INTRAPLACENTAL PATHWAY MODULATING TROPHOBLAST CELLS

这项研究的长期目标是进一步加深我们对怀孕的建立和维持的理解。我们关注的是源自胎盘的信号分子的作用。与催乳素（PRL）相关的蛋白家族成员在子宫胎盘间室中以细胞和时间特异性模式表达，并已被证明在妊娠的建立和维持中发挥关键作用。Prolactin-like protein-C variant （PLP-Cv）是近年来发现的新成员。在妊娠后半期大鼠胎盘的滋养层巨细胞和海绵状滋养层细胞中特异性表达。利用碱性磷酸酶(AP)-PLP-Cv融合蛋白，我们发现PLP-Cv只与大鼠胎盘交界区滋养层巨细胞和海绵滋养层细胞结合。因此，产生PLP-Cv的细胞同时也是PLP-Cv的靶标，也是PLP-Cv作用的靶标。我们假设PLP-Cv可能是一种参与胎盘发育/功能调节的自分泌/旁分泌因子。Rcho-1滋养细胞系已被证明是研究滋养细胞发育的一个非常有用的模型。我们拟利用Rcho-1滋养细胞作为体外模型，研究PLP-Cv对滋养细胞增殖和分化的影响。我们还将使用以AP- PLP-Cv融合蛋白为探针的表达克隆策略分离PLP-Cv的滋养细胞受体。这些发现将进一步加深我们对胎盘发育和妊娠维持的调控网络的理解。

The long-term objective of the research is to further our understanding of the establishment and maintenance of pregnancy. We focus on the actions of signaling molecules originating in the placenta. Members of a family of proteins related to prolactin (PRL) are expressed in cell- and temporal- specific patterns in the uteroplacental compartment and have been shown to play a pivotal role in the establishment and maintenance of pregnancy. Prolactin-like protein-C variant (PLP-Cv) is new member of the family identified in recent years. It is expressed specifically in trophoblast giant cells and spongiotrophoblast cells of the rat placenta during the second half of gestation. Using an alkaline phosphatase (AP)-PLP-Cv fusion protein, we found that PLP-Cv exclusively bound to trophoblast giant cells and spongiotrophoblast cells within the junctional zone of the rat placenta. Thus, the same cells that produce PLP-Cv are also targets for PLP-Cv are also targets for PLP-Cv action. We hypothesize that PLP-Cv may be an autocrine/paracrine factor involved in the regulation of placental development/function. The Rcho-1 trophoblast cell lines has been proven to be a very useful model to investigate trophoblast cell development. We propose to utilize the Rcho-1 trophoblast cell line as an in vitro model to evaluate the effects of PLP-Cv on trophoblast cell proliferation and differentiation. We will also isolate the trophoblast cell receptor for PLP-Cv using an expression cloning strategy with the AP- PLP-Cv fusion protein as a probe. These findings will further our understanding of the intraplacental regulatory network involved in the control of placental development and maintenance of pregnancy.