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.
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