The role of folate in mitigating murine cardiac hypertrophy in offspring of diabetic dams

Abstract

Maternal diabetes is associated with short- and long-term cardiac disease. Prenatal folate is often recommended for diabetic pregnant women to reduce the incidence of cardiac and neural tube defects in their offspring. However, no such recommendation exists for the progeny of offspring of diabetic mothers despite the epidemiologic observation that there is a two-fold increase in cardiovascular disease. Contrary to previous reports, our lab has shown that left ventricular hypertrophy re-emerges in early adulthood. This study aimed to determine the role of folate supplementation in mitigating cardiac hypertrophy in the offspring of diabetic mice. Maternal hyperglycemia was induced in CD-1 females (n=10) with streptozotocin (150mg/kg). Control mice (n=10) were given an equal volume of saline. After hyperglycemia was confirmed ( >250mg/dL), both groups were mated with CD-1 males. After weaning, the offspring of diabetic (ODM) and control (OCM) were fed a non-supplemented versus supplemented folate diet for five weeks. Cardiac hypertrophy was assessed with echocardiograms at eight weeks and stratified by sex. We used t-test to compare the left ventricular internal diameter and left posterior wall thickness. P-values < 0.05 were significant. At eight weeks, compared to OCM, ODM had a smaller left ventricle internal diameter and increased posterior wall thickness consistent with myocardial hypertrophy. However, after receiving folate supplementation, only male ODM had a resolution of cardiac hypertrophy at eight weeks. For females ODM fed with folate supplementation, cardiac hypertrophy persisted. Folate did not mitigate cardiac hypertrophy overall. However, it did for male offspring of diabetic dams specifically. Folate supplementation may have a role in attenuating hypertrophy in male offspring of diabetic dams. Future studies will assess cardiac hypertrophy in the offspring of mothers with diabetes and determine if there is a role in post-natal folate supplementation.