PMID: 32537569Jan 1, 2019Paper

Intrauterine Programming of Diabetes Induced Cardiac Embryopathy

Diabetes & Obesity International Journal
Rolanda ListerBin Zhou

Abstract

Maternal hyperglycemia is a well-recognized risk factor for fetal congenital heart disease. However, the underlying cellular and molecular mechanisms are not well characterized. We hypothesize that maternal hyperglycemia leading to congenital heart are linked to abnormal DNA methylation and mRNA expression at cardiac specific loci. Hyperglycemia was induced in normal 8-week old CD-1 female mice with a one-time intraperitoneal injection of 150 mg/kg of streptozotocin (STZ) 2 weeks prior to mating. Histological analysis of fetal cardiac morphology was evaluated for malformations on embryonic day (E) 16.5 of control pups and pups exposed to maternal hyperglycemia. We used a massively-parallel sequencing-based methylation sensitive restriction based assay to examine genome-wide cytosine methylation levels at >1.65 million loci in neonatal hearts on post-natal (P) day 0. Functional validation was performed with real time quantitative polymerase chain reaction (RT-qPCR). Cardiac structural defects occurred in 28% of the pups (n=12/45) of hyperglycemic dams versus 7% (n=4/61) of controls. Notable phenotypes were hypoplastic left or right ventricle, double outlet right ventricle, ventricular septal defect, and left ventricular outflow ...Continue Reading

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