ELABELA alleviates syncytiotrophoblast hypoxia/reoxygenation injury and preeclampsia-like symptoms in mice by reducing apoptosis

Placenta. 2021 Mar:106:30-39. doi: 10.1016/j.placenta.2021.02.002. Epub 2021 Feb 11.

Abstract

Introduction: Preeclampsia (PE) is associated with increased syncytiotrophoblast apoptosis. ELABELA (ELA) is a circulating hormone secreted by the placenta. Here, we investigated the involvement of ELA in the pathogenesis of PE.

Methods: We measured ELA expression in the placental villi of patients with severe PE and healthy controls. A cellular model of hypoxia and reoxygenation was used to simulate PE hypoxia, and changes in the proliferation and apoptosis of trophoblasts in response to different ELA concentrations were measured. In addition, we used NG-nitro-l-arginine methyl ester (l-NAME) to generate a mouse model of pregnancy-induced hypertension and explore whether ELA can improve the symptoms of PE.

Results: ELA expression was decreased in severe PE. ELA promoted the proliferation of BeWo cells and improved the decreased cell proliferation rate after hypoxia/reoxygenation injury. ELA reversed the phenotypes of l-NAME-induced PE mice and regulated the expression of mouse placental apoptosis factors.

Discussion: ELA reduced apoptosis in BeWo cells and improved PE-like symptoms in mice, suggesting its value as a potential novel treatment for PE.

Keywords: Apoptosis; ELABELA; Placenta; Preeclampsia; Syncytiotrophoblast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Cell Line
  • Disease Models, Animal
  • Female
  • Humans
  • Hypoxia / drug therapy*
  • Hypoxia / metabolism
  • Mice
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Peptide Hormones / metabolism
  • Peptide Hormones / pharmacology*
  • Peptide Hormones / therapeutic use
  • Placenta / drug effects*
  • Placenta / metabolism
  • Pre-Eclampsia / drug therapy*
  • Pre-Eclampsia / metabolism
  • Pregnancy
  • Trophoblasts / drug effects*
  • Trophoblasts / metabolism

Substances

  • APELA protein, human
  • Peptide Hormones
  • NG-Nitroarginine Methyl Ester