Galectin-7 Impairs Placentation and Causes Preeclampsia Features in Mice.

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.

• Authors: 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
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 76 Issue 4 Pg. 1185-1194 (10 2020) ISSN: 1524-4563 [Electronic] United States
• PMID: 32862708 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Galectins
• LGALS7 protein, human
• ADAM12 Protein

Topics

• ADAM12 Protein (metabolism)
• Animals
• Blood Pressure (drug effects)
• Chorionic Villi (metabolism)
• Female
• Galectins (genetics, metabolism, pharmacology)
• Humans
• Mice
• Placentation (drug effects)
• Pre-Eclampsia (genetics, metabolism)
• Pregnancy
• Renin-Angiotensin System (drug effects)
• Trophoblasts (drug effects, metabolism)