Characterization of endoglin on mouse uterine stromal cells

During the oestrous cycle and early pregnancy the uterus undergoes a variet y of morphological and physiological modifications involving uterine cell p roliferation and differentiation as well as extensive tissue remodelling. T ransforming growth factor beta (TGF-beta) has powerful effects on these eve nts and thus is thought to have a critical role in uterine physiology. Endo glin is a transmembrane glycoprotein that binds TGF-beta 1 and -beta 3 and interacts with TGF-beta signalling receptors to modulate many effects of th is growth factor in different types of cell. Studies in mice revealed the h ighest concentrations of endoglin in the reproductive tract, notably on str omal cells of cyclic and pregnant uteri. The objective of the present study was to investigate the role of endoglin expressed on uterine stromal cells in binding TGF-beta and in the cellular responses induced by this growth f actor. Highly purified populations of uterine stromal cells were isolated b y cell affinity to the monoclonal antibody MJ7/18, which is specific to mou se endoglin. Affinity labelling of these cells with I-125-labelled TGF-beta followed by immunoprecipitation with endoglin-specific polyclonal 1256:4b antiserum indicated that endoglin expressed at the surface of uterine strom al cells binds TGF-beta 1 and interacts with TGF-beta signalling receptors. Treatment of uterine stromal cells with different concentrations of TGF-be ta 1 induced a biphasic proliferative response and addition of MJ7/18 as we ll as neutralizing TGF-beta antibodies showed endoglin to be a modulator of TGF-beta-induced stromal cell proliferation. Given the importance of TGF-b eta in the regulation of uterine physiology, these results indicate a role for endoglin during uterine tissue remodelling and decidualization.