Zohar Bromberg, Rinat Abramovitch, Prof. Yehuda Ginosar, MD.

The Goldyne Savad Institute of Gene Therapy, Hadassah Hospital, Jerusalem. 

Introduction: Impaired uteroplacental blood flow and chronic fetal asphyxia is implicated in the “great obstetrical syndromes” of preterm delivery, preeclampsia and fetal growth restriction. Without intervention, chronic fetal asphyxia may progress to hypoxic ischemic neonatal encephalopathy and increases the risk of acute intrapartum fetal asphyxia. As no interventions are currently available to improve placental blood flow, there is often no alternative to interventional delivery in these cases.

 

Material and methods: We developed a mouse model of chronic hypoxia (FiO2 12%), imposed by placing mice in a large hypoxic animal cabinet. The chamber is fitted with independent O2 and CO2 sensors and controllers and a filtration system with humidity control. The mice are placed inside the hypoxic cabinet between: E10-E18. Functional MRI was used in order to detect the oxygen consumption and blood flows. Confocal images were used in order to trace Hypoxia Inducible Factors (HIFs) patterns within the hypoxic placentas.

Results: fMRI demonstrated a reduction of placental and fetal perfusion following hypoxia.  For the first time, we found that placental blood vessels were positively stained to HIFs. Further, chronic hypoxia elevates cytoplasmic and peri-nuclear HIF-1α co-localized with PCNA (proliferation marker) in Trophoblasts Giant Cells (TGCs) located around the placental spiral artery.

Conclusion: HIFs may play essential, important and distinct roles within the placenta, specifically for each cell type, during hypoxic conditions and normal pregnancy. HIF-1α could have an effect on spiral artery remodeling and may regulate placental blood vessels.