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Molecular Human Reproduction, Vol. 9, No. 2, 91-95, February 2003
© 2003 European Society of Human Reproduction and Embryology


Article

Transforming growth factor ß1 exerts an autocrine regulatory effect on human endometrial stromal cell apoptosis, involving the FasL and Bcl-2 apoptotic pathways

Submitted on April 20, 2002; resubmitted on November 3, 2002. accepted on November 13, 2002

E. Chatzaki1, E. Kouimtzoglou1, A.N. Margioris2 and A. Gravanis1,3

Departments of 1 Pharmacology and 2 Clinical Chemistry, School of Medicine, University of Crete, Heraklion GR-711 10, Crete, Greece

3 To whom correspondence should be addressed. e-mail: gravanis{at}med.uoc.gr

Transforming growth factor ß1 (TGFß1) is expressed in human endometrium. It regulates epithelial cell proliferation and apoptosis. The aim of the present work was to examine the role of TGFß1 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) TGFß1 induced apoptosis of stromal cells in a time- and dose-dependent manner; (ii) blockade of TGFß1’s autocrine/paracrine effect by TGFß1-neutralizing antibodies diminished the basal rate of stromal cell apoptosis; (iii) semi-quantitative Western blot analysis showed that TGFß1 caused a rapid but transient elevation of the pro-apoptotic FasL protein, without affecting the levels of Fas receptor; (iv) TGFß1 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 TGFß1 exerts an autocrine pro-apoptotic effect on human endometrial stroma, via the FasL/Fas system.

Key words: apoptosis/Bcl-2/cytokines/endometrium/Fas/FasL/TGFß1


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