INTRAPLACENTAL PATHWAY MODULATING TROPHOBLAST CELLS

这项研究的长期目标是加深我们对妊娠的建立和维持的理解。我们主要关注起源于胎盘的信号分子的作用。催乳素(PRL)相关蛋白家族的成员在子宫胎盘间隔中以细胞和时间特异的模式表达，并已被证明在妊娠的建立和维持中发挥关键作用。催乳素样蛋白-C变异体(PLP-CV)是近年来发现的家族新成员。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表达。利用碱性磷酸酶(AP)-PLP-CV融合蛋白，我们发现PLP-CV仅与大鼠胎盘交界区内的滋养层巨细胞和海绵滋养层细胞结合。因此，产生PLP-CV的细胞也是PLP-CV的靶点，也是PLP-CV作用的靶点。我们推测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滋养层细胞系已被证明是研究滋养层细胞发育的一个非常有用的模型。我们建议利用Rcho-1滋养层细胞系作为体外模型来评价PLP-CV对滋养层细胞增殖和分化的影响。我们还将以AP-PLP-CV融合蛋白为探针，采用表达克隆策略分离PLP-CV的滋养层细胞受体。这些发现将进一步加深我们对胎盘内调节网络参与控制胎盘发育和维持妊娠的理解。

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.