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Galectin-7 Impairs Placentation and Causes Preeclampsia Features in Mice
Ellen Menkhorst1,2,3, Wei Zhou1,2, Leilani L Santos1,2
1From the Department of Obstetrics and Gynaecology, The University of Melbourne, Parkville, VIC, Australia (E.M., W.Z., L.L.S., T.S., E.D.).
Hypertension (Dallas, Tex. : 1979)
|September 1, 2020
Summary
Elevated galectin-7 in early pregnancy contributes to preeclampsia by impairing placental development and altering key molecular pathways. Targeting galectin-7 may offer a novel therapeutic strategy for this serious pregnancy disorder.
Area of Science:
- Reproductive biology
- Maternal-fetal medicine
- Immunology
Background:
- Preeclampsia is a severe human pregnancy disorder with unknown causes, often linked to poor placental development.
- Galectin-7, a protein produced by trophoblast cells, is found at higher levels in early pregnancy serum of women who later develop preeclampsia.
Purpose of the Study:
- To investigate the hypothesis that elevated placental galectin-7 is a causative factor in preeclampsia development.
- To elucidate the mechanisms by which galectin-7 may contribute to preeclampsia pathophysiology.
Main Methods:
- Analysis of chorionic villous samples from preeclamptic and uncomplicated pregnancies.
- In vitro studies using human trophoblast cells to assess galectin-7 effects on cell outgrowth, sFlt-1, ADAM12, and angiotensinogen production.
- In vivo studies administering galectin-7 to pregnant mice to evaluate effects on blood pressure, proteinuria, placentation, and renin-angiotensin system components.
Main Results:
- Increased galectin-7 production in placentas of women who developed preterm preeclampsia.
- In vitro, galectin-7 impaired trophoblast outgrowth, increased antiangiogenic sFlt-1 (sFlt-1-e15a), and decreased ADAM12 and angiotensinogen.
- In vivo, galectin-7 administration induced preeclampsia-like symptoms in mice, including hypertension, albuminuria, impaired placentation, and dysregulated renin-angiotensin system components.
Conclusions:
- Elevated galectin-7 during early placental formation contributes to abnormal placentation and preeclampsia development.
- Galectin-7 appears to mediate preeclampsia by altering placental production of sFlt-1 and renin-angiotensin system components.
- Targeting galectin-7 presents a potential new therapeutic avenue for preeclampsia.
