation.