FUNCTION OF THE DECIDUAL TISSUE

这个项目的总体目标是检查控制和作用 蜕膜组织在维持大鼠妊娠中的作用。第一个目标 将确定碱性成纤维细胞生长因子是否对强烈的血管生成负责 这发生在孕育和蜕膜化的地方，无论是 由血管周围蜕膜细胞和/或内皮细胞产生， 以及它的合成是否受卵巢类固醇的控制。一个 蜕膜化的形态特征是 基质细胞分化为两个不同的细胞群，定位于 子宫的子宫系膜和反子宫系膜区域。由于两者都是TGFAlpha 和EGF受体，TGFpha通过它刺激细胞分化， 都在蜕膜组织中表达，建议进行实验以确定 是否：1)子宫内膜分化和可能的细胞增殖 基质细胞是由转化生长因子α诱导的，以及2)免疫中和 能阻止两者外源性给药的作用 未转化细胞和内源性生长因子的转化生长因子α 在转化的细胞中。转化生长因子α和/或表皮生长因子 受体的表达受卵巢类固醇的调节，这些类固醇是 将审查去非女性化的先决条件。因为基质细胞 分化首先发生在子宫的反子宫上皮区， 仅仅几天后，在子宫系膜区域， 将评估这两种组织中TGFα和EGF受体的表达 在蜕膜的发育过程中。这项提议的第二个目的是 将检验蜕膜组织退化是由于 细胞死亡或凋亡的程序化形式，更具体地说，1) 细胞死亡伴随着DNA片段化和核酸内切酶升高 活性，2)编码内切酶的新基因是否在 蜕膜细胞退化；3)孕酮和孕酮 受体在蜕膜细胞程序性死亡中发挥作用。第三个目标是 这项建议是为了进一步深入了解 蜕膜激素。这将检验蜕膜的生理作用。 FSH抑制因子FLISTION在蜕膜中大量表达 卵泡分泌雌二醇和蜕膜促黄体生成素 子宫系膜组织中α2巨球蛋白的表达。α2巨球蛋白是一种 一种强有力的蛋白水解酶抑制剂，它似乎在 限制滋养层细胞侵袭。最后一个具体目标建议 建立稳定的功能正常的子宫系膜和抗子宫系膜细胞系 细胞，以减少使用的动物数量，并获得 无限数量的激素分泌细胞，无论是子宫系膜还是 反子宫肌层。

The overall goal of this project is to examine the control and the role of decidual tissue in the maintenance of pregnancy in the rat. The first aim will determine whether bFGF is responsible for the intense angiogenesis that takes place in the site of nidation and decidualization, whether it is produced by either perivascular decidual cells and/or endothelial cells, and whether its synthesis is controlled by ovarian steroids. A morphological hallmark of decidualization is a striking transformation of stromal cells into two different cell populations localized in the mesometrial and antimesometrial region of the uterus. Since both TGFalpha and EGF receptors, through which TGFalpha stimulates cell differentiation, are expressed in the decidual tissue, experiments are proposed to determine whether: 1) differentiation and possibly cell proliferation of endometrial stromal cells are induced by TGFalpha, and whether 2) immunoneutralization of TGFalpha can prevent the action of both exogenously administered TGFalpha on nontransformed cells and the endogenously formed growth factor in transformed cells. The possibility that either TGFalpha and/or EGF receptor expression is regulated by ovarian steroids, which are prerequisites for decidualization, will be examined. Because stromal cell differentiation occurs first in the antimesometrial region of the uterus, and only several days later in the mesometrial region, the temporal expression of TGFalpha and EGF receptors in both tissues will be assessed throughout the development of the decidua. The second aim of this proposal will test the hypothesis that decidual tissue regression is due to a programmed form of cell death or apoptosis, more specifically, 1) whether cell death is accompanied by DNA fragmentation and increased endonuclease activity, 2) whether new genes encoding endonucleases are expressed during decidual cell regression, and 3) whether progesterone and progesterone receptors play a role in decidual programmed cell death. The third aim of this proposal is to gain further insight into the secretion and action of decidual hormone. This will examine the physiological role of decidual follistation, a FSH-inhibitor expressed abundantly in the decidua, on follicular secretion of estradiol, and that of decidual luteotropin on mesometrial expression of alpha2 macroglobulin. Alpha2 macroglobulin is a potent protease inhibitor which appears to play an important role in limiting trophoblast cell invasion. The last specific aim proposes to establish a stable cell line of functional mesometrial and antimesometrial cells in order to reduce the number of animals used, and to obtain an unlimited number of hormone-secreting cells, either mesometrial or antimesometrial.