- Title
- Galectin-7 Impairs Placentation and Causes Preeclampsia Features in Mice
- Creator
- Menkhorst, Ellen; Zhou, Wei; Pringle, Kirsty; Young, Morag J.; Nicolaides, Kypros H.; St-Pierre, Yves; Dimitriadis, Evdokia; Santos, Leilani L.; Delforce, Sarah; So, Teresa; Rainczuk, Kate; Loke, Hannah; Syngelaki, Argyro; Varshney, Swati; Williamson, Nicholas
- Relation
- NHMRC .GNT1098332 http://purl.org/au-research/grants/nhmrc/1098332
- Relation
- Hypertension Vol. 76, Issue 4, p. 1185-1194
- Publisher Link
- http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15313
- Publisher
- Lippincott Williams & Wilkins
- Resource Type
- journal article
- Date
- 2020
- Description
- 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.
- Subject
- mice; pre-eclampsia; angiotensinogen; disintegrin; placentation
- Identifier
- http://hdl.handle.net/1959.13/1441445
- Identifier
- uon:41424
- Identifier
- ISSN:0194-911X
- Language
- eng
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