Galectin-7 Impairs Placentation and Causes Preeclampsia Features in Mice

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 76; no. 4; pp. 1185 - 1194
• Main Authors: Menkhorst, Ellen, Zhou, Wei, Santos, Leilani L, Delforce, Sarah, So, Teresa, Rainczuk, Kate, Loke, Hannah, Syngelaki, Argyro, Varshney, Swati, Williamson, Nicholas, Pringle, Kirsty, Young, Morag J, Nicolaides, Kypros H, St-Pierre, Yves, Dimitriadis, Eva
• Format: Journal Article
• Language: English
• Published: United States American Heart Association, Inc 01.10.2020
• Subjects: ADAM12 Protein - metabolism; Animals; Blood Pressure - drug effects; Chorionic Villi - metabolism; Female; Galectins - genetics; Galectins - metabolism; Galectins - pharmacology; Humans; Mice; Placentation - drug effects; Pre-Eclampsia - genetics; Pre-Eclampsia - metabolism; Pregnancy; Renin-Angiotensin System - drug effects; Trophoblasts - drug effects; Trophoblasts - metabolism; disintegrin; placentation; pre-eclampsia; angiotensinogen; mice
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.120.15313

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.