The developmental origin of health and disease (DOHaD) hypothesis refers to the adverse effects of suboptimal developmental environments during embryonic and early fetal stages on the long-term health of offspring. Intrauterine metabolic perturbations can profoundly impact organogenesis in offspring, particularly affecting cardiac development and giving rise to potential structural and functional abnormalities. In this discussion, we contemplate the existing understanding regarding the impact of maternal metabolic disorders, such as obesity, diabetes, or undernutrition, on the developmental and functional aspects of the offspring's heart. This influence has the potential to contribute to the susceptibility of offspring to cardiovascular health issues. Alteration in the nutritional milieu can influence mitochondrial function in the developing hearts of offspring, while also serving as signaling molecules that directly modulate gene expression. Moreover, metabolic disorders can exert influence on cardiac development-related genes epigenetically through DNA methylation, levels of histone modifications, microRNA expression, and other factors. However, the comprehensive understanding of the mechanistic underpinnings of these phenomena remains incomplete. Further investigations in this domain hold profound clinical significance, as they can contribute to the enhancement of public health and the prevention of cardiovascular diseases.
Keywords: DOHaD; cardiovascular diseases; congenital heart defects; maternal diabetes; maternal obesity; metabolism.