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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有强烈影响。

Triclosan has a strong influence on the development of mouse preimplantation embryo via activating miR-134/Nanog axis.

机构信息

Department of Reproductive Medicine, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China.

出版信息

Toxicology. 2022 Nov;481:153349. doi: 10.1016/j.tox.2022.153349. Epub 2022 Oct 13.

Abstract

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.

摘要

三氯生(TCS)作为一种常用的消毒产品添加成分,具有广泛的个人护理用途。然而,它对生殖和发育存在潜在风险。不幸的是,其潜在机制在很大程度上仍不清楚。本研究旨在研究 TCS 对小鼠着床前胚胎发育的影响,并探讨相关机制。将小鼠受精卵收集并在 KSOM 培养基中培养至囊胚,培养基中添加了四种不同浓度的 TCS。在每个特定的发育阶段,比较对照组和实验组的胚胎发育率、多能性或干细胞标志物以及 microRNA(miR)-134。TCS 长时间暴露会显著损害体外早期胚胎发育,阻碍桑椹胚和囊胚形成(P<0.05,P<0.001)。胚胎发育停滞与多能性或干细胞标志物的表达减少有关,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 TCS 诱导的 miR-134 是 Nanog 的负调节剂。重要的是,抑制 miR-134 或强制过表达 Nanog mRNA 可挽救受损的 TCS 处理胚胎。总之,我们的研究结果表明,与疾病相关水平的 TCS 通过诱导 miR-134 并触发 miR-134/Nanog 轴来损害小鼠着床前胚胎发育。鉴于 miR-134 在人类和小鼠之间具有高度保守性,它应该是调节着床前胚胎发育最有前途的潜在靶点。

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