Galectin-7 impairs placentation and causes preeclampsia features in mice

Ellen Menkhorst, Wei Zhou, Leilani L. Santos, Sarah Delforce, Teresa So, Kate Rainczuk, Hannah Loke, Argyro Syngelaki, Swati Varshney, Nicholas Williamson, Kirsty Pringle, Morag J. Young, Kypros H. Nicolaides, Yves St-Pierre, Eva Dimitriadis

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)

Abstract

Preeclampsia is a serious pregnancy-induced disorder unique to humans. The etiology of preeclampsia is poorly understood; however, poor placental formation is thought causal. Galectin-7 is produced by trophoblast and is elevated in first-trimester serum of women who subsequently develop preeclampsia. We hypothesized that elevated placental galectin-7 may be causative of preeclampsia. Here, we demonstrated increased galectin-7 production in chorionic villous samples from women who subsequently develop preterm preeclampsia compared with uncomplicated pregnancies. In vitro, galectin-7 impaired human first-trimester trophoblast outgrowth, increased placental production of the antiangiogenic sFlt-1 splice variant, sFlt-1-e15a, and reduced placental production and secretion of ADAM12 (a disintegrin and metalloproteinase12) and angiotensinogen. In vivo, galectin-7 administration (E8-E12) to pregnant mice caused elevated systolic blood pressure, albuminuria, impaired placentation (reduced labyrinth vascular branching, impaired decidual spiral artery remodeling, and a proinflammatory placental state demonstrated by elevated IL1β, IL6 and reduced IL10), and dysregulated expression of renin-angiotensin system components in the placenta, decidua, and kidney, including angiotensinogen, prorenin, and the angiotensin II type 1 receptor. Collectively, this study demonstrates that elevated galectin-7 during placental formation contributes to abnormal placentation and suggests that it leads to the development of preeclampsia via altering placental production of sFlt-1 and renin-angiotensin system components. Targeting galectin-7 may be a new treatment option for preeclampsia.

Original languageEnglish
Pages (from-to)1185-1194
Number of pages10
JournalHypertension
Volume76
Issue number4
DOIs
Publication statusPublished - Oct 2020

Keywords

  • angiotensinogen
  • disintegrin
  • mice
  • placentation
  • pre-eclampsia

Cite this