Identification for embryo-derived factor and its clinical application

作为我们对两步（连续）胚胎移植（ET）方法有效性的跨学科研究的结果，我们得出结论，即使在反应不良或反复失败的情况下，两步ET也是一种有效的选择。该程序可以避免取消ET，并可能使能够获得足够数量胚胎的患者受益。根据LC-MS分析，我们鉴定了胚胎衍生因子之一卵泡抑素相关基因（FLRG）蛋白，该蛋白在人子宫内膜中也有表达。在月经周期的增殖期，FLRG蛋白主要在子宫内膜上皮细胞质中检测到。在分泌期和妊娠早期，它也被检测到子宫内膜间质细胞（ESC）的细胞核。利用体外蜕膜化模型，我们证实了17β-雌二醇（E2）和孕酮（P），而不是单独的E2或P，显著诱导FLRG表达。这些结果提示，FLRG在ESC中的表达受卵巢类固醇激素的协同作用，通过蜕膜化途径进行调节，FLRG蛋白可能作为TGF-β超家族成员的结合蛋白参与了基质细胞蜕膜化的调节。

As a result of our interdisciplinary research for the effectiveness of 2-step (consecutive) embryo transfer (ET) method, we concluded that 2-step ET is an effective option even in the case of poor responder or repeated failure. This procedure can avoid cancellation of ET and may benefit patients who can obtain a sufficient number of embryos. According to the analysis of LC-Mass spectrometry, we identified one of the embryo-derived factor, follistatin related gene (FLRG) protein, which is also expressed in human endometrium. In the proliferative phase of the menstrual cycle, FLRG protein was detected predominantly in the cytoplasm of endometrial epithelium. In the secretory phase and in early pregnancy, it was also detected in the nuclei of endometrial stromal cells (ESC). Using in vitro decidualization model, we demonstrated that 17β-estradiol (E2) plus progesterone (P), but not E2 or P alone, induced FLRG expression significantly. These results suggest that FLRG expression in ESC is regulated by the concerted action of ovarian steroid hormones via decidualization and FLRG protein may participate in the regulation of stromal cell decidualization as a binding protein for the members of TGF-β superfamily.