ENVIRONMENTAL POLLUTION
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2023
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IF 8.9
Yifan Hong,Xiazhu Zhou,Qi Li,Jing Chen,Yuexin Wei,Siyuan Wang,Xiangqin Zheng,Jie Zhao,Chengjun Yu,Jun Pei,Jie Zhang,Chunlan Long,Lianju Shen,Shengde Wu,Guanghui Wei
Di (2-ethylhexyl) phthalate (DEHP), one of phthalic acid esters, has been widely used in daily products. Its main metabolite, mono (2-ethylhexyl) phthalate (MEHP) was reported to possess higher testicular toxicity than DEHP. To explore the precise mechanism in MEHP-induced testis damage, multiple transcriptomic sequencing was employed in spermatogonia cell line GC-1 cells treated with MEHP (0, 100, and 200 μM) for 24 h. Integrative omics analysis and empirical validation revealed that Wnt signaling pathway was downregulated and wnt10a , one of hub genes, may be the key player in this process. Similar results were observed in DEHP-exposed rats. MEHP-induced disturbance of self-renewal and differentiation was dose-dependent. Moreover, self-renewal proteins were downregulated; the differentiation level was stimulated. Meanwhile, GC-1 proliferation was decreased. Stable transformation strain of wnt10a overexpression GC-1 cell line constructed from lentivirus was utilized in this study. The upregulation of Wnt10a significantly reversed the dysfunction of self-renewal and differentiation and promoted the cell proliferation. Finally, retinol, predicted to be useful in CONNECTIVITY MAP (cMAP), failed to rescue the damage caused by MEHP. Cumulatively, our findings revealed that the downregulation of Wnt10a induced the imbalance of self-renew and differentiation, and inhibition of cell proliferation in GC-1 cells after MEHP exposure.
研究领域:
毒理学
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分子生物学
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细胞生物学
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生殖生物学
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产品关联
DOI
PubMed
高影响因子
BIOLOGY BULLETIN
·
2023
·Vol. 49
·期 2
·S12
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IF 0.5
Tingting Gan,Liu Xing,Chen Xia,Shi Yichao,Wang Wenbin
Abstract Okadaic acid (OA) is a marine toxin which inhibits protein phosphatases. Its toxicities in several tissues have been well established, but the influence of exposure to low OA concentrations in male reproductive system is poorly understood. Here we aimed to explore the potential reproductive toxicity of OA and the mechanism behind it. The GC-1 cells were exposed to OA, and the changes of proliferation rates were detected. TUNEL assay was also conducted to determine the GC-1 cell apoptosis. Effects of OA on cytoskeleton and cyclin expression were investigated by fluorescein conjugated phalloidin. Potential molecular regulation on proliferation was analyzed based on transcriptomic analysis. OA inhibited the proliferation of GC-1 cells apparently with loss of cell-cell junctions and focal aggregated around the cells. The cyclin D/E mRNA and protein levels significantly decreased and the phosphorylation of ERK1/2 was blocked concordantly in OA treated cells. PPI network analysis pointed out ERK1 as a key node of responsive gene to the injury. In conclusion, OA shows apparent cytotoxicity on spermatogonial cells of male reproductive system and the cytotoxicity present was revealed by affecting the activation of ERK1/2 MAPK pathway which hinders the cyclin expression and actin stress fiber formation further.
研究领域:
毒理学
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生殖生物学
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细胞生物学
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分子生物学
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DOI
高影响因子
REPRODUCTIVE TOXICOLOGY
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2025
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IF 2.8
Cheng Cheng,Yanfan Cui,Yujie Wang,Jingfeng Huang,Jiale Ma,Tao Luo,Wen Chen
Microplastics and nanoplastics (MNPs) are widespread in the environment and have male reproductive toxicity. However, toxic interventions involving MNPs have not been extensively examined. In this investigation, we explored the elimination capacity of magnetic nano-Fe 3 O 4 on polystyrene microplastics and nanoplastics (PS-MNPs) of different sizes. This study also investigated whether magnetic nano-Fe 3 O 4 could alleviate the toxicity of PS-MNPs in spermatogonial GC-1 cells. After coprecipitation by magnetic nano-Fe 3 O 4 in ddH 2 O, the removal rates of polystyrene microplastics (PS-MPs, 4 and 10 μm) are much higher than those of PS-NPs (25 nm, 100 nm, and 500 nm). The removal rate of the PS-NPs dramatically enhanced in the salt ion solutions. In addition, 25-nm, 100-nm, 500-nm, and 4-µm PS-MNPs penetrated GC-1 cells. Nevertheless, exclusively 25-nm PS-NPs decreased cell viability, elevated reactive oxygen species, disrupted the mitochondrial membrane potential, and induced apoptosis and inflammation through the P38/MAPK and Nrf2/HO-1 signaling pathways in GC-1 cells. Interestingly, magnetic nano-Fe 3 O 4 alleviated these harmful impacts of the 25-nm PS-NPs on the GC-1 cells. In conclusion, we demonstrated the toxicity of PS-NPs in GC-1 cells and provided a viable way to alleviate their toxicity.
研究领域:
环境毒理学
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纳米技术
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生殖生物学
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材料科学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
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