Effects of an environmental chemical mixture on early-stage embryo development: In vitro evidence from human embryonic stem cells

IF 2.6 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro Pub Date : 2025-06-12 DOI:10.1016/j.tiv.2025.106101

Bai Li , Yihang Kevin Pan , Xiaolei Jin , Hing Man Chan

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引用次数: 0

Abstract

Environmental chemicals are known risk factors for adverse pregnancy outcomes. However, the effects of environmentally relevant concentrations of chemical mixtures are less studied. This study investigated the effects of a mixture containing 23 chemicals reported in blood samples of Nunavik pregnant women, termed the Nunavik Chemical Mixture (NCM), on embryo development using human embryonic stem cells (hESCs). hESCs were exposed to 0-100X of NCM (X is the sum of geometric mean concentrations of NCM's components) for 24 h and 6 d Cell viability, apoptosis, stress response, cell cycle, cytoskeleton, autophagy, and expression of lineage marker genes/proteins were measured after exposures. NCM decreased cell viability and adhesion, induced apoptosis, disrupted the cell cycle, and altered the expression of cytoskeleton, autophagy proteins, and lineage marker genes/proteins in a dose-dependent manner. These results suggested that NCM affected embryo development, leading to potential adverse pregnancy outcomes if it occurs in vivo. Moreover, the effects caused by NCM were different from those caused by the same doses of MeHg alone that we previously found, indicating potential interactions among components within the mixture. Our results highlight the importance of considering the potential combined effects of chemical mixtures when assessing health risks in populations exposed to various environmental chemicals.

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环境化学混合物对早期胚胎发育的影响：来自人类胚胎干细胞的体外证据。

众所周知，环境化学物质是导致不良妊娠结果的危险因素。然而，对与环境有关的化学混合物浓度的影响的研究较少。这项研究调查了努纳维克孕妇血液样本中含有23种化学物质的混合物，称为努纳维克化学混合物（NCM），对人类胚胎干细胞（hESCs）胚胎发育的影响。将hESCs暴露于0-100倍的NCM （X为NCM各组分几何平均浓度之和）中24 h和6 d后，检测细胞活力、凋亡、应激反应、细胞周期、细胞骨架、自噬和谱系标记基因/蛋白的表达。NCM降低细胞活力和粘附，诱导细胞凋亡，破坏细胞周期，并以剂量依赖的方式改变细胞骨架、自噬蛋白和谱系标记基因/蛋白的表达。这些结果表明，NCM影响胚胎发育，如果发生在体内，可能会导致潜在的不良妊娠结局。此外，NCM引起的影响与我们之前发现的相同剂量的MeHg单独引起的影响不同，这表明混合物中成分之间可能存在相互作用。我们的研究结果强调了在评估暴露于各种环境化学品的人群的健康风险时，考虑化学混合物的潜在综合影响的重要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Toxicology in Vitro 医学-毒理学

CiteScore

6.50

自引率

3.10%

发文量

181

审稿时长

65 days

期刊介绍： Toxicology in Vitro publishes original research papers and reviews on the application and use of in vitro systems for assessing or predicting the toxic effects of chemicals and elucidating their mechanisms of action. These in vitro techniques include utilizing cell or tissue cultures, isolated cells, tissue slices, subcellular fractions, transgenic cell cultures, and cells from transgenic organisms, as well as in silico modelling. The Journal will focus on investigations that involve the development and validation of new in vitro methods, e.g. for prediction of toxic effects based on traditional and in silico modelling; on the use of methods in high-throughput toxicology and pharmacology; elucidation of mechanisms of toxic action; the application of genomics, transcriptomics and proteomics in toxicology, as well as on comparative studies that characterise the relationship between in vitro and in vivo findings. The Journal strongly encourages the submission of manuscripts that focus on the development of in vitro methods, their practical applications and regulatory use (e.g. in the areas of food components cosmetics, pharmaceuticals, pesticides, and industrial chemicals). Toxicology in Vitro discourages papers that record reporting on toxicological effects from materials, such as plant extracts or herbal medicines, that have not been chemically characterized.