Identification for embryo-derived factor and its clinical application

胚胎源性因子的鉴定及其临床应用

• 批准号: 14571556
• 负责人: NODA Yoichi
• 金额: $ 1.86万
• 依托单位: Shiga University of Medical Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571556/
• 关键词: enbryo-trophicfactor; 2step embryo transfer; In Vitro Fertilization-Embryo Transfer

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.

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，即使在反应不佳或反复失败的情况下，两步胚胎移植也是一个有效的选择。该方法可避免取消胚胎移植，并可使获得足够数量胚胎的患者受益。根据LC-MS分析，我们鉴定了一种胚源性因子，即卵泡抑素相关基因(Folistatin Related gene，FLRG)蛋白，该蛋白也在人的子宫内膜中表达。在月经周期增生期，FLRG蛋白主要定位于子宫内膜上皮细胞质。在分泌期和妊娠早期，子宫内膜间质细胞(ESC)的细胞核中也有表达。在体外蜕膜化模型中，17β-雌二醇(E_2)和孕酮(P)联用能显著诱导FRG的表达，但不能单独作用于E_2或P。这些结果提示，FRG在胚胎干细胞中的表达受卵巢类固醇激素通过蜕膜化的协同作用而调节，FRG蛋白可能作为转化生长因子-β超家族成员的结合蛋白参与基质细胞蜕膜化的调节。

项目成果

Hirose M, Murata A, Kita N, Aotani H, Takebayashi K, Noda Y: "Successful intrauterine treatment with radiofrequency ablation in a case of acardiac twin pregnancy complicated with a hydropic pump twin."Ultrasound Obstet Gynecol. Vol.23. 509-512 (2004)

Hirose M、Murata A、Kita N、Aotani H、Takebayashi K、Noda Y：“在无心双胎妊娠合并水肿泵双胞胎的情况下，通过射频消融成功进行宫内治疗。”超声妇产科。

後藤 栄: "月経開始から卵巣刺激開始までの期間の長短が体外受精・胚移植の成績に及ぼす影響についての検討"SHIGA MEDICAL JOURNAL. 25. 51-54 (2003)

Sakae Goto：“从月经开始到卵巢刺激开始的时间长度对体外受精和胚胎移植结果的影响的研究”滋贺医学杂志 25. 51-54 (2003)。

王華芹: "FLRG (follistatin-related gene) expression in human endometrium."Journal of Clinical Endocrinology and Metabolism. 86. 1281-1286 (2003)

王华琪：“FLRG（卵泡抑素相关基因）在人子宫内膜中的表达。”临床内分泌与代谢杂志86。1281-1286（2003）。

Hirose M, Kimura F, Wang HQ, Takebayashi K, Kobayashi M, Nakanishi K, Akiyama M, Kimura T, Noda Y: "Protein S gene mutation in a young woman with type III protein S deficiency and venous thrombosis during pregnancy."J Thromb Thrombolysis. Vol.13, No.2. 85

Hirose M、Kimura F、Wang HQ、Takebayashi K、Kobayashi M、Nakanishi K、Akiyama M、Kimura T、Noda Y：“妊娠期间患有 III 型蛋白 S 缺乏和静脉血栓的年轻女性的蛋白 S 基因突变。”J

後藤 栄: "当科における不育症症例の取り扱いと治療成績の検討"産婦人科治療. 86巻. 875-879 (2003)

后藤荣：“我科不孕症的处理及治疗结果的检查”妇产科治疗第86卷875-879（2003）。