Ye Ting, Yang Ruiquan, He Shumao, Li Jiahui, Liu Yi, Li Can, Luo Heng
State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Medical University, Guiyang, 550014, People's Republic of China.
Natural Products Research Center of Guizhou Province, Guiyang, 550014, Guizhou, People's Republic of China.
Sci Rep. 2025 Mar 28;15(1):10752. doi: 10.1038/s41598-025-94902-5.
The study investigates the synergistic endocrine disruption and cellular toxicity resulting from co-exposure to polyethylene microplastics (PE-MPs) and bisphenol A (BPA) in zebrafish and MLTC-1 cells. Previous research has extensively examined the individual effects of PE-MPs and BPA on endocrine systems and cellular health. However, the specific interactions and combined toxicological impacts of these two common environmental pollutants remain underexplored, particularly in terms of their synergistic effects on endocrine pathways and cellular viability. To fill this knowledge gap, we characterized PE-MPs using scanning electron microscopy and Raman spectrometry and exposed MLTC-1 cells to PE-MPs, BPA, or combinations of both. The results showed that co-exposure to 100 µg/mL PE-MPs and 100-150 µmol/L BPA for 48 h significantly decreased cell viability, increased apoptosis rates, induced G2/M cell cycle arrest, reduced mitochondrial membrane potential, and altered the transcriptional expression of genes related to steroidogenesis. Specifically, co-exposure upregulated the Ar while downregulating Lhr and 3β-Hsd, with these effects being more pronounced than those observed with single exposures. In a complementary in vivo study, adult zebrafish were exposed to environmentally relevant concentrations of PE-MPs (1 mg/L) and BPA (1.5 µg/L) for 28 days. This co-exposure resulted in significant increases in the GSI and alterations in the gene expression associated with the HPG axis. In male zebrafish brains, genes such as Gnrh2, Esr1, and Ar were downregulated, while in female brains, Gnrh3, Esr1, and Ar also exhibited downregulation. In male testes, Star, Cyp11a1, and Hsd11b2 were upregulated, whereas Cyp19a1a, Hsd3b, Hsd20b, and Hsd17b3 were downregulated. In contrast, female ovaries showed upregulation of Cyp11a1, Cyp17, Cyp11b, Hsd3b, Hsd20b, and Hsd17b3, while Cyp19a1a was downregulated, indicating a sex-specific endocrine disruption. Overall, the findings reveal that co-exposure to PE-MPs and BPA induces synergistic toxic effects both in vitro and in vivo, which underscores the importance of studying the effects of combined pollutants to better assess environmental health risks.
该研究调查了斑马鱼和MLTC - 1细胞共同暴露于聚乙烯微塑料（PE - MPs）和双酚A（BPA）时产生的协同内分泌干扰和细胞毒性。先前的研究广泛考察了PE - MPs和BPA对内分泌系统和细胞健康的单独影响。然而，这两种常见环境污染物的具体相互作用和联合毒理学影响仍未得到充分研究，特别是在它们对内分泌途径和细胞活力的协同作用方面。为了填补这一知识空白，我们使用扫描电子显微镜和拉曼光谱对PE - MPs进行了表征，并将MLTC - 1细胞暴露于PE - MPs、BPA或两者的组合中。结果表明，共同暴露于100μg/mL的PE - MPs和100 - 150μmol/L的BPA 48小时显著降低了细胞活力，增加了凋亡率，诱导了G2/M期细胞周期阻滞，降低了线粒体膜电位，并改变了与类固醇生成相关基因的转录表达。具体而言，共同暴露上调了Ar，而下调了Lhr和3β - Hsd，这些影响比单一暴露时更明显。在一项补充的体内研究中，成年斑马鱼暴露于环境相关浓度的PE - MPs（1mg/L）和BPA（1.5μg/L）中28天。这种共同暴露导致GSI显著增加以及与HPG轴相关的基因表达发生改变。在雄性斑马鱼大脑中，Gnrh2、Esr1和Ar等基因被下调，而在雌性大脑中，Gnrh3、Esr1和Ar也表现出下调。在雄性睾丸中，Star、Cyp11a1和Hsd11b2被上调，而Cyp19a1a、Hsd3b、Hsd20b和Hsd17b3被下调。相反，雌性卵巢中Cyp11a1、Cyp17、Cyp11b、Hsd3b、Hsd20b和Hsd17b3被上调，而Cyp19a1a被下调，表明存在性别特异性的内分泌干扰。总体而言，研究结果表明，共同暴露于PE - MPs和BPA在体外和体内均诱导了协同毒性作用，这凸显了研究混合污染物影响以更好地评估环境健康风险的重要性。
