三氯生通过tcf12介导的RASSF8调控抑制人滋养细胞迁移。

IF 3.5 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology Pub Date : 2025-08-07 DOI:10.1016/j.fct.2025.115691

Guangzhu Dong , Wenbo Huang , Jiahe Qin , Jinzhao Ma , Yufeng Qin , Guizhen Du

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引用次数: 0

摘要

三氯生（TCS）是一种脂溶性广谱抗菌剂，广泛用于个人护理产品和医疗消毒剂中，与胚胎植入中断等不良生殖结果有关。本研究以HTR-8/SVneo细胞系为体外模型，探讨TCS暴露对滋养细胞的功能影响及其分子机制。暴露于环境相关的TCS浓度（0-100 μM）显示剂量依赖性毒性。当TCS浓度超过10 μM时，细胞活力显著降低，而当TCS浓度低于1μM时，细胞迁移能力受损。暴露于10 μM TCS的细胞的rna测序（RNA-seq）和染色质免疫沉淀测序（ChIP-seq）分析显示增强子区域的大量重新分布（以H3K27ac标记）。Motif富集分析发现TCF12是5个差异富集因子中受影响最显著的转录因子。进一步的研究表明，TCS暴露上调了TCF12及其靶基因RASSF8。通过TCF12敲低实验证实了这些因素之间的功能关系，降低了RASSF8的表达，部分逆转了tcs诱导的迁移抑制。荧光素酶报告基因检测证实TCF12与RASSF8启动子区域直接结合。本研究揭示了一种新的TCF12-RASSF8信号通路介导tcs诱导的滋养细胞迁移障碍，为这种常见抗菌药物的生殖毒性提供了分子见解，并确定了tcs诱导的生殖并发症的潜在干预靶点。

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Triclosan inhibits human trophoblast cell migration via TCF12-mediated RASSF8 regulation

Triclosan (TCS), a fat-soluble broad-spectrum antimicrobial agent widely used in personal care products and medical disinfectants, has been linked to adverse reproductive outcomes including disrupted embryo implantation. The aim of the present study was to investigate the functional consequences and molecular mechanisms of TCS exposure on trophoblast cells, using the HTR-8/SVneo cell line as an established in vitro model of human extravillous trophoblasts. Exposure to environmentally relevant TCS concentrations (0–100 μM) revealed dose-dependent toxicity. Cell viability significantly decreased at more than 10 μM TCS, while migration was impaired at concentrations as low as 1 μM. RNA-sequencing (RNA-seq) and Chromatin immunoprecipitation sequencing (ChIP-seq) analyses of cells exposed to 10 μM TCS showed substantial redistribution of enhancer regions (marked by H3K27ac). Motif enrichment analysis identified TCF12 as the most significantly affected transcription factor among five differentially enriched factors. Further investigation demonstrated that TCS exposure upregulated both TCF12 and its target gene RASSF8. The functional relationship between these factors was confirmed through TCF12 knockdown experiments, which decreased RASSF8 expression and partially reversed TCS-induced migration inhibition. Luciferase reporter assays verified direct binding of TCF12 to the RASSF8 promoter region. This study reveals a novel TCF12-RASSF8 signaling pathway mediating TCS-induced trophoblast migration impairment, providing molecular insights into the reproductive toxicity of this common antimicrobial agent and identifying potential intervention targets for TCS-induced reproductive complications.

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来源期刊

Food and Chemical Toxicology 工程技术-毒理学

CiteScore

10.90

自引率

4.70%

发文量

651

审稿时长

31 days

期刊介绍： Food and Chemical Toxicology (FCT), an internationally renowned journal, that publishes original research articles and reviews on toxic effects, in animals and humans, of natural or synthetic chemicals occurring in the human environment with particular emphasis on food, drugs, and chemicals, including agricultural and industrial safety, and consumer product safety. Areas such as safety evaluation of novel foods and ingredients, biotechnologically-derived products, and nanomaterials are included in the scope of the journal. FCT also encourages submission of papers on inter-relationships between nutrition and toxicology and on in vitro techniques, particularly those fostering the 3 Rs. The principal aim of the journal is to publish high impact, scholarly work and to serve as a multidisciplinary forum for research in toxicology. Papers submitted will be judged on the basis of scientific originality and contribution to the field, quality and subject matter. Studies should address at least one of the following: -Adverse physiological/biochemical, or pathological changes induced by specific defined substances -New techniques for assessing potential toxicity, including molecular biology -Mechanisms underlying toxic phenomena -Toxicological examinations of specific chemicals or consumer products, both those showing adverse effects and those demonstrating safety, that meet current standards of scientific acceptability. Authors must clearly and briefly identify what novel toxic effect (s) or toxic mechanism (s) of the chemical are being reported and what their significance is in the abstract. Furthermore, sufficient doses should be included in order to provide information on NOAEL/LOAEL values.