Comparison of in vitro pre-eclampsia (PE) cell models with PE placental tissue

Abstract

Objectives: We induced hypoxia and oxidative stress (OS) in cytotrophoblasts (CTB) from control placentae to mimic the characteristics of preeclampsia (PE). For validation we compared the gene and protein expression of established PE biomarkers between the cell models and PE placentae. Methods: CTB isolated from healthy term placentae (n¼2) were cultured either under normoxic (5% pCO2;21% pO2;24h), hypoxic (5% pCO2;1.5% pO2;24h) or OS (consecutive 6h-intervals of normoxia and hypoxia until 24h) conditions. mRNA abundances of PE biomarkers (Table1) were analysed by qRT-PCR in the cell models and PE placentae (n¼12). Additionally, the secretion of sFlt1 and PlGF was determined by ELISA in cell culture supernatants. Statistical analysis was performed using unpaired t-test. Results: The cell models recapitulated important pathophysiological changes occurring in PE (Table1) including the upregulation of sFlt1 which was also observed in PE placentae. Interestingly, in the cell models the sFlt1/PlGF ratio was above the clinically applied cutoff value of 38 for hypoxic (77.3±35.2) and OS (124±88.3), but <38 for normoxic (19.4±16) conditions. nm-not measured Conclusion: The established cell models are mimicking important characteristics of PE. The sFlt1/PlGF ratio obtained in cell models is in agreement with reports proposing sFlt1/PlGF as predictive diagnostic marker for PE. Thus, hypoxia and OS induced in primary CTB can serve as suitable models to study the detailed mechanisms of PE.