Lipid species impairment in preeclampsia driven by niche specific deficiency of galectin-1.

BRUNING U ; GARCIA MG; URBAN I; FREITAG N; MICHEL G; BLOIS SM; KIRWAN J

Conferencia; Lipidomics Gordon Research Conference; 2022

Preeclampsia (PE) is a serious disease that develops during pregnancy leading to hypertension and prolonged cardiovascular risk. It is also associated with substantial maternal and fetal morbidity and mortality. Galectin-1 (gal-1), a glycan-binding protein that gradually increases during pregnancy, has been identified as a key modulator promoting placenta development, angiogenesis and maternal immune tolerance towards paternal antigens. Dysregulation of gal-1 is correlated with the development of PE in humans and mice and it is linked to impaired angiogenesis and maternal immune adaptation. To further analyze the metabolic consequences of gal-1 deregulation during pregnancy we generated niche specific KO mice (WT, maternal KO, Placental KO and full KO) and focus on the lipidome analysis before PE onset (E13). Whereas systemic lipid levels were largely decreased among different lipid classes in full KO mice compared to WT mice, placenta and decidua lipids showed distinct and tissue specific patterns of various lipid classes. Cholesterol esters, diacylglycerols and ceramides (bioactive lipid species in inflammation) are decreased in the decidua of full KO mice but increased within placenta niche. In contrast, triacylglycerols were only elevated in the decidua derived from full KO mice up to 19% compared to 3% in the other groups, indicating their great contribution to tissue rearrangement in PE. Differential lipid composition is accompanied by a systemic inflammation as evidenced by elevated levels of systemic TNF-alpha in full KO mice. Thus, the identification of tissue specific lipid rearrangements helps understanding the mechanisms of preeclampsia development and might define further biomarker to characterize this life-threatening disease in the clinics.