Maternal Early Overfeeding Negatively Impacts Cardiac Progenitor Cell Differentiation and Cardiomyocyte Maturation in the Neonatal Offspring

Abstract

Introduction: Maternal obesity has been positively correlated with an increased cardiometabolic risk in the offspring throughout life, implying intergenerational transmission. However, little is known about the early life cardiac cell modifications that imply the onset of heart diseases later in life. This study analyzed cardiac progenitor cells and cardiomyocyte differentiation on day of birth in the offspring born to obese dams. Methods: The litter size reduction model was used to induce obesity in female Swiss mice. Both maternal groups, the Small Litter Dams (SLD-F1), which were overfed during lactation, and the Normal Litter Dams (NLD-F1), control group, were mated to healthy male mice. Their first generation offspring (SLD-F2 and NLD-F2, n=6 by group) were euthanized on birth. Results: Mothers from SLD had increased body mass, Lee Index, fat deposits, hyperglycemia, and glucose intolerance, confirming the obese phenotype. The offspring born from SLD-F1 had also increased body mass, Lee Index, and fasting hyperglycemia. The heart of SLD-F2 showed decreased cardiac mass/body mass ratio, increased cardiac collagen deposits, and a greater number of undifferentiated cardiac c-kit+ and Sca-1+ progenitor cells, and increased NKX2.5+ cardiomyoblasts compared to control. In addition, SLD-F2 demonstrated immature cardiomyocytes.Conclusions: Obese dams negatively impact its offspring, leading to altered biometric and metabolic parameters, along with an immature heart already at birth, with extracellular matrix adverse remodeling, delayed cardiac progenitor cells differentiation and restrained cardiomyocyte maturation, which can be related with the development of cardiometabolic disease in the adulthood.