Kayisli Umit A, Selam Belgin, Guzeloglu-Kayisli Ozlem, Demir Ramazan, Arici Aydin
Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
J Immunol. 2003 Sep 1;171(5):2305-13. doi: 10.4049/jimmunol.171.5.2305.
The first known hormonal signal of the conceptus during implantation is human chorionic gonadotropin (hCG). Interestingly, increased apoptosis in human endometrium coincides with the implantation window. Factors from the fetal or placental origin as well as maternal hormonal factors are likely to have a potential role in the regulation of apoptotic signaling molecules. We hypothesized that hCG may be a placental link for the development of local maternal immunotolerance. Fas-Fas ligand (FasL) system is one of the apoptotic signaling pathways, shown to be important in the development of local immune tolerance during and after implantation. We report that hCG treatment decreases cell proliferation and increases apoptosis in endometrial cells. Moreover, hCG stimulates FasL mRNA and protein expression without affecting Fas mRNA in these cells. Interestingly, in coculture experiments, hCG-treated endometrial cells induce an increase in T cell apoptosis. Our in vivo results reveal that cells of early pregnancy decidua express strong FasL immunoreactivity, and decidual areas containing interstitial cytotrophoblasts have numerous TUNEL-positive cells. Compared with decidual areas devoid of interstitial cytotrophoblasts, we observed in decidual areas containing interstitial cytotrophoblasts clearly less amount of TUNEL-positive cells. These results suggest that hCG may be a link in the development of peritrophoblastic immune tolerance and may facilitate the trophoblast invasion by regulating proapoptotic molecules such as FasL in endometrial cells.
已知在着床期间，孕体发出的首个激素信号是人类绒毛膜促性腺激素（hCG）。有趣的是，人类子宫内膜中凋亡增加与着床窗相吻合。来自胎儿或胎盘来源的因素以及母体激素因素可能在凋亡信号分子的调节中发挥潜在作用。我们推测hCG可能是局部母体免疫耐受发展的胎盘环节。Fas-Fas配体（FasL）系统是凋亡信号通路之一，已证明其在着床期间及之后局部免疫耐受的发展中很重要。我们报告hCG处理可降低子宫内膜细胞的增殖并增加其凋亡。此外，hCG刺激这些细胞中FasL mRNA和蛋白表达，而不影响Fas mRNA。有趣的是，在共培养实验中，经hCG处理的子宫内膜细胞可诱导T细胞凋亡增加。我们的体内结果显示，早孕蜕膜细胞表达强烈的FasL免疫反应性，且含有间质细胞滋养层细胞的蜕膜区域有大量TUNEL阳性细胞。与不含间质细胞滋养层细胞的蜕膜区域相比，我们观察到含有间质细胞滋养层细胞的蜕膜区域TUNEL阳性细胞数量明显较少。这些结果表明，hCG可能是滋养层周围免疫耐受发展的一个环节，并且可能通过调节子宫内膜细胞中的促凋亡分子如FasL来促进滋养层细胞的侵袭。
