Melatonin and spermidine protect early mouse embryos from ethylparaben toxicity by restoring histone modifications and subcellular structures
Ethylparaben (EtP), a widely used preservative in food and cosmetics, has raised increasing concerns in the field of reproductive toxicology due to its potential adverse effects on human health. In this study, we show that EtP exposure induces developmental arrest at the 2-cell stage in mouse embryo...
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Elsevier
2025-07-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325007845 |
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| author | Yong-feng Wang Yu-ting Wan Qing Tian Ying Yin Jia-wei Xu Li-quan Zhou |
| author_facet | Yong-feng Wang Yu-ting Wan Qing Tian Ying Yin Jia-wei Xu Li-quan Zhou |
| author_sort | Yong-feng Wang |
| collection | DOAJ |
| description | Ethylparaben (EtP), a widely used preservative in food and cosmetics, has raised increasing concerns in the field of reproductive toxicology due to its potential adverse effects on human health. In this study, we show that EtP exposure induces developmental arrest at the 2-cell stage in mouse embryos. This arrest coincides with elevated reactive oxygen species levels, mitochondrial dysfunction, DNA damage, and apoptosis. Transcriptomic analysis reveals widespread gene dysregulation following EtP exposure, characterized by the downregulation of maternal-effect genes, cleavage-stage embryo genes, and mitochondria-associated genes. These downregulated genes are primarily involved in transcription activation and apoptosis, while upregulated genes are enriched in DNA damage response pathways. Furthermore, EtP exposure alters histone modifications in embryos, leading to impaired transcriptional activity. We find that melatonin and spermidine partially rescue the developmental arrest by mitigating oxidative stress. Together, our findings demonstrate that EtP exacerbates oxidative stress, disrupts mitochondrial integrity, and damages DNA in mouse embryos, ultimately impairing transcription and developmental progression. Notably, EtP-induced disruption of histone modifications compromises zygotic genome activation, resulting in embryonic arrest. In contrast, melatonin and spermidine alleviate oxidative damage and mitochondrial dysfunction, partially restoring normal embryonic development following EtP exposure. |
| format | Article |
| id | doaj-art-b830f1c48892479eac6e149cc00d6b3a |
| institution | DOAJ |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
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| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-b830f1c48892479eac6e149cc00d6b3a2025-08-20T03:20:04ZengElsevierEcotoxicology and Environmental Safety0147-65132025-07-0130011844410.1016/j.ecoenv.2025.118444Melatonin and spermidine protect early mouse embryos from ethylparaben toxicity by restoring histone modifications and subcellular structuresYong-feng Wang0Yu-ting Wan1Qing Tian2Ying Yin3Jia-wei Xu4Li-quan Zhou5Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, ChinaInstitute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, ChinaDepartment of Gynecology and Obstetrics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, ChinaDepartment of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, ChinaNHC Key Laboratory of Birth Defects Prevention, Zhengzhou, Henan 451163, China; Corresponding author.Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China; NHC Key Laboratory of Birth Defects Prevention, Zhengzhou, Henan 451163, China; Corresponding author at: Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.Ethylparaben (EtP), a widely used preservative in food and cosmetics, has raised increasing concerns in the field of reproductive toxicology due to its potential adverse effects on human health. In this study, we show that EtP exposure induces developmental arrest at the 2-cell stage in mouse embryos. This arrest coincides with elevated reactive oxygen species levels, mitochondrial dysfunction, DNA damage, and apoptosis. Transcriptomic analysis reveals widespread gene dysregulation following EtP exposure, characterized by the downregulation of maternal-effect genes, cleavage-stage embryo genes, and mitochondria-associated genes. These downregulated genes are primarily involved in transcription activation and apoptosis, while upregulated genes are enriched in DNA damage response pathways. Furthermore, EtP exposure alters histone modifications in embryos, leading to impaired transcriptional activity. We find that melatonin and spermidine partially rescue the developmental arrest by mitigating oxidative stress. Together, our findings demonstrate that EtP exacerbates oxidative stress, disrupts mitochondrial integrity, and damages DNA in mouse embryos, ultimately impairing transcription and developmental progression. Notably, EtP-induced disruption of histone modifications compromises zygotic genome activation, resulting in embryonic arrest. In contrast, melatonin and spermidine alleviate oxidative damage and mitochondrial dysfunction, partially restoring normal embryonic development following EtP exposure.http://www.sciencedirect.com/science/article/pii/S0147651325007845EthylparabenMelatoninSpermidineZygotic genome activationPreimplantation |
| spellingShingle | Yong-feng Wang Yu-ting Wan Qing Tian Ying Yin Jia-wei Xu Li-quan Zhou Melatonin and spermidine protect early mouse embryos from ethylparaben toxicity by restoring histone modifications and subcellular structures Ecotoxicology and Environmental Safety Ethylparaben Melatonin Spermidine Zygotic genome activation Preimplantation |
| title | Melatonin and spermidine protect early mouse embryos from ethylparaben toxicity by restoring histone modifications and subcellular structures |
| title_full | Melatonin and spermidine protect early mouse embryos from ethylparaben toxicity by restoring histone modifications and subcellular structures |
| title_fullStr | Melatonin and spermidine protect early mouse embryos from ethylparaben toxicity by restoring histone modifications and subcellular structures |
| title_full_unstemmed | Melatonin and spermidine protect early mouse embryos from ethylparaben toxicity by restoring histone modifications and subcellular structures |
| title_short | Melatonin and spermidine protect early mouse embryos from ethylparaben toxicity by restoring histone modifications and subcellular structures |
| title_sort | melatonin and spermidine protect early mouse embryos from ethylparaben toxicity by restoring histone modifications and subcellular structures |
| topic | Ethylparaben Melatonin Spermidine Zygotic genome activation Preimplantation |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325007845 |
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