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Changes in oxygen levels characterize normal and pathological human placentation. For example, relatively low Po ₂values are present around the blastocyst during implantation and in the placenta of the first trimester of pregnancy, a time of maximal trophoblast invasion. Our studies have revealed that low oxygen levels stimulate the in vitro invasiveness of cultured first trimester trophoblasts. This increased invasive ability is linked to elevated expression of some components of the plasminogen activator system and requires the participation of a putative haem protein. As gestation proceeds beyond the first trimester, and the extent of trophoblast invasion decreases, placental oxygen levels rise with a corresponding increase in blood flow. However, during certain pathological conditions, such as pre-eclampsia/intrauterine growth restriction, impaired remodelling of the uterine spiral arterioles leads to vessels with …