Inducible knockout of Syncytin-A gene leads to an extensive placental vasculature deficiency, implications for preeclampsia.

Syncytin-1, a human endogenous retroviral envelope gene (HERVW1), is specifically expressed in placental trophoblasts and mediates the formation of syncytiotrophoblasts through a fusogenic activity. Syncytin-1 expression deficiency has been repeatedly observed in preeclamptic/IUGR placentas. Previous gene knockout studies indicated that in mice, complete syncytin-A null mouse embryos died in utero between 11.5 and 13.5days of gestation. However, the complete knockout model could not fully recapitulate the mid- to third-trimester, time-specific syncytin-1 deficiency in preeclampsia patients. To construct a preeclampsia model and to better investigate the function of syncytin in placental development, we created a mouse inducible knockout model of syncytin-1A gene. It was found that the disruption of syncytin-A at E11.5 to E17.5 is associated with significant morphological changes in placentas and fetuses. Moreover, syncytin-A disruption led to extensive vasculature abnormalities in the labyrinth, with irregular distribution and reduced number of fetal microvessels. Moreover, Syncytin-A knockout affected neovascularization-related gene expression in labyrinth and the maternal plasma level of sVEGFR-1, and a dramatic increase of sFlt-1/PlGF ratio. These findings indicate that syncytin-A may be involved in the placenta angiogenesis and potentially, the development of preeclampsia. The new model could be a useful tool for studying the pathogenesis and management of preeclampsia.

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