The Human Placenta in Diabetes and Obesity: Friend or Foe? The 2017 Norbert Freinkel Award Lecture.

The placenta plays a key role in sustaining fetal growth and development. Due to its position between mother and fetus, it is exposed to changes in the intrauterine environment in both circulations. The relative influence of changes in those circulations depends on the period of gestation. Early in pregnancy, maternal influences prevail and may affect the complex biological processes characteristic for this pregnancy period, such as placentation, early cell differentiation, and spiral artery remodeling. It is still unclear whether the placenta early in pregnancy is a friend or foe for the fetus. Later in pregnancy, when the fetal circulation is gradually establishing, fetal signals gain importance in regulating placental structure and function. Many of the placental alterations seen at term of pregnancy are the result of fetoplacental interactions often driven by fetal signals associated with maternal diabetes or obesity. These alterations, such as hypervascularization or enhanced cholesterol removal from placental endothelial cells, can be regarded as adaptations to maintain homeostasis at the fetoplacental interface and, thus, to protect the fetus. However, extreme conditions such as poorly controlled diabetes or pronounced obesity may exceed placental homeostatic capacity, with potentially adverse consequences for the fetus. Thus, in late pregnancy, the placenta acts mostly as a friend as long as the environmental perturbations do not exceed placental capacity for mounting adaptive responses.