Anton 2019 Front Physiol
| Anton L, DeVine A, Polyak E, Olarerin-George A, Brown AG, Falk MJ, Elovitz MA (2019) HIF-1ฮฑ stabilization increases miR-210 eliciting first trimester extravillous trophoblast mitochondrial dysfunction. Front Physiol 10:699. |
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-1ฮฑ stabilizer and hypoxia mimetic, and miR-210 expression by qPCR, HIF1ฮฑ 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 HIF1ฮฑ 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. โข Keywords: ISCU, NDUFA4, SDHD, Extravillous trophoblast, miR-210, miRNA, Mitochondrial respiration, Preeclampsia โข Bioblast editor: Plangger M โข 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
2020-05
