Gestational protein restriction: Study of the probable effects on cardiac muscle structure and function in adult rats

Abstract

Intrauterine growth restriction (IUGR) has been linked to heart disease in adulthood. This study aimed to examine the effect of gestational protein restriction during fetal and early postnatal life on the cardiac muscle structure and function in adult offspring. Pregnant female rats were randomly divided into two dietary groups: normal-protein diet (NP) and low-protein diet (LP). Fifteen male offspring from each group were included in the study. Offspring body weights were recorded at birth and monthly from weaning until 24 weeks of age while systolic blood pressure was measured weekly. At the end of the experiment, hearts were weighed and processed for light and electron microscopy and immunohistochemical study. Immunohistochemical staining for localization of inducible nitric oxide synthase (iNOS) and connexin 43 proteins was performed. The gestational protein restriction induced deleterious effects on adult offspring including decreased birth weight, heart weight, and heart rate, and increased systolic blood pressure. Histologically, the number of cardiomyocytes decreased and cardiac fibrosis increased. Signs of degeneration at both structural and ultra-structural levels of cardiomyocytes were also seen. The iNOS was up regulated in LP offspring which was a promoter for apoptosis, while connexin 43 was down regulated which would affect heart conductivity and contractility. Our results demonstrate that adult offspring body weight and cardiac muscle structure and function can be programmed by maternal gestational nutrition. These adverse outcomes suggest the criticality of dietary behavior during pregnancy on long-term offspring cardiac health.