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

119 Citations (Scopus)

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 2012

Fingerprint

Pre-Eclampsia
Placenta
Respiration
Trophoblasts
MicroRNAs
sulofenur
Pregnancy
Smegmamorpha
Fetal Mortality
Small Untranslated RNA
Messenger RNA
Electron Transport Complex III
RNA Stability
Oxygen Consumption
Transfection
Mitochondria
Up-Regulation
Down-Regulation
Mothers
Morbidity

Keywords

  • miR-210
  • Mitochondria
  • Placenta
  • Preeclampsia

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Reproductive Medicine
  • Developmental Biology

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

MIR-210 modulates mitochondrial respiration in placenta with preeclampsia. / Muralimanoharan, S.; Maloyan, A.; Mele, J.; Guo, C.; Myatt, L. G.; Myatt, L.

In: Placenta, Vol. 33, No. 10, 10.2012, p. 816-823.

Research output: Contribution to journalArticle

Muralimanoharan, S, Maloyan, A, Mele, J, Guo, C, Myatt, LG & Myatt, L 2012, 'MIR-210 modulates mitochondrial respiration in placenta with preeclampsia', Placenta, vol. 33, no. 10, pp. 816-823. https://doi.org/10.1016/j.placenta.2012.07.002
Muralimanoharan S, Maloyan A, Mele J, Guo C, Myatt LG, Myatt L. MIR-210 modulates mitochondrial respiration in placenta with preeclampsia. Placenta. 2012 Oct;33(10):816-823. https://doi.org/10.1016/j.placenta.2012.07.002
Muralimanoharan, S. ; Maloyan, A. ; Mele, J. ; Guo, C. ; Myatt, L. G. ; Myatt, L. / MIR-210 modulates mitochondrial respiration in placenta with preeclampsia. In: Placenta. 2012 ; Vol. 33, No. 10. pp. 816-823.
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