We have developed an in vivo model for studying human utero-vaginal development in the presence and absence of the teratogenic drug, diethylstilbestrol (DES). This investigation will study the normal sequence of morphogenetic development and cytodifferentiation in the human female reproductive tract and the mechanisms by which prenatal exposure to DES alters the normal growth process. Intact reproductive tracts from human embryos and fetuses approximately 5 through 18 postovulatory weeks will be grown in vivo in athymic (nude) mice which are untreated (control) or implanted subcutaneously with a DES pellet. Studies in human will address 1) the origin of vaginal epithelium (Mullerian vs. urogenital sinus), 2) the long-term effects (and their possible reversibility) of exogenous estrogens on the developing reporductive tract), 3)the mechanism by which DES suppresses development of the uterus, which in the exposed (abnormal) state is associated clinically with increased rates of pregnancy wastage, and 4) screen drugs, such as 17-hydroxyprogesterone caproate, currently given to pregnant mothers, for the possible teratogenic effects on the developing human genital tract. A second broad phase of this study will address the mechanisms by which estrogens induce growth. Through a combination of steroid autoradiography (using in vivo and in vitro techniques), biochemical analysis, transfilter techniques, and electron microscopy, studies in mice will address 1) how mesenchymal cells in the uterus, which at an early stage exhibit estrogen-receptor activity, are involved in and possibly responsible for the subsequent differentiation of the uterine epithelium and its development of estrogen-receptor activity. 2) whether hormones stimulate the epithelial grown directly or indirecly via non-steroidal grown factors elaborated by the mesenchyme, and 3) whether a model can be constructed to determine if the mesenchyme influences epithelial grownth by secreting a diffusible inductor molecule, establishing cell contract (stroma-epithelial junctions), or through cell contract-extracellular matrix interactions (via basement membrane).