Shared developmental pathways of the placenta and fetal heart.

Congenital heart defects (CHD) remain the most common class of birth defect worldwide, affecting 1 in every 110 live births. A host of clinical and morphological indicators of placental dysfunction are observed in pregnancies complicated by fetal CHD and, with the recent emergence of single-cell sequencing capabilities, the molecular and physiological associations between the embryonic heart and developing placenta are increasingly evident. In CHD pregnancies, a hostile intrauterine environment may negatively influence and alter fetal development. Placental maldevelopment and dysfunction creates this hostile in-utero environment and may manifest in the development of various subtypes of CHD, with downstream perfusion and flow-related alterations leading to yet further disruption in placental structure and function. The adverse in-utero environment of CHD-complicated pregnancies is well studied, however the specific etiological role that the placenta plays in CHD development remains unclear. Many mouse and rat models have been used to characterize the relationship between CHD and placental dysfunction, but these paradigms present substantial limitations in the assessment of both the heart and placenta. Improvements in non-invasive placental assessment can mitigate these limitations and drive human-specific investigation in relation to fetal and placental development. Here, we review the clinical, structural, and molecular relationships between CHD and placental dysfunction, the CHD subtype-dependence of these changes, and the future of Placenta-Heart axis modeling and investigation.