Galectin-7 Impairs Placentation and Causes Preeclampsia Features in Mice
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.
| Errataetall: |
CommentIn: Hypertension. 2020 Oct;76(4):1087-1089. - PMID 32903108 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:76 |
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| Enthalten in: |
Hypertension (Dallas, Tex. : 1979) - 76(2020), 4 vom: 01. Okt., Seite 1185-1194 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Menkhorst, Ellen [VerfasserIn] |
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| Links: |
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| Themen: |
ADAM12 Protein |
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| Anmerkungen: |
Date Completed 30.04.2021 Date Revised 12.05.2021 published: Print-Electronic CommentIn: Hypertension. 2020 Oct;76(4):1087-1089. - PMID 32903108 Citation Status MEDLINE |
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| doi: |
10.1161/HYPERTENSIONAHA.120.15313 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM314358366 |
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| 500 | |a CommentIn: Hypertension. 2020 Oct;76(4):1087-1089. - PMID 32903108 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
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| 700 | 1 | |a Zhou, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Santos, Leilani L |e verfasserin |4 aut | |
| 700 | 1 | |a Delforce, Sarah |e verfasserin |4 aut | |
| 700 | 1 | |a So, Teresa |e verfasserin |4 aut | |
| 700 | 1 | |a Rainczuk, Kate |e verfasserin |4 aut | |
| 700 | 1 | |a Loke, Hannah |e verfasserin |4 aut | |
| 700 | 1 | |a Syngelaki, Argyro |e verfasserin |4 aut | |
| 700 | 1 | |a Varshney, Swati |e verfasserin |4 aut | |
| 700 | 1 | |a Williamson, Nicholas |e verfasserin |4 aut | |
| 700 | 1 | |a Pringle, Kirsty |e verfasserin |4 aut | |
| 700 | 1 | |a Young, Morag J |e verfasserin |4 aut | |
| 700 | 1 | |a Nicolaides, Kypros H |e verfasserin |4 aut | |
| 700 | 1 | |a St-Pierre, Yves |e verfasserin |4 aut | |
| 700 | 1 | |a Dimitriadis, Eva |e verfasserin |4 aut | |
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