Preeclampsia (PE) is pregnancy-induced hypertension with proteinuria, and is often associated with fetal growth restriction (FGR). PE is a leading cause of maternal morbidity and mortality. Although alterations in circulating angiogenic factors are pathogenic, the details of pathological mechanisms of PE remain to be elucidated. We investigated changes in metabolites in a mouse model of PE induced by overproducing soluble fms-like tyrosine kinase 1 (sFlt-1) to elucidate the pathological conditions of PE by metabolomics analysis.Design and Method
: Recombinant adenovirus to overproduce sFlt-1 was administered to mice (C57BL/6) on 8.5 days post-coitum (dpc) to make PE model. Plasma and placenta samples were harvested at 12.5 dpc for metabolomics analysis by LC-MS and for gene expression analysis. BeWo cells were used to evaluate gene expressions in PE conditions.Results:
Blood pressure of a mouse model of PE was significantly increased, and the fetal weight was significantly decreased. Metabolomic analysis revealed that plasma and placental carnitine and acylcarnitines were significantly higher in PE model mice than controls. The mRNA expression of an organic cation transporter (OCTN2), a transporter of carnitines, was significantly increased in placentae from PE model mice and BeWo cells cultured in hypoxic condition.Conclusions:
The difference of carnitine and acylcarnitnes in placenta may contribute to pathological conditions of PE and FGR associated with PE.