Abstract
ABSTRACTPre-eclampsia is a multifactorial pregnancy-associated disorder characterized by angiogenic dysbalance and systemic inflammation; however, animal models that combine these two pathophysiological conditions are missing. Here, we introduce a novel double-hit pre-eclampsia mouse model that mimics the complex multifactorial conditions present during pre-eclampsia and allows for the investigation of early consequences for the fetus. Adenoviral overexpression of soluble fms-like tyrosine kinase (sFlt-1) and lipopolysaccharide (LPS) administration at mid-gestation in pregnant mice resulted in hypertension and albuminuria comparable to that of the manifestation in humans. A metabolomics analysis revealed that pre-eclamptic dams have increased plasma concentrations of phosphadytilcholines. The fetuses of both sexes were growth restricted; however, in males a brain-sparing effect was seen as compensation for this growth restriction. According to the plasma metabolomics, male fetuses showed changes in amino acid metabolism, while female fetuses showed pronounced alterations in lipid metabolism. Our results show that combined exposure to sFlt-1 and LPS mimics the clinical symptoms of pre-eclampsia and affects fetal growth in a sex-specific manner, with accompanying metabolome changes.
Highlights
Pre-eclampsia is a multisystemic pregnancy-associated disorder that is identified after the 20th week of gestation with the onset of hypertension and proteinuria (Mol et al, 2016)
Combined soluble fms-like tyrosine kinase 1 (sFlt-1) and lipopolysaccharide exposure induces pre-eclampsia symptoms in pregnant dams C57Bl/6J mice were subjected to adenoviral overexpression of sFlt1 and, 48 h later, challenged with lipopolysaccharide (LPS)
There were no differences in the number of pups, nor in the percentage of fetal resorptions between the groups (Fig. S1E,F). These data show that the midgestation double-hit exposure to sFlt-1 and LPS replicates the clinical features of human pre-eclampsia in pregnant dams
Summary
Pre-eclampsia is a multisystemic pregnancy-associated disorder that is identified after the 20th week of gestation with the onset of hypertension and proteinuria (Mol et al, 2016). It is one of the most frequent complications of pregnancy, affecting 3-7% of the population (Mol et al, 2016; Rajakumar et al, 2005). In up to 60% of cases, especially in early-onset pre-eclampsia, it is further complicated by fetal growth restriction (Weiler et al, 2011; Xiao et al, 2003). It has become apparent that pre-eclampsia shares characteristics with metabolic syndrome, at least through altered angiogenic and inflammatory markers (Salzer et al, 2015; Scioscia, 2017)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
