Publication
Galectin-7 Impairs Placentation and Causes Preeclampsia Features in Mice
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Date:
10-2020
DOI:
10.1161/HYPERTENSIONAHA.120.15313
Abstract: Preecl sia is a serious pregnancy-induced disorder unique to humans. The etiology of preecl sia 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 preecl sia. We hypothesized that elevated placental galectin-7 may be causative of preecl sia. Here, we demonstrated increased galectin-7 production in chorionic villous s les from women who subsequently develop preterm preecl sia 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 preecl sia via altering placental production of sFlt-1 and renin-angiotensin system components. Targeting galectin-7 may be a new treatment option for preecl sia.