细胞生长因子微环境与早期胚胎发育

doi:10.3969/j.issn.2095-4344.2016.11.018

摘要/Abstract

摘要：

文章快速阅读：

文题释义：

胚胎发育：是一个复杂的生理过程，提供某些细胞因子或清除微环境中有害物质等都将有助于胚胎的正常发育。通过胚胎体外培养模拟体内胚胎发育过程，可以了解众多因素对胚胎发育的影响，减少胚胎细胞凋亡。

细胞生长因子微环境：创建细胞生长因子微环境有利于胚胎发育，表皮生长因子、胰岛素样生长因子、白血病抑制因子、转化生长因子和血管内皮生长因子等生长因子在胚胎发育过程中起重要作用。

背景：哺乳动物胚胎早期发育和着床是一个非常复杂的过程，受到多种细胞因子的调节，其中表皮生长因子、转化生长因子、白血病抑制因子、胰岛素样生长因子和血管内皮生长因子在调控此过程中发挥着重要的作用。

目的：介绍影响早期胚胎发育的相关细胞因子种类、结构特点和分子调控机制，同时，对国内外关于表皮生长因子、转化生长因子、白血病抑制因子、胰岛素样生长因子和血管内皮生长因子在早期胚胎发育中的作用研究进展进行了综述。

方法：以检索词 “胚胎发育(embryos development)，表皮生长因子(Epidermal growth factor)，胰岛素样生长因子(1nsulin-like growth factor-II)，白血病抑制因子(leukemia inhibitory factor)，转化生长因子(Transforming growth factor)和血管内皮生长因子(Vascular endothelial growth factor)” 检索1989至2015年相关文献。归纳总结近几年文献报道综述5种细胞因子表皮生长因子、转化生长因子、白血病抑制因子、胰岛素样生长因子和血管内皮生长因子对于克服哺乳动物早期胚胎发育阻滞发挥的积极作用。

结果与结论：(1)细胞生长因子参与胚胎发育是研究的重点。胰岛素样生长因子能够促进胚胎的生长，表皮生长因子在胚胎发育方面表现出多种形式的功能，白血病抑制因子直接影响卵母细胞发育，孕激素可上调白血病抑制因子表达为胚胎发育提供了良好的细胞因子微环境，血管内皮生长因子促进卵母细胞的体外成熟在胚胎发育的各个阶段都起着非常重要的作用。(2)弄清这些细胞因子的调控模式，不但可以有助于胚胎的体外培养，也有助于减少胚胎凋亡，对促进胚胎发育有十分重大的意义。

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

ORCID: 0000-0002-6659-9162(王芳)

关键词: 组织构建, 组织工程, 表皮生长因子, 白细胞抑制因子, 胰岛素样生长因子, 胚胎, 细胞凋亡

Abstract:

BACKGROUND: Early mammalian embryonic development and implantation is a very complex process, which is regulated by a variety of cytokines. Moreover, epidermal growth factor, transforming growth factor, leukemia inhibitory factor, insulin-like growth factor and vascular endothelial growth factor play an important role in this regulation process.
OBJECTIVE: To introduce cytokines related to early embryonic development, including types, structural features and molecular mechanisms, and meanwhile to review the effects of epidermal growth factor, transforming growth factor, leukemia inhibitory factor, insulin-like growth factor and vascular endothelial growth factor in the early embryonic development.
METHODS: A literature retrieval was performed to search relevant articles published from 1989 to 2015 using the keywords of “embryos development, epidermal growth factor, transforming growth factor, leukemia inhibitory factor, insulin-like growth factor, vascular endothelial growth factor”. Active effects of these five kinds of cytokines in overcoming the mammalian embryonic development block were reviewed and summarized to provide theoretical and experimental basis for further optimization of the embryonic culture system in vitro.
RESULTS AND CONCLUSION: Cell growth factors involved in embryonic development is the focus of the study. Insulin-like growth factor is capable of promoting the embryonic growth; epidermal growth factor exhibits multiform functions in the embryonic development; leukemia inhibitory factor directly affects oocyte cell development, and progesterone increases the expression of leukemia inhibitory factor to provide a good cytokine microenvironment for embryonic development; vascular endothelial growth factor promotes in vitro oocyte maturation, and plays a very important role in various stages of embryonic development. To clarify these regulatory patterns of cytokines cannot only contribute to in vitro embryonic culture, but also reduce embryonic apoptosis, which is of great significance for promoting embryonic development.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

王芳, 陈绍威. 细胞生长因子微环境与早期胚胎发育[J]. 中国组织工程研究, 2016, 20(11): 1637-1643.

Wang Fang, Chen Shao-wei. Microenvironment of cell growth factors and early embryonic development[J]. Chinese Journal of Tissue Engineering Research, 2016, 20(11): 1637-1643.

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引言

人类早期胚胎发育是一个复杂的生理活动，多年来的人胚胎体外培养的研究表明，早期胚胎发育受多种细胞因子的调控^[1-4]，炎性细胞因子会抑制胚胎发育，如肿瘤坏死因子α^[5-7]，白细胞介素6^[8]，白细胞介素1及其受体等^[9]。而早期胚胎的正常发育必须依赖于源自生殖道上皮细胞的信号，抗凋亡因子和细胞生长因子形成网络发挥生物活性作用，提供某些细胞生长因子或清除微环境中有害物质等都将有助于胚胎的正常发育。因此，细胞生长因子与早期胚胎发育的关系密切，在促进早期胚胎发育、提高胚胎质量等方面具有重要意义。

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

胚胎发育受多种因素的影响，如生长因子，细胞因子，血管活性因子。近年来细胞生长因子参与胚胎发育和着床的功能研究十分热门，对其研究已深入到细胞、分子生物学水平，细胞生长因子发挥改善胚胎发育、启动胚胎着床、调节植入过程等强大作用(图1)。细胞生长因子是由正常细胞分泌的具有刺激细胞生长活性的可溶性蛋白与多肽类物质，既无药物类毒性，也无免疫反应。胚胎发育期间可合成并分泌多种肽类细胞因子包括碱性成纤维细胞生长因子、表皮生长因子、干细胞因子、胰岛素样生长因子1等^[10-13]。从目前的哺乳动物以及人类的研究资料表明，哺乳动物早期胚胎可以合成上述多肽类生长因子。这些因子通过胚胎或胚胎周围组织细胞的旁分泌或自分泌途径，促进和影响胚胎发生，同时，它们的受体也在胚胎和母体中表达，影响体外受精胚胎移植的结局。

与哺乳动物胚胎发育有关的细胞因子有胰岛素、胰岛素样生长因子家族、表皮生长因子家族、成纤维细胞生长因子家族、血小板衍生生长因子家族、白血病抑制因子、血管内皮生长因子等。胰岛素样生长因子是促合成代谢、促有丝分裂和抗细胞凋亡的因子，能调节脊椎动物细胞的生长、分化和凋亡，胰岛素样生长因子通过内分泌、自分泌或旁分泌机制在早期胚胎发育、胚胎着床中起着重要的调节作用^[14]。此外转化生长因子α是一类具有多种生物学作用、多细胞来源的细胞因子，也是表皮生长因子家族的重要成员之一。哺乳动物的胚胎、输卵管和子宫均分泌转化生长

因子α，它对胚胎的生长、发育构建有一定影响^[15]。白血病抑制因子(LIF)直接影响卵母细胞发育，经白血病抑制因子的处理过的卵母细胞类皮质颗粒迁移率增加，CD9表达提高，其表达由雌激素调节，对卵母细胞成熟和胚胎着床有重要作用。对胚胎发育有促进作用对胚胎发育有促进作用^[16-19]。血管内皮生长因子促进卵母细胞的体外成熟(IVM)，影响胚胎发育，着床，在胚胎发育的各个阶段都起着非常重要的作用^[20-22]。文章将对这些影响胚胎发育的细胞生长因子进行综述。