Offspring Sex Impacts DNA Methylation and Gene Expression in Placentae from Women with Diabetes during Pregnancy

Exposure to diabetes in utero is known to increase the offspring's likelihood of developing metabolic disease in adulthood, but the mechanisms involved are unknown. It has been proposed that early exposure to hyperglycemia and elevated insulin levels may lead to malprogramming of the fetus leading to the subsequent development of diabetes and obesity. Epigenetic modifications of the genome including DNA methylation, provide a plausible mechanism that allows for permanent propagation of gene activity states from one generation of cells to the next.

The placenta, a fetal tissue easily accessible for study, is a complex organ that is essential in regulating fetal growth. The changes in placental nutrient transport associated with diabetes during pregnancy (DDP) have significant effects on the developing fetus, indicating that the placenta plays a critical role in fetal programming. The aim of our study was to investigate whether exposure to DDP alters genome-wide DNA methylation in the placenta obtained from term pregnancies resulting in differentially methylated loci of metabolically relevant genes and downstream changes in RNA and protein expression.

• Study Design:
  • Case-Control
• Study Type:
  • Nested Case-Control
• Total number of consented subjects: 34
• Subject Sample Telemetry Report (SSTR)

• BioProject
• BioSample
• MeSH
• Gene

Native American and Hispanic women experiencing a pregnancy complicated by diabetes (DDP, n=17) diagnosed by American Diabetes Association criteria, were selected from a larger cohort of maternal/offspring dyads with exposure to DDP. Seventeen women without a history of diabetes during pregnancy were selected as control participants from the same larger cohort of maternal/offspring dyads. Exclusion criteria included preterm delivery, congenital birth defects, birth asphyxia, congenital infection, offspring metabolic disease, or maternal complications (e.g. preeclampsia).

• Primary Phenotype: Diabetes, Gestational

• CYBA
• GSTM1
• GSTM5
• KCNE1
• NXN
• PIWIL3

• Principal Investigator
  • Steven Chernausek, MD. Department of Pediatrics, CMRI Metabolic Research Program, and Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
• Funding Sources
  • R01-DK089034-03. National Institutes of Health, Bethesda, MD, USA.
  • K08 DK0903-02. National Institutes of Health, Bethesda, MD, USA.
  • 1-10-CT-09. American Diabetes Association, Arlington, VA, USA.