Regulation of Fas ligand expression by estradiol and progesterone in humanendometrium

Implantation involves a complex set of events, including apoptosis in endom etrial cells. Apoptosis in human endometrium coincides with the implantatio n window, suggesting a potential role for steroid hormones in its regulatio n. Fas ligand (FasL) is one of the mediators of apoptosis in differentiated cells and in embryonic development. Interaction of FasL with its receptor, Fas, induces apoptosis through autocrine and paracrine signaling. We hypot hesized that FasL expression in human endometrium is cycle-dependent and th at sex steroid hormones regulate FasL expression. We first studied menstrua l cycle-dependent expression of FasL in human endometrium by immunohistoche mistry in 24 samples. We then investigated the in vitro regulation of FasL expression by ovarian steroid hormones. Throughout the menstrual cycle immu nohistochemical staining intensity was stronger in the functional layer of endometrium than it was in the basal layer. FasL immunoreactivity increased gradually through the mid- and late-proliferative phases in both endometri al stromal and glandular cells. Strong FasL expression was observed through out the late-proliferative and secretory phases. Semiquantitative reverse t ranscription-polymerase chain reaction analysis in cultured endometrial gla ndular cells demonstrated that estradiol and progesterone stimulate FasL mR NA expression. Western blot analysis in endometrial glandular and stromal c ells in culture revealed that estradiol alone and in combination with proge sterone up-regulated FasL protein expression. These results suggest that es tradiol and progesterone may have a role in the regulation of maternal immu notolerance for the implantation of a semiallograft embryo by inducing FasL expression. We speculate that increased FasL expression may mediate the ap optosis of endometrial cells and thus may play a role in trophoblast invasi on.