The research proposed here is designed to examine two hypotheses: (a) that progesterone-induced differentiation of human endometrium results in the secretion of two distinct sets of proteins, the first synthesized by the glandular epithelium and the second, by decidualized stromal cells, and (b) that specific proteins produced by the secretory endometrium are locally acting, paracrine hormones that influence the growth or function of the trophoblast. An initial series of experiments will characterize primary cultures of stromal, decidual, and epithelial cells prepared from human endometrium. The effects of estradiol and progesterone on these cultures will be evaluated using cell morphology and the synthesis of specific proteins as indices of differentiation. The major proteins secreted by each cell type under each hormonal treatment will be identified by one and two dimensional gel electrophoresis. The possible effects of endometrial cells on trophoblast will be examined in mixed cultures. If these experiments indicate that media conditioned by endometrial cells contain proteins that alter proliferation, protein synthesis, steroid production, or the morphology of the trophoblast, then attempts will be made to identify the active factor(s). These studies will provide new data about the response of cultured endometrial cells to steroid hormones in terms of both morphological differentiation and the production of secretory products and may lead to the identification of specific proteins that regulate development of the trophoblast during implantation.
