Selam B, Kayisli U A, Mulayim N, Arici A
Yale University School of Medicine, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, New Haven, Connecticut 06520-8063, USA.
Biol Reprod. 2001 Oct;65(4):979-85. doi: 10.1095/biolreprod65.4.979.
Implantation involves a complex set of events, including apoptosis in endometrial cells. Apoptosis in human endometrium coincides with the implantation window, suggesting a potential role for steroid hormones in its regulation. 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 hypothesized that FasL expression in human endometrium is cycle-dependent and that sex steroid hormones regulate FasL expression. We first studied menstrual cycle-dependent expression of FasL in human endometrium by immunohistochemistry in 24 samples. We then investigated the in vitro regulation of FasL expression by ovarian steroid hormones. Throughout the menstrual cycle immunohistochemical 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 endometrial stromal and glandular cells. Strong FasL expression was observed throughout the late-proliferative and secretory phases. Semiquantitative reverse transcription-polymerase chain reaction analysis in cultured endometrial glandular cells demonstrated that estradiol and progesterone stimulate FasL mRNA expression. Western blot analysis in endometrial glandular and stromal cells in culture revealed that estradiol alone and in combination with progesterone up-regulated FasL protein expression. These results suggest that estradiol and progesterone may have a role in the regulation of maternal immunotolerance for the implantation of a semiallograft embryo by inducing FasL expression. We speculate that increased FasL expression may mediate the apoptosis of endometrial cells and thus may play a role in trophoblast invasion.
着床涉及一系列复杂的事件，包括子宫内膜细胞的凋亡。人类子宫内膜的凋亡与着床窗同步，提示甾体激素在其调节中可能发挥作用。Fas配体（FasL）是分化细胞和胚胎发育中凋亡的介质之一。FasL与其受体Fas相互作用，通过自分泌和旁分泌信号诱导凋亡。我们假设人类子宫内膜中FasL的表达是周期依赖性的，并且性甾体激素调节FasL的表达。我们首先通过免疫组织化学研究了24个样本中人类子宫内膜中FasL的月经周期依赖性表达。然后我们研究了卵巢甾体激素对FasL表达的体外调节。在整个月经周期中，子宫内膜功能层的免疫组织化学染色强度比基底层更强。在子宫内膜基质细胞和腺细胞中，FasL免疫反应性在增殖中期和后期逐渐增加。在增殖后期和分泌期均观察到强烈的FasL表达。培养的子宫内膜腺细胞中的半定量逆转录-聚合酶链反应分析表明，雌二醇和孕酮刺激FasL mRNA表达。培养的子宫内膜腺细胞和基质细胞中的蛋白质免疫印迹分析显示，单独的雌二醇以及与孕酮联合使用均上调了FasL蛋白表达。这些结果表明，雌二醇和孕酮可能通过诱导FasL表达在调节母体对半同种异体移植胚胎着床的免疫耐受中发挥作用。我们推测FasL表达增加可能介导子宫内膜细胞的凋亡，因此可能在滋养层侵袭中发挥作用。
