TROPHOBLAST GENE EXPRESSION AND DIFFERENTIATION

胎盘在促进胎儿发育中有几个重要作用 发展。这个器官用来将发育中的胚胎植入 子宫的；作为交换营养物质和 排泄在母亲和胎儿之间的排泄物；作为防止 母体免疫系统对胎儿的攻击，防止 转移到胎儿循环中的危险化合物，如重 金属；作为调节母体和母体的分泌蛋白的来源 和胎儿生理学。关于最后一个角色，胎盘 有几个物种(包括啮齿动物、绵羊、奶牛和人类)是这个地点 在结构上与垂体相关的蛋白质的合成 催乳素。这些激素调节母体卵巢类固醇激素的生成 (诱导孕酮产生以维持妊娠)，肝脏 新陈代谢(从储存形式释放葡萄糖供胎儿使用)， 和乳房发育(为哺乳做准备)；这些激素还 进入胎儿隔室，在那里它们可能会对胎儿产生直接影响 在发展方面，例如在肺发育方面。在老鼠身上， 催乳素家族：胎盘中特异合成的蛋白质 包括胎盘催乳素I、胎盘催乳素II、增殖素和 增殖相关蛋白。我们建议将遗传元素定义为 调节滋养层细胞和时间特异性表达的这些 小鼠中的催乳素家族基因。最初的努力将集中在 胎盘催乳素I和增殖相关蛋白的活性 在细胞培养中，这些基因启动子中的一个是滋养层细胞特异性的。 转染法检测。胎盘催乳素I提供了进一步的优势 在怀孕早期表达，因此可能代表 转录/分化因子在早期作用的靶点 胎盘发育阶段；胎盘催乳素I基因启动子 因此也可以用来产生永生化的滋养层细胞 台词。与此同时，增殖相关蛋白提供了一种独特的 对小鼠滋养层细胞分化的处理，因为它在两个 滋养层细胞类型，不同于催乳素家族的其他成员。 瞬时转染啮齿动物绒毛膜癌细胞和 转基因小鼠的体内表达将被检测以确定这些 监管要素。定义后，这些元素将用于 确定一个跨代理监管因素(S)负责 这些基因在滋养层细胞中的表达。这一点的表达 在胎盘和胎儿发育过程中的因素，以及在成人中， 然后将接受调查。它的鉴定和表征 S因子将提供一种检测胎盘滋养层细胞的手段 分子水平上的分化。因为滋养层细胞 密切参与胚胎发育，识别基因 滋养层细胞分化及相关因子的研究进展 这一功能将有助于检测、预防和治疗出生缺陷。

The placenta functions in several important ways in promoting fetal development. This organ serves to implant the developing embryo in the uterus; as a conduit for the exchange of nutritional supplies and excreted waste between the mother and the fetus; as a barrier preventing attack on the fetus by the maternal immune system, and preventing transport into the fetal circulation of hazardous compounds such as heavy metals; and as a source of secreted proteins that regulate both maternal and fetal physiology. In regard to this last role, the placenta in several species (including rodents, sheep, cows, and humans) is the site of synthesis of proteins that are structurally related to pituitary prolactin. These hormones regulate maternal ovarian steroidogenesis (inducing progesterone production to maintain pregnancy), liver metabolism (to release glucose from storage forms for use by the fetus), and mammary development (to prepare for lactation); these hormones also enter the fetal compartment, where they may have direct effects on fetal development, for example in lung development. In the mouse, the prolactin family of proteins synthesized specifically in the placenta includes placental lactogen I, placental lactogen II, proliferin, and proliferin-related protein. We propose to define the genetic elements that regulate the trophoblast- and temporal-specific expression of these prolactin family genes in the mouse. Initial efforts will focus on placental lactogen I and proliferin-related protein, since the activity of these gene promoters is trophoblast-specific in cell culture transfection assays. Placental lactogen I provides the further advantage of being expressed early during gestation, and therefore may represent a target for a transcription/differentiation factor acting at an early stage of placental development; the placental lactogen I gene promoter will therefore also be used to generate immortalized trophoblast cell lines. The proliferin-related protein, meanwhile, provides a unique handle on mouse trophoblast differentiation since it is expressed in two trophoblast cell types, unlike the other members of the prolactin family. Both transient transfections into rodent choriocarcinoma cells and in vivo expression in transgenic mice will be assayed to define these regulatory elements. Once defined, these elements will then be used to identify a trans-acting regulatory factor(s) responsible for the expression of these genes in trophoblast cells. The expression of this factor during placental and fetal development, as well as in the adult, will then be investigated. Identification and characterization of this factor(s) will provide a means to examine placental trophoblast cell differentiation on a molecular level. Since the trophoblast cells are intimately involved in embryonic development, identifying the genetic elements and factors involved in trophoblast cell differentiation and function will aid in detecting, preventing, and treating birth defects.