1. Placental glycosylation senses the anti-angiogenic milieu induced by human sFLT1 during pregnancy.
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Kirkgöz, Kürsat, Vogtmann, Rebekka, Xie, Yiran, Zhao, Fangqi, Riedel, Alina, Adam, Lisa-Marie, Freitag, Nancy, Harms, Charlotte, Garcia, Mariana G., Plösch, Torsten, Gellhaus, Alexandra, and Blois, Sandra M.
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PLACENTA , *PLACENTA praevia , *PREGNANCY , *GLYCOSYLATION , *PLACENTA diseases , *GALECTINS , *DECIDUA - Abstract
Abnormal placental angiogenesis during gestation resulting from high levels of anti-angiogenic factors, soluble fms-like tyrosine kinase-1 (sFLT1) and soluble endoglin, has been implicated in the progression of preeclampsia (PE). This heterogeneous syndrome (defined by hypertension with or without proteinuria after 20 weeks of pregnancy) remains a major global health burden with long-term consequences for both mothers and child. Previously, we showed that in vivo systemic human (hsFLT1) overexpression led to reduced placental efficiency and PE-like syndrome in mice. Galectins (gal-1, −3 and −9) are critical determinants of vascular adaptation to pregnancy and dysregulation of the galectin-glycan circuits is associated with the development of this life-threatening disease. In this study, we assessed the galectin-glycan networks at the maternal-fetal interface associated with the hsFLT1-induced PE in mice. We observed an increase on the maternal gal-1 expression in the decidua and junctional zone layers of the placenta derived from hs FLT1high pregnancies. In contrast, placental gal-3 and gal-9 expression were not sensitive to the hsFLT1 overexpression. In addition, O- and N-linked glycan expression, poly-LacNAc sequences and terminal sialylation were down-regulated in hsFLT1 high placentas. Thus, the gal-1-glycan axis appear to play an important role counteracting the anti-angiogenic status caused by sFLT1, becoming critical for vascular adaptation at the maternal-fetal interface. • Anti-angiogenic milieu induced by human soluble fms-like tyrosine kinase-1 (hsFLT1) alters the galectin-glycan circuits during pregnancy. • Decidual gal-1 is upregulated in hsFLT1 induced Preeclampsia (PE)-like syndrome in mice. • hsFLT1 exerts a strong influence on the O- and N-linked glycan expression, poly-LacNAc sequences and terminal sialylation at the maternal-fetal interface. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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