Analyses of regulation mechanisms which induce invasion of human extravillous troophoblasts toward maternal uterine spiral arteries.

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BackgroundDuring human placentation, embryo-derived trophoblasts differentiate into villous trophoblasts and extravilous trophoblasts (EVT). EVTs invade into maternal endometria and vessel walls of uterine spiral arteries, which results in decreased vascular resistance of utero-placental circulation. Previously, we analyzed the mechanisms of regulated invasion of EVTs into maternal endometria and myometria, and found that EVTs around maternal spiral arteries might retain invasive phenotype compared with EVTs in myometrial layer. From this finding, we speculated that EVTs might be induced to invade toward maternal spiral arteries and factors derived from maternal immune cells might be one of candidates. Therefore in this project, we analyzed the role of maternal immune cell derived factors on the regulation mechanisms of human EVT invasion toward maternal uterine spiral arteries.Results1)Chemokine receptors are expressed in human EVTsBy RT-PCR analyses, cultured human EVTs were found to … More express various chemokine ceceptors, CCR1, CCR10 and XCR1. Among these chemokine receptors, immunohistochemical analyses confirmed that CCR1 was specifically expressed on EVTs around maternal spiral arteries but not on EVTs in myometrial layer.2) RANTES enhances the invasive property of human EVTsImmunohistochemical analyses showed that RANTES, one of ligands for CCR1, were expressed in immune cells around maternal spiral arteries. In addition, invasiveness of cultured human EVTs were enhanced in the presence of recombinant RANTES.3)Hypoxia and decidual factor attenuated CCR1 expression in human EVTsBy Northen blot analyses, culture of human EVTs in hypoxic condition attenuated the CCR1 expression. In addition, co-culture of human EVTs with maternal decidual tissue also attenuated the CCRI expression in human EVTs.ConclusionsOxygen concentration around maternal spiral arteries is higher than deep myometrial layer, which suggests that EVTs around maternal spiral arteries might retain CCR1 expression. Because RANTES enhances the invasive property of CCR1-expressing human EVTs, the interaction of RANTES and CCR1 might be one factor which induce human EVTs toward maternal spiral arteries. Less