The regulation of trophoblast differentiation by oxygen in the first trimester of pregnancy

In the first trimester of human pregnancy villous cytotrophoblasts are able to differentiate to form either the overlying syncytiotrophoblast layer or, in anchoring villi, extravillous trophoblasts which grow out from the villi and invade into the maternal decidua, acting to both physically attach the placenta to the decidua, and modify the maternal spiral arteries to sustain pregnancy. During the first 10-12 weeks of gestation, extravillous trophoblast plugs block the spiral arteries and prevent maternal blood flow entering the intervillous space, thereby creating an environment of physiological hypoxia in which placental and fetal development occur. As extravillous trophoblasts migrate away from the villus they differentiate from a proliferative to an invasive phenotype. The hypoxic environment of the first trimester is believed to play an important role in the regulation of trophoblast differentiation. However, there is currently a large body of conflicting experimental evidence concerning this topic. This review examines the experimental evidence to date on the role of oxygen in trophoblast differentiation.