Insights from animal models: Dissecting the independent roles of oxygen and nutrients in the fetal origins of cardiovascular disease.

Depending on the pregnancy complication, substrate delivery to a developing fetus can be reduced, changing the course of fetal growth below the genetically determined in utero growth potential, resulting in fetal growth restriction (FGR). FGR is linked to an increased risk of developing cardiovascular disease (CVD) in later life. When caused by placental insufficiency, FGR is characterized by fetal hypoxaemia and hypoglycaemia due to reduced substrate supply to the fetus. However, other common pregnancy complications exist, where fetal hypoxaemia or hypoglycaemia may or may not occur. It is therefore necessary to understand the independent and synergistic contributions of hypoxaemia and hypoglycaemia to the fetal origins of CVD. In doing so, this knowledge will aid in the development of intervention strategies. The aim of this review is to provide mechanistic insights by comparing findings across different paradigms of developmental programming using animal models of FGR, with consideration of the timing, duration, and severity of the insult, and the ventricles and fetal sex studied.