Placental Adaptation to Hypoxia-Induced FGR

Proper oxygenation of the placenta and the fetus are essential for normal pregnancy development. Accordingly, maternal gestational hypoxia constitutes a factor risk for fetal growth restriction (FGR) incidence. However, the molecular mechanism underlying this detrimental complication remains unclear. We explored the adaptation to hypoxic environment during pregnancy to support O₂ (oxygen) transport in pregnant mice and fetal survival using non-invasive in-vivo MRI technique.

In this study, pregnant mice were subjected to either normoxic (21% O₂) or hypoxic (12.5% O₂) conditions during gestation and imaged in a 15.2T MRI. To further investigate the mechanism of oxygen transfer from the mother to the fetus, we looked at the placental expression of BPGM, the enzyme responsible for the synthesis of 2, 3 BPG, an allosteric modulator of hemoglobin-oxygen affinity. We also observed structural changes in the placentae following maternal hypoxia.

Our results demonstrate a higher incidence of FGR in the hypoxic chamber group. The MR experiments showed that maternal hypoxia altered maternal, fetal and placental hemoglobin-oxygen affinity. We demonstrate a novel and unique polar expression of the BPGM enzyme in the spiral artery trophoblast cells (SpA TC) that come in direct contact with maternal blood, which presumably facilitates O₂ transfer from the mother to the fetus. We also demonstrate structural changes in the hypoxic placentae as well as enlarged spiral arteries and elevation in erythrocyte levels. These results enabled us to explore the mechanisms of adaptation to oxygen deprivation, as well as to determine its effect on embryonic and placental development.