Triclosan has a strong influence on the development of mouse preimplantation embryo via activating miR-134/Nanog axis
Triclosan has a strong influence on the development of mouse preimplantation embryo via activating miR-134/Nanog axis
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三氯生通过激活miR-134/Nanog轴对小鼠植入前胚胎的发育产生强烈影响
DOI：
10.1016/j.tox.2022.153349
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发表时间：
2022
期刊：
影响因子：
4.5
通讯作者：
Xiaojiao Chen
中科院分区：
文献类型：
--
作者：
Ye Yang;Danyu Ni;Wang Li;Xiaodan Shi;Xiaolan Zhang;Lin Zhou;Juan Ji;Chun Zhao;Rong Shen;Xiufeng Ling;Xiaojiao Chen
抗菌三氯生(TCS)是添加到消毒产品中的流行成分之一，在个人护理中有广泛的用途。然而，它给繁殖和发展带来了潜在的风险。不幸的是，潜在的机制在很大程度上仍然不清楚。本研究旨在研究天花粉蛋白对小鼠着床前胚胎发育的影响，并探讨其相关机制。在每个特定的发育阶段，比较对照组和实验组的发育率、多能性或干细胞标记物和microRNA(MiR)-134。长期暴露于TCS可通过阻碍桑椹胚和囊胚的形成而显著损害早期胚胎的体外发育(P<；0.05，P<；0.001)。胚胎发育受阻与多能性或干细胞标记物的表达减少有关，尤其是Nanog和Notch1。此外，基于miRWalk数据库和体外荧光素酶检测，我们证实了TCS诱导的miR-134是Nanog的负调控因子。关键是，TCS处理的受损胚胎可以通过抑制miR-134或强制过表达Nanog mRNA来挽救。总之，我们的结果强调了病理相关水平的TCS通过诱导miR-134和触发miR-134/Nanog轴来损害小鼠着床前胚胎的发育。考虑到miR-134在人和小鼠之间的高度保守性，它应该是调控植入前胚胎发育的最有前途的潜在靶点。
Antimicrobial triclosan (TCS), one of the popular ingredients added to sanitizing products, has widespread use in personal care. However, it poses potential risks to reproduction and development. Unfortunately, the underlying mechanisms remain largely unclear. This study aimed to investigate effects of TCS on the development of preimplantation mouse embryo and explore related mechanisms Mouse zygotes were collected and cultured to blastocysts in KSOM medium supplemented with four different concentrations of TCS. The development rates, pluripotency or stem cells markers, and microRNA (miR)- 134 were compared between control and experimental groups across each specific developmental stage. Prolonged exposure to TCS remarkably impaired early embryo development in vitro by hampering morula and blastocyst formations (P < 0.05, P < 0.001). The arrest of embryo development was linked with decreased expressions of pluripotency or stem cells markers, especially Nanog and Notch1. Moreover, based on miRWalk database and in vitro luciferase assays, we confirmed that miR-134 induced by TCS was a negative regulator of Nanog. Crucially, impaired TCS-treated embryos could be rescued by inhibiting miR-134 or forced overexpressing Nanog mRNA. Altogether, our results highlight that pathologically relevant level of TCS compromises preimplantation mouse embryo development by inducing miR-134 and triggering miR-134/Nanog axis. Considering high conservative of miR-134 between human and mouse, it should be the most promising potential target to regulate development of preimplantation embryo.