Impaired mitochondrial function in human placenta with increased maternal adiposity

James Mele, Sribalasubashini Muralimanoharan, Alina Maloyan, Leslie Myatt

Research output: Contribution to journalArticlepeer-review

120 Scopus citations

Abstract

The placenta plays a key role in regulation of fetal growth and development and in mediating in utero developmental programming. Obesity, which is associated with chronic inflammation and mitochondrial dysfunction in many tissues, exerts a programming effect in pregnancy. We determined the effect of increasing maternal adiposity and of fetal sex on placental ATP generation, mitochondrial biogenesis, expression of electron transport chain subunits, and mitochondrial function in isolated trophoblasts. Placental tissue was collected from women with prepregnancy BMI ranging from 18.5 to 45 following C-section at term with no labor. Increasing maternal adiposity was associated with excessive production of reactive oxygen species and a significant reduction in placental ATP levels in placentae with male and female fetuses. To explore the potential mechanism of placental mitochondrial dysfunction, levels of transcription factors regulating the expression of genes involved in electron transport and mitochondrial biogenesis were measured. Our in vitro studies showed significant reduction in mitochondrial respiration in cultured primary trophoblasts with increasing maternal obesity along with an abnormal metabolic flexibility of these cells. This reduction in placental mitochondrial respiration in pregnancies complicated by maternal obesity could compromise placental function and potentially underlie the increased susceptibility of these pregnancies to fetal demise in late gestation and to developmental programming.

Original languageEnglish (US)
Pages (from-to)E419-E425
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume307
Issue number5
DOIs
StatePublished - Sep 1 2014

Keywords

  • Mitochondria
  • Obesity
  • Placenta

ASJC Scopus subject areas

  • General Medicine

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