Transforming growth factor β1 exerts an autocrine regulatory effect on human endometrial stromal cell apoptosis, involving the FasL and Bcl-2 apoptotic pathways

Transforming growth factor beta1 (TGFbeta1) is expressed in human endometrium. It regulates epithelial cell proliferation and apoptosis. The aim of the present work was to examine the role of TGFbeta1 on human endometrial stromal cell apoptosis. Primary cultures of isolated stromal cells were obtained from biopsies of late secretory phase endometrium. We have found the following: (i) TGFbeta1 induced apoptosis of stromal cells in a time- and dose-dependent manner; (ii) blockade of TGFbeta1's autocrine/paracrine effect by TGFbeta1-neutralizing antibodies diminished the basal rate of stromal cell apoptosis; (iii) semi-quantitative Western blot analysis showed that TGFbeta1 caused a rapid but transient elevation of the pro-apoptotic FasL protein, without affecting the levels of Fas receptor; (iv) TGFbeta1 increased the levels of the anti-apoptotic Bcl-2 and Bcl-xL proteins, while having no significant effects on the pro-apoptotic proteins Bax and Bak, suggesting the activation of a transient survival mechanism activated in stromal cells as a parallel rescue response to the apoptosis-inducing FasL protein. In conclusion, our data provide evidence that TGFbeta1 exerts an autocrine pro-apoptotic effect on human endometrial stroma, via the FasL/Fas system.