Does the Biological Response to Fetal Hypoxia Involve Angiogenesis, Placental Enlargement and Preeclampsia?

From an evolutionary point of view, an overriding biological priority is to ensure offspring survival. Oxygen is essential for the growing fetus, and during pregnancy the fetus has an increasing demand for oxygen. If the oxygen supply to the fetus is threatened, it is likely that compensatory mechanisms are activated. Impaired development of the placenta in early pregnancy is assumed to be the main cause of fetoplacental hypoxia and preeclampsia. However, it is also plausible that medical conditions in the mother could lead to sub-optimal supply to the feto-placental unit. Feto-placental hypoxia may in such mothers develop in the last part of pregnancy when the oxygen demand is highest. We propose that in pregnancies with sub-optimal availability of oxygen in maternal blood, placental dysfunction may not be the primary cause of feto-placental hypoxia and preeclampsia. On the contrary, in these pregnancies, increased placental growth may be important as a compensatory mechanism to improve oxygen uptake from the maternal circulation. On the basis of results from population studies, we hypothesise that both impaired placental development in early pregnancy and insufficient oxygen supply from the maternal circulation later in pregnancy, may cause feto-placental hypoxia and preeclampsia (Figure 1). In the following, we will present arguments for such hypothesis.