Anton 2019 Front Physiol

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Anton L, DeVine A, Polyak E, Olarerin-George A, Brown AG, Falk MJ, Elovitz MA (2019) HIF-1α stabilization increases miR-210 eliciting first trimester extravillous trophoblast mitochondrial dysfunction. Front Physiol 10:699.

» PMID: 31263422 Open Access

Anton L, DeVine A, Polyak E, Olarerin-George A, Brown AG, Falk MJ, Elovitz MA (2019) Front Physiol

Abstract: Preeclampsia is associated with first trimester placental dysfunction. miR-210, a small non-coding RNA, is increased in the preeclamptic placenta. The effects of elevated miR-210 on placental function remain unclear. The objectives of this study were to identify targets of miR-210 in first trimester primary extravillous trophoblasts (EVTs) and to investigate functional pathways altered by elevated placental miR-210 during early pregnancy. EVTs isolated from first trimester placentas were exposed to cobalt chloride (CoCl2), a HIF-1α stabilizer and hypoxia mimetic, and miR-210 expression by qPCR, HIF1α protein levels by western blot and cell invasion were assessed. A custom TruSeq RNA array, including all known/predicted miR-210 targets, was run using miR-210 and miR-negative control transfected EVTs. Mitochondrial function was assessed by high resolution respirometry in transfected EVTs. EVTs exposed to CoCl2 showed a dose and time-dependent increase in miR-210 and HIF1α and reductions in cell invasion. The TruSeq array identified 49 altered genes in miR-210 transfected EVTs with 27 genes repressed and 22 enhanced. Three of the top six significantly repressed genes, NDUFA4, SDHD, and ISCU, are associated with mitochondrial function. miR-210 transfected EVTs had decreased maximal, complex II and complex I+II mitochondrial respiration. This study suggests that miR-210 alters first trimester trophoblast function. miR-210 overexpression alters EVT mitochondrial function in early pregnancy. Mitochondrial dysfunction may lead to increased reactive oxygen species, trophoblast cell damage and likely contributes to the pathogenesis of preeclampsia.

Keywords: ISCU, NDUFA4, SDHD, Extravillous trophoblast, miR-210, miRNA, Mitochondrial respiration, Preeclampsia Bioblast editor: Plangger M O2k-Network Lab: US PA Philadelphia Falk MJ

Labels: MiParea: Respiration, nDNA;cell genetics  Pathology: Other 

Organism: Human  Tissue;cell: Genital  Preparation: Permeabilized cells 

Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, NS, ROX  HRR: Oxygraph-2k