Actin Disorganization Plays a Vital Role in Impaired Embryonic Development of In Vitro-Produced Mouse Preimplantation Embryos.
Actin Disorganization Plays a Vital Role in Impaired Embryonic Development of In Vitro-Produced Mouse Preimplantation Embryos.
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肌动蛋白紊乱在体外产生的小鼠植入前胚胎的胚胎发育受损中起着至关重要的作用
DOI：
10.1371/journal.pone.0130382
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Tian JH
中科院分区：
文献类型：
--
作者：
Tan K;An L;Wang SM;Wang XD;Zhang ZN;Miao K;Sui LL;He SZ;Nie JZ;Wu ZH;Tian JH
辅助生殖技术(ART)正被越来越多地应用于克服不孕不育。然而，作为抗逆转录病毒治疗的主要程序，体外生产过程可能会导致胚胎发育异常和后代出现健康相关问题。了解ART引起的副作用的潜在机制对于改进ART过程非常重要。在这项研究中，我们对体内(IVO)和体外产生(IVP)的小鼠囊胚进行了转录组谱的比较。我们的结果提示，肌动蛋白组织的异常可能是IVP胚胎发育障碍的一个主要因素。为了验证这一点，我们研究了肌动蛋白解体对IVP植入前胚胎发育的影响。细胞松弛素B(CB)对肌动蛋白组织的特异性破坏表明，良好组织的肌动蛋白对体外胚胎发育是必不可少的。在培养液中加入10-9M的褪黑素，显著逆转了与肌动蛋白组织相关的基因的表达模式，包括Arhgef2、Bcl2、Coro2b、Flnc和Palld。免疫荧光分析表明，褪黑素处理IVP胚胎后，从8-细胞期开始，肌动蛋白细丝(F-肌动蛋白)的分布和组织明显改善。更重要的是，我们发现褪黑素减轻了CB介导的F-肌动蛋白的异常分布和组织，并挽救了CB诱导的胚胎发育受损。这是首次研究表明肌动蛋白的解体与IVP胚胎植入前阶段的发育受损有关。我们还证明，改善肌动蛋白组织是优化现有IVP系统的一个有前途的策略。
Assisted reproductive technology (ART) is being increasingly applied to overcome infertility. However, the in vitro production process, the main procedure of ART, can lead to aberrant embryonic development and health-related problems in offspring. Understanding the mechanisms underlying the ART-induced side effects is important to improve the ART process. In this study, we carried out comparative transcriptome profiling between in vivo- (IVO) and in vitro- produced (IVP) mouse blastocysts. Our results suggested that aberrant actin organization might be a major factor contributing to the impaired development of IVP embryos. To test this, we examined the effect of actin disorganization on the development of IVP preimplantation embryos. Specific disruption of actin organization by cytochalasin B (CB) indicated that well-organized actin is essential for in vitro embryonic development. Supplementing the culture medium with 10–9 M melatonin, a cytoskeletal modulator in adult somatic cells, significantly reversed the disrupted expression patterns of genes related to actin organization, including Arhgef2, Bcl2, Coro2b, Flnc, and Palld. Immunofluorescence analysis showed that melatonin treatment of IVP embryos significantly improved the distribution and organization of actin filaments (F-actin) from the 8-cell stage onwards. More importantly, we found that melatonin alleviated the CB-mediated aberrant F-actin distribution and organization and rescued CB-induced impaired embryonic development. This is the first study to indicate that actin disorganization is implicated in impaired development of IVP embryos during the preimplantation stage. We also demonstrated that improving actin organization is a promising strategy to optimize existing IVP systems.
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影响因子：
16.2
作者：
Lanier, LM;Gates, MA;Gertler, FB
通讯作者：
Gertler, FB
影响因子：
4.4
作者：
Driver AM;Peñagaricano F;Huang W;Ahmad KR;Hackbart KS;Wiltbank MC;Khatib H
通讯作者：
Khatib H
影响因子：
2.2
作者：
Abecia, JA;Forcada, F;Zúñiga, O
通讯作者：
Zúñiga, O
影响因子：
6.1
作者：
Duan, Xing;Dai, Xiao-Xin;Sun, Shao-Chen
通讯作者：
Sun, Shao-Chen
影响因子：
6.1
作者：
Biggers, JD;McGinnis, LK;Lawitts, JA
通讯作者：
Lawitts, JA