Maternal undernutrition in late gestation increases IGF2 signalling molecules and collagen deposition in the right ventricle of the fetal sheep heart

Abstract

Exposure of the fetus to a range of environmental stressors, including maternal undernutrition, is associated with an increased risk of death from cardiovascular disease in adult life. This study aimed to determine the effect of maternal nutrient restriction in late gestation on the molecular mechanisms that regulate cardiac growth and development of the fetal heart. Maternal undernutrition resulted in a decrease in fetal glucose concentrations across late gestation, whilst fetal arterial PO2 remained unchanged between the control and late gestation undernutrition (LGUN) groups. There was evidence of an up-regulation of IGF2/IGF2R signalling through the CAMKII pathway in the fetal right ventricle in the LGUN group, suggesting an increase in hypertrophic signalling. LGUN also resulted in an increased mRNA expression of COL1A, TIMP1 and TIMP3 in the right ventricle of the fetal heart. In addition, there was an inverse relationship between fetal glucose concentrations and COL1A expression. The presence of interstitial fibrosis in the heart of the LGUN group was confirmed through the quantification of picrosirius red-stained sections of the right ventricle. We have therefore shown that maternal undernutrition in late gestation may drive the onset of myocardial remodelling in the fetal right ventricle and thus has negative implications for right ventricle function and cardiac health in later life.

Subcutaneous maternal resveratrol treatment increases uterine artery blood flow in the pregnant ewe and increases fetal but not cardiac growth

“…, ; Darby et al . ). Furthermore, in the chronically hypoxaemic late gestation fetal sheep heart, increased expression of IGF2 and IGF2R correlates with cardiomyocyte size, and this persists into postnatal life where LBW lambs have increased left ventricular mass (Wang et al .…”

Detecting metabolic differences in fetal and adult sheep adipose and skeletal muscle tissues

“…Bovine serum albumin (BSA; 2 mg/mL stock solution) was used to form a standard curve. Extracted protein samples (75 μg) were subject to sodium dodecyl surface (SDS) page and stained with Coomassie blue to determine equal protein loading[27][28][29][30].…”

And the beat goes on

“…For example, a severe 50% maternal nutrient restriction in late gestation increased myocardial fibrosis and altered the phosphorylation state of key contractile proteins in the fetal sheep right ventricle (Darby et al . ). CMRI has recently been employed to study the fetal heart (Duan et al .…”