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Updated: Sep 12, 2025
In Vitro Assays to Evaluate the Migration, Invasion, and Proliferation of Immortalized Human First-trimester Trophoblast Cell Lines
Published on: March 5, 2019
Triclosan inhibits human trophoblast cell migration via TCF12-mediated RASSF8 regulation
Guangzhu Dong1, Wenbo Huang2, Jiahe Qin2
1Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China; Baijiahu Community Health Service Center, Moling Street, Jiangning District, Nanjing, 211102, China.
Abstract:
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.
Insights
Triclosan (TCS) exposure harms trophoblast cell migration by disrupting the TCF12-RASSF8 pathway. This finding offers insights into TCS reproductive toxicity and potential interventions for related complications.
Area of Science:
- Reproductive toxicology
- Cellular and molecular biology
- Environmental health
Background:
- Triclosan (TCS), a common antimicrobial, is linked to adverse reproductive outcomes.
- TCS is widely used in personal care products and medical disinfectants.
- Its effects on human trophoblast cells and underlying mechanisms require elucidation.
Purpose of the Study:
- Investigate the functional effects of TCS on trophoblast cells.
- Elucidate the molecular mechanisms behind TCS-induced reproductive toxicity.
- Identify potential therapeutic targets for TCS-related reproductive issues.
Main Methods:
- Utilized HTR-8/SVneo cells as a model for human extravillous trophoblasts.
- Applied RNA-sequencing (RNA-seq) and ChIP-sequencing (ChIP-seq) to analyze gene expression and epigenetic changes.
- Conducted TCF12 knockdown and luciferase reporter assays to confirm molecular interactions.
Main Results:
- TCS exposure caused dose-dependent toxicity and impaired trophoblast cell migration.
- Significant redistribution of enhancer regions (H3K27ac) and altered transcription factor activity (TCF12) were observed.
- TCS upregulated TCF12 and its target gene RASSF8, with TCF12 directly binding to the RASSF8 promoter.
Conclusions:
- Identified a novel TCF12-RASSF8 signaling pathway mediating TCS-induced trophoblast migration impairment.
- Provided molecular insights into the reproductive toxicity of Triclosan.
- Highlighted potential intervention targets for TCS-induced reproductive complications.
