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白细胞介素-1β诱导小鼠着床前胚胎自噬并提高囊胚质量。

Interleukin-1 beta induces autophagy of mouse preimplantation embryos and improves blastocyst quality.

机构信息

College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, Gansu, China.

Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Research Institute of Fish Culture and Hydrobiology, University of South Bohemia in České Budějovice, Vodňany, Czech Republic.

出版信息

J Cell Biochem. 2020 Feb;121(2):1087-1100. doi: 10.1002/jcb.29345. Epub 2019 Aug 27.

DOI:10.1002/jcb.29345
PMID:31453635
Abstract

Autophagy is one of the basic cellular mechanism during preimplantation development of mammalian embryos, and it plays crucial role in several physiological processes. It is induced by interleukin (IL)-1β in mammalian cells. Our present study shows that IL-1β is important for autophagy activation in embryo development. Our in vitro culture system analysis shows effect of IL-1β in medium on the development of mouse embryos and it was found to be concentration dependent. A preimplantation embryo culture using medium containing IL-1β did not improve cleavage and blastocyst development rates of mouse embryos; however, blastocyst quality was significantly improved by increasing total cell number, especially in supplementary 20 ng/mL IL-1β. Furthermore, autophagy activation mainly occurs in 2 to 4 cell embryo and blastocyst, 20 ng/mL IL-1β into culture medium can effectively enhance levels of messenger RNA and protein of autophagy-related-factors in 2 to 4 cell embryos and blastocyst, while these factors reduce in VGX-1027 (IL-1β inhibitor) groups that also reduce the quality of blastocyst. Effects of IL-1β on the development of embryo reduced in 20 ng/mL IL-1β supplemented group when 5 mM 3-methyladenine (3-MA) was also added, which used to inhibit autophagy activation in endogenous PtdIns3Ks signal pathway. Our current results show that exogenous IL-1β can effectively induce autophagy in mouse embryos at stages of 2 to 8 cell and blastocyst, that also help to improve the quality of blastocyst.

摘要

自噬是哺乳动物胚胎植入前发育过程中的一种基本细胞机制,它在几个生理过程中起着至关重要的作用。它是由白细胞介素 (IL)-1β在哺乳动物细胞中诱导的。我们目前的研究表明,IL-1β在胚胎发育中对自噬的激活很重要。我们的体外培养系统分析表明,IL-1β在培养基中的作用对小鼠胚胎的发育有影响,且这种作用呈浓度依赖性。使用含有 IL-1β 的培养基进行的胚胎前体培养并不能提高小鼠胚胎的卵裂和囊胚发育率;然而,通过增加总细胞数,特别是在补充 20ng/mL IL-1β 的情况下,囊胚质量得到了显著改善。此外,自噬激活主要发生在 2 到 4 细胞胚胎和囊胚中,20ng/mL IL-1β进入培养基可以有效地增强 2 到 4 细胞胚胎和囊胚中自噬相关因子的信使 RNA 和蛋白水平,而在 VGX-1027(IL-1β抑制剂)组中,这些因子减少,囊胚质量也降低。当在 20ng/mL IL-1β 补充组中也添加 5mM 3-甲基腺嘌呤 (3-MA) 时,IL-1β对胚胎发育的影响会减少,3-MA 用于抑制内源性 PtdIns3Ks 信号通路中的自噬激活。我们目前的结果表明,外源性 IL-1β可以有效地诱导 2 到 8 细胞期和囊胚期的小鼠胚胎发生自噬,这也有助于提高囊胚的质量。

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