mTOR通路抑制剂对卵丘扩展与体外受精的影响

Study on mTOR inhibitors to cumulus expansion and in vitro fertilization

目的研究哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)通路抑制剂对卵丘及卵母细胞发育潜能的影响。方法收集小鼠较大有腔卵泡中卵丘-卵母细胞复合体(cumulusoocyte complexes,COCs)作为体外培养的研究对象,在培养液中加入不同浓度的mTOR通路抑制剂(雷帕霉素、Torin1),分析mTOR通路抑制剂对卵丘及卵母细胞发育潜能的影响。结果雷帕霉素、Torin1可以有效抑制COCs中mTOR信号通路,Torin1有明显影响卵丘细胞扩展的作用,使卵母细胞受精及着床前胚胎发育潜能下降。结论 mTOR信号通路抑制剂有明显降低卵母细胞质量的效应,是维持COCs活性及促进卵丘和卵母细胞的发育潜能所必需。

Objective To investigate the influence of mammalian target of rapamycin（mTOR） inhibitors on cumulus cells and oocyte. Method Collected cumulus-oocyte complexes（COCs） of large follicles in mice ovaries for in vitro culture, by added different concentrations of mTOR inhibitors in culture medium, analyzed its influence on cumulus cells and oocyte. Result Rapamycin, Torin1 could effectively inhibit the transmission of mTOR signaling pathway in COCs, and the ability of COCs cultured with Torin1 to undergo cumulus expansion and the competence of oocyte for fertilization and supporting preimplantation development were dramatically compromised. Conclusion mTOR inhibitors can significantly decrease oocyte quality, and it indicates that mTOR signal pathway is necessary to maintain COCs activity and its developmental competence.