Sexual dimorphism in MIR-210 expression and mitochondrial dysfunction in the placenta with maternal obesity

S. Muralimanoharan, C. Guo, Leslie Myatt, Alina Maloyan

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Background:Maternal obesity is a major problem in obstetrics, and the placenta is involved in obesity-related complications via its roles at the maternal-fetal interface. We have recently shown a causative role for micro(mi)RNA-210, a so called 'hypoxamir' regulated by HIF-1, in mitochondrial dysfunction in placentas from women with preeclampsia. We also reported mitochondrial dysfunction in placentas with maternal obesity. Here we hypothesized that expression of miR-210 is dysregulated in the placentas with obesity.Methods:Placentas from uncomplicated pregnancies were collected at term from healthy weight or control (CTRL, pre-pregnancy body mass index (BMI)30) women following C-section with no labor. Expression of miRNA-210 and its target genes was measured by reverse transcription-PCR and Western Blot, respectively. Mitochondrial respiration was assessed by Seahorse Analyzer in syncytiotrophoblast (ST) 72 h after cytotrophoblast isolation.Results:Expression of miR-210 was significantly increased in placentas of OB and OW women with female but not male fetuses compared with CTRL placentas of females. However, expression of HIF-1 in these placentas remained unchanged. Levels of tumor-necrosis factor-alpha (TNF) were increased in OW and OB placentas of females but not males, and in silico analysis suggested that activation of miR-210 expression in these placentas might be activated by NFκB1 (p50) signaling. Indeed, chromatin Immunoprecipitation assay showed that NFkB1 binds to placental miR-210 promoter in a fetal sex-dependent manner. Female but not male STs treated with TNF showed overexpression of miR-210, reduction of mitochondrial target genes and decreased mitochondrial respiration. Pre-treatment of these STs with small interfering RNA to NFkB1 or antagomiR-210 prevented the TNF-mediated inhibition of mitochondrial respiration.Conclusions:Our data suggest that the inflammatory intrauterine environment associated with maternal obesity induces an NFκB1-mediated increase in miR-210 in a fetal sex-dependent manner, leading to inhibition of mitochondrial respiration and placental dysfunction in the placentas of female fetuses.

Original languageEnglish (US)
Pages (from-to)1274-1281
Number of pages8
JournalInternational Journal of Obesity
Volume39
Issue number8
DOIs
StatePublished - Aug 6 2015
Externally publishedYes

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Sex Characteristics
Placenta
Obesity
Mothers
Respiration
Tumor Necrosis Factor-alpha
Trophoblasts
MicroRNAs
Fetus
Smegmamorpha
Activation Analysis
Pregnancy
Mitochondrial Genes
Chromatin Immunoprecipitation
Pre-Eclampsia
Computer Simulation
Small Interfering RNA
Reverse Transcription
Obstetrics
Body Mass Index

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics
  • Endocrinology, Diabetes and Metabolism

Cite this

Sexual dimorphism in MIR-210 expression and mitochondrial dysfunction in the placenta with maternal obesity. / Muralimanoharan, S.; Guo, C.; Myatt, Leslie; Maloyan, Alina.

In: International Journal of Obesity, Vol. 39, No. 8, 06.08.2015, p. 1274-1281.

Research output: Contribution to journalArticle

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