FUNCTION OF THE DECIDUAL TISSUE

本项目的总体目标是审查控制和作用 蜕膜组织在维持大鼠妊娠中的作用。 第一个目标 将决定bFGF是否是导致血管生成的原因 发生在着床和蜕膜化部位，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控制。 一 蜕膜化的形态学标志是 基质细胞分化成两个不同的细胞群， 子宫的系膜和反系膜区域。 由于TGF α 和EGF受体，通过其TGF α刺激细胞分化， 在蜕膜组织中表达，提出实验来确定 是否：1）子宫内膜的分化和可能的细胞增殖 基质细胞由TGF α诱导，以及2）免疫中和 TGF α的表达可以阻止外源性给药的 非转化细胞上的TGF α和内源性形成的生长因子 在转化的细胞中。 TGF α和/或EGF 受体表达受卵巢类固醇调节， 将审查蜕膜化的先决条件。 因为基质细胞 分化首先发生在子宫的反肠系膜区域， 仅仅几天后，在子宫系膜区域，颞叶 将评估两种组织中TGF α和EGF受体的表达 在整个蜕膜的发育过程中。 本建议的第二个目的是 将检验蜕膜组织退化是由于 程序性细胞死亡或凋亡的形式，更具体地说，1）是否 细胞死亡伴随着DNA断裂和核酸内切酶的增加 活性，2）编码核酸内切酶的新基因是否在 蜕膜细胞消退，以及3）是否孕酮和孕酮 受体在蜕膜程序性细胞死亡中起作用。 第三个目标 这项建议是为了进一步了解分泌和行动， 蜕膜激素 这将研究蜕膜的生理作用， 卵泡抑素是一种在蜕膜中大量表达的FSH抑制剂， 卵泡分泌雌二醇和蜕膜促黄体激素， α 2巨球蛋白的子宫系膜表达。 α 2巨球蛋白是一种 一种有效的蛋白酶抑制剂，在 限制滋养层细胞侵入。 最后一个具体目标建议， 建立稳定功能性系膜和抗系膜细胞系 细胞，以减少使用的动物数量，并获得 无限数量的子宫分泌细胞，无论是子宫系膜或 子宫反膜

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.