MIR-210 modulates mitochondrial respiration in placenta with preeclampsia

S. Muralimanoharan, A. Maloyan, J. Mele, C. Guo, L. G. Myatt, L. Myatt

Research output: Contribution to journalArticle

130 Scopus citations

Abstract

Preeclampsia (PE) affects 5-8% of all pregnancies and is associated with significant maternal and fetal morbidity and mortality. Placental mitochondrial dysfunction has been reported in PE. MicroRNAs (miRNA) are small non-coding RNAs that regulate gene expression through mRNA degradation and translational repression. MiR-210 has been previously shown to be upregulated in placentas from pregnancies complicated by PE. We hypothesized that placental mitochondrial dysfunction during PE can be mediated by miR-210. Placentas were collected at term from normotensive pregnancies (CTRL) and those complicated by severe PE (n = 6 each) following c-section (no labor). Villous tissue from PE showed significantly increased levels of HIF-1α compared to CTRL with no change in corresponding mRNA expression but with reduced DNA-binding activity. Mitochondrial complex III was significantly decreased in PE along with significantly reduced protein expression in complex I and IV during PE. Among the four miRNAs tested, miR-210 showed significant up regulation in PE and significant downregulation of its target, ISCU mRNA. To understand the role of miR-210 in PE, loss- and gain-of-function studies were performed using primary trophoblasts. Trophoblasts were transfected with miR-210 inhibitor or pre-miR-210 and mitochondrial function was measured using Seahorse Extracellular Flux Analyzer. Cells transfected with pre-miR-210 showed significant reduction in oxygen consumption. In contrast, transfection of trophoblast with AntagomiR-210 was sufficient to prevent the DFO-mediated respiratory deficiency. These data collectively suggest that miR-210 overexpression during PE could be responsible for placental mitochondria dysfunction.

Original languageEnglish (US)
Pages (from-to)816-823
Number of pages8
JournalPlacenta
Volume33
Issue number10
DOIs
StatePublished - Oct 1 2012

Keywords

  • Mitochondria
  • Placenta
  • Preeclampsia
  • miR-210

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology
  • Developmental Biology

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  • Cite this

    Muralimanoharan, S., Maloyan, A., Mele, J., Guo, C., Myatt, L. G., & Myatt, L. (2012). MIR-210 modulates mitochondrial respiration in placenta with preeclampsia. Placenta, 33(10), 816-823. https://doi.org/10.1016/j.placenta.2012.07.002