Placenta · 2026
Esomeprazole treatment targeting sFLT-1 signaling in preeclampsia improves placental and fetal outcome in mice.
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Reisch Beatrix, Wölk Lilo Valerie, Edinger Alina, Kimmig Rainer, Iannaccone Antonella, Gellhaus Alexandra
Аннотация
INTRODUCTION: Preeclampsia (PE) is one of the leading causes of maternal and infant mortality. Increase of soluble fms-like tyrosine kinase-1 (sFLT-1) is thought to be a key player in pathophysiology. Since preclinical studies showed therapeutical effects of esomeprazole (Eso), we hypothesized treatment may target sFLT-1 in PE.
METHODS: Using the PE/FGR (fetal growth restriction) model with systemic human sFLT-1 overexpression, mice were treated with Eso or vehicle. We analyzed dams, fetal and placental tissues regarding sFLT-1 at day 18.5 dpc and determined hypoxia of placentas using the marker pimonidazole.
RESULTS: Eso led to a trend of decrease in sFLT-1 serum levels. As shown previously by us sFLT-1 increase resulted in different severity levels of FGR. Exclusive maternal sFLT-1 overexpression (PE wt) fetuses revealed a mild reduction in weights, combined maternal and feto-placental sFLT-1 (PE het) led to strong reductions in weights and non-viability of the fetuses. Upon Eso an improvement in fetal outcome shown by an increased rate of fetal viability and a significant increase in weight of PE het fetuses was observed. Furthermore, upon Eso sFLT-1 (sFLT-i13) mRNA expression significantly decreased in the mesometrial triangle tissue (MT) and in placentas of PE het fetuses and maternal kidneys. A significant decrease of pimonidazole in MT of PE wt fetuses and a trend of decrease in PE het fetuses upon Eso showed less hypoxia in the maternal compartment.
DISCUSSION: These results could indicate a potential cytoprotective effect of Eso and an improvement of the hypoxic conditions at the maternal-fetal interface during PE.
METHODS: Using the PE/FGR (fetal growth restriction) model with systemic human sFLT-1 overexpression, mice were treated with Eso or vehicle. We analyzed dams, fetal and placental tissues regarding sFLT-1 at day 18.5 dpc and determined hypoxia of placentas using the marker pimonidazole.
RESULTS: Eso led to a trend of decrease in sFLT-1 serum levels. As shown previously by us sFLT-1 increase resulted in different severity levels of FGR. Exclusive maternal sFLT-1 overexpression (PE wt) fetuses revealed a mild reduction in weights, combined maternal and feto-placental sFLT-1 (PE het) led to strong reductions in weights and non-viability of the fetuses. Upon Eso an improvement in fetal outcome shown by an increased rate of fetal viability and a significant increase in weight of PE het fetuses was observed. Furthermore, upon Eso sFLT-1 (sFLT-i13) mRNA expression significantly decreased in the mesometrial triangle tissue (MT) and in placentas of PE het fetuses and maternal kidneys. A significant decrease of pimonidazole in MT of PE wt fetuses and a trend of decrease in PE het fetuses upon Eso showed less hypoxia in the maternal compartment.
DISCUSSION: These results could indicate a potential cytoprotective effect of Eso and an improvement of the hypoxic conditions at the maternal-fetal interface during PE.