HIF1-α induces mitochondrial fission in trophoblastic cells during early pregnancy and in preeclampsia.

The placenta undergoes a major oxygen transition between 7 and 9 gestation weeks (GW) and 12-14 GW. Inadequate adaptation to these environmental changes leads to oxidative stress and the release of syncytial knots, a hallmark of preeclampsia (PE). As mitochondria play a central role in redox regulation, we investigated mitochondrial network dynamics and the role of hypoxia-inducible factor 1-alpha (HIF1-α) in trophoblasts during early pregnancy and in PE. HIF1-α is stabilized in placenta before 9 GW, associated with mitochondrial hypertubulation and increased mitofusin (MFN) 1 expression. Experimental stabilization of HIF1-α using cobalt chloride induces mitochondrial fission through downregulation of MFN1 and MFN2, and upregulation of dynamin-related protein 1 (DRP1). In pre-eclamptic placentas, significantly elevated mitochondrial fission 1 protein (FIS1) levels suggest enhanced mitochondrial fission, supporting FIS1 as a potential biomarker of PE-associated placental alterations.