Effect of preeclampsia on placental function: Influence of sexual dimorphism, microRNA's and mitochondria

Leslie Myatt, Sribalasubashini Muralimanoharan, Alina Maloyan

Research output: Chapter in Book/Report/Conference proceedingChapter

28 Scopus citations

Abstract

In pregnancy fetal growth and development occur in a sexually dimorphic manner. Male and female fetuses respond differently to the intrauterine environment with males disproportionately suffering from perinatal morbidity and mortality. We have demonstrated placental dysfunction and sexually dimorphic responses in pregnancies complicated by severe preeclampsia. Production of cytokines and apoptosis in the male placenta is heightened relative to that of the female placenta. We also find increased expression and stabilization and a sexual dimorphism in expression of the transcription factor HIF-1α, but a defect in binding to the hypoxia response element with corresponding reduced expression of HIF-1α target genes including VEGF and Glut-1. HIF-1α is involved in crosstalk with the redox sensitive transcription factor NFκB in regulation by cytokines, reactive oxygen species and expression of inflammatory genes. We find increased placental expression and DNA binding of NFκB and a sexually dimorphic response suggesting a role for NFκB in placental dysfunction with preeclampsia. Placental mitochondrial complex III activity and complex I and IV expression are reduced and alterations in mitochondrial morphology are found in preeclampsia and are linked to the hypoxamir miR-210. We propose that with severe PE placental HIF-1α is stabilized by excessive ROS, inflammation and relative hypoxia. This increases the expression of miR-210 in the placenta causing repression of mitochondria-associated target genes, potentially leading to mitochondrial and placental dysfunction. This placental dysfunction may lead to a fetal programming effect that results in disease in later life.

Original languageEnglish (US)
Title of host publicationAdvances in Fetal and Neonatal Physiology
Subtitle of host publicationProceedings of the Center for Perinatal Biology 40th Anniversary Symposium
PublisherSpringer New York LLC
Pages133-146
Number of pages14
ISBN (Print)9781493910304
DOIs
StatePublished - 2014

Publication series

NameAdvances in Experimental Medicine and Biology
Volume814
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

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Keywords

  • Fetus
  • Inflammation
  • Mitochondria
  • Obesity
  • Oxidative stress
  • Placenta
  • Preeclampsia
  • Pregnancy
  • Sexual dimorphism

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Myatt, L., Muralimanoharan, S., & Maloyan, A. (2014). Effect of preeclampsia on placental function: Influence of sexual dimorphism, microRNA's and mitochondria. In Advances in Fetal and Neonatal Physiology: Proceedings of the Center for Perinatal Biology 40th Anniversary Symposium (pp. 133-146). (Advances in Experimental Medicine and Biology; Vol. 814). Springer New York LLC. https://doi.org/10.1007/978-1-4939-1031-1_12