Research using the primary cell culture of trophoblasts to clarify how is the differentiation of trophoblasts regulated

足够的细胞滋养层（CT）分化和随后的重塑母体子宫血管是建立子宫胎盘循环的关键。在包括CT在内的胎盘细胞中证实了血管内皮生长因子（VEGF）家族分子的产生。然而，还没有阐明CT的分化沿着其功能的改变，特别是CT中的VEGF系统如何受胎盘中的局部环境如氧分压和母体免疫细胞的控制，以及它如何参与胎盘循环的发育。为了解决这一问题，我们探讨了氧张力和母体免疫细胞对VEGF及其拮抗剂，可溶性fms样酪氨酸激酶-1（sFlt-1）的表达的影响，使用原代CT培养系统。氧气减少导致CT中sFlt-1产量显著增加，而其他胎盘细胞中并非如此。VEGF的产生也受到CT中氧气减少的刺激， ...更多信息 低于sFlt-1产量。这些结果表明，CT具有独特的性能，以提高sFlt-1生产在减少氧气，因此可以拮抗血管生成活性的VEGF。对于母体免疫细胞，与未活化的淋巴细胞相比，经蜕膜淋巴因子激活的杀伤（LAK）细胞预处理的CT释放更多的sFlt-1。无论是活化或非活化蜕膜淋巴细胞（DMC）的预处理，从CT的VEGF的生产没有改变。在子痫前期胎盘组织中，IL-2诱导的LAK细胞可与CTs发生反应，促进CTs释放sFlt-1，而不影响VEGF的分泌。这可能导致蜕膜中VEGF系统的实际血管生成潜力降低，胎盘血管系统可能受损，这可能导致胎盘缺氧，胎盘缺氧可能通过分泌更多的sFlt-1而进一步拮抗胎盘血管系统，从而发展为先兆子痫。少

Sufficient cytotrophoblasts (CTs) differentiation and subsequent remodeling of maternal uterine vasculature is critical to establish uteroplacental circulation. The production of vascular endothelial growth factor (VEGF) family molecules is confirmed in placental cells including CTs. However, it is not elucidated how the differentiation of CTs along with the alteration of their function, especially VEGF system in CTs, is controlled by local environment in placenta such as oxygen tension and maternal immune cells, and how it is involved in the development of placental circulation. To address this, we explored the effect of oxygen tension and maternal immune cells on the expression of VEGF and its antagonist, soluble fms-like tyrosine kinase-1 (sFlt-1) using a primary CT culture system. Reduced oxygen resulted in a pronounced increase in sFlt-1 production in CTs, whereas this was not the case in other placental cells. VEGF production was also stimulated by reduced oxygen in CTs but much … More less than sFlt-1 production. These results implicate that CTs possess a unique property to enhance sFlt-1 production under reduced oxygen, which could consequently antagonize angiogenic activity of VEGF. As for maternal immune cells, CTs pretreated with decidual lymphokine-activated killer (LAK) cells released more sFlt-1 compared with those pretreated with non-activated lymphocytes. The production of VEGF from CTs was not altered by pretreatment with either activated or non-activated decidual lymphocytes(DMCs). In preeclamptic placenta, LAK cells induced from DMCs by co-existing IL-2 may react to the CTs and enhance the release of sFlt-1 from CTs without any change of VEGF secretion. This might result in the reduction of actual angiogenic potential of the VEGF system in decidua and the placental vascular system might be compromised, which may lead to the hypoxia in placenta and hypoxia in placenta might further antagonize the placental vasculature by secreting more sFlt-1 and develop preeclampsia. Less