*3.4. Oxidative Stress and Hypoxia*

During the first trimester of pregnancy, the placenta develops in an environment with a relatively low oxygen supply of only 20mmHg at 8 weeks, rising to >50 mmHg at 12 weeks, as the maternal uterine artery blood flow increases [18]. Hypoxia-inducible nuclear factors HIF1α and HIF2α are master regulators of the hypoxia response in tissues, and are also expressed in the early-pregnancy placenta [19,20]. Levels of HIF1α are significantly lower in placentas gathered from pregnancies with high uterine artery resistance despite the expectation that placental hypoxia or oxidative stress would be associated with higher levels of HIF1α [8]. The latter tissues expressed an altered balance of antioxidant enzyme activity (lower glutathione peroxidase and higher superoxide dismutase activity) when compared with normal placental tissue. These findings all sugges<sup>t</sup> that hypoxia and oxidative stress appear to be a physiological state in early pregnancy.
