TROPHOBLAST GENE EXPRESSION AND DIFFERENTIATION

胚胎外滋养层细胞的分化是关键 哺乳动物胚胎植入的第一步。滋养层细胞 通过连接母体和胚胎的隔间 子宫蜕膜细胞，侵袭母体血管和接触 母体血液，并分泌调节母体和胎儿的激素 生理学。在啮齿动物中，形成周围的滋养层细胞 植入部位的胚胎室被称为巨型。 细胞。这些细胞是通过消灭正常细胞而产生的。 循环与DNA重复循环程序的建立 没有细胞分裂的合成。从二倍体转化为二倍体 假设滋养层细胞转变为巨细胞是由因素诱导的。 这也调节滋养层巨细胞特异性基因的表达。 两个这样的转录因子是GATA-2和GATA-3。实验 是为了测试GATA-2和GATA-3是否 从增殖性滋养层细胞转变为 终末分化的巨细胞在培养中的调节作用 胎盘在体内发育。滋养层细胞将被操纵 在培养和体内增加或降低GATA因子活性， 这些变化对细胞分化和 将对发展进行审查。此外，尽管GATA-2和GATA- 3在一组有限的细胞类型中表达，它们不是 仅在滋养层巨细胞中表达。因此，巨型细胞- 依赖于GATA因子活性的特定基因表达必须 也依赖于其他转录调节蛋白。三 AP-1、HXT和P53等因子将作为成分与 巨型细胞专用组合码的GATA-2和GATA-3 基因表达。最后，巨型细胞还会进一步 妊娠期间的分化，如光谱所揭示的 它们分泌荷尔蒙。这种中晚期妊娠的发生机制 分化可能取决于转录水平的变化。 巨细胞中存在激活物或抑制物，所以元素和 妊娠中期/晚期与妊娠早期/中期相比的影响因素 将分析巨细胞基因的表达情况。

Differentiation of the extra-embryonic trophoblasts is the essential first step for implantation of the mammalian embryo. Trophoblasts connect the maternal and embryonic compartments by attaching to uterine decidual cells, invade maternal blood vessels and contact maternal blood, and secrete hormones that regulate maternal and fetal physiology. In rodents, the trophoblasts that form the perimeter of the embryonic compartment at the implantation site are called giant cells. These cells arise through an abrogation of the normal cell cycle and the establishment of a program of repeated rounds of DNA synthesis without cell division. The transformation from a diploid trophoblast to a giant cell is hypothesized to be induced by factors that also regulate trophoblast giant cell-specific gene expression. Two such transcription factors are GATA-2 and GATA-3. Experiments are proposed to test the possibility that GATA-2 and GATA-3 are determinants in the switch from proliferative trophoblasts to terminally differentiated giant cells in culture, and regulators of placental development in vivo. Trophoblast cells will be manipulated in culture and in vivo to increase or decrease GATA factor activity, and the consequence of these changes on cell differentiation and development will be examined. Furthermore, although GATA-2 and GATA- 3 are expressed in a restricted set of cell types, they are not expressed exclusively in trophoblast giant cells. Thus, giant cell- specific gene expression, which depends on GATA factor activity, must also depend on other transcriptional regulatory proteins. Three factors, AP-1, Hxt, and p53, will be tested as components along with GATA-2 and GATA-3 of a combinatorial code for giant cell-specific gene expression. Finally, giant cells undergo further differentiation during gestation as revealed by the spectrum of hormones they secrete. The mechanism of this mid-to late-gestation differentiation is likely to depend on changes in the transcriptional activators or repressors present in giant cells, so the elements and factors responsible for mid/late compared to early/mid pregnancy giant cell gene expression will be analyzed.