Reprogramming of the developing heart by Hif1a-deficient sympathetic system and maternal diabetes exposure.

Introduction: Maternal diabetes is a recognized risk factor for both short-term and long-term complications in offspring. Beyond the direct teratogenicity of maternal diabetes, the intrauterine environment can influence the offspring's cardiovascular health. Abnormalities in the cardiac sympathetic system are implicated in conditions such as sudden infant death syndrome, cardiac arrhythmic death, heart failure, and certain congenital heart defects in children from diabetic pregnancies. However, the mechanisms by which maternal diabetes affects the development of the cardiac sympathetic system and, consequently, heightens health risks and predisposes to cardiovascular disease remain poorly understood. Methods and results: In the mouse model, we performed a comprehensive analysis of the combined impact of a Discussion: Our data demonstrate that a failure to adequately activate the HIF-1α regulatory pathway, particularly in the context of maternal diabetes, may contribute to abnormalities in the cardiac sympathetic system. In conclusion, our findings indicate that the interplay between deficiencies in the cardiac sympathetic system and subtle structural alternations in the vasculature, microvasculature, and myocardium during heart development not only increases the risk of cardiovascular disease but also diminishes the adaptability to the stress associated with the transition to extrauterine life, thus increasing the risk of neonatal death.