3-methyl-4-nitrophenol disturbs the maternal-to-zygotic transition of early embryos by damaging mitochondrial function and histone modification
3-methyl-4-nitrophenol (PNMC), a chemical prevalent in various industries for drug, dye, and leather production, also serves as a primary byproduct of organophosphate insecticides. Despite its global recognition as an endocrine disruptor with documented reproductive toxicity, its detrimental impact...
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Elsevier
2025-01-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651324016713 |
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| author | Fan Chen An-Feng Luo Kai-Xin Pan Hao Gu Chang-Fan Zhou Wei Zeng Song Liu Adrian Molenaar Hong-Yan Ren Li-Jun Huo Yan-Zhen Bi |
| author_facet | Fan Chen An-Feng Luo Kai-Xin Pan Hao Gu Chang-Fan Zhou Wei Zeng Song Liu Adrian Molenaar Hong-Yan Ren Li-Jun Huo Yan-Zhen Bi |
| author_sort | Fan Chen |
| collection | DOAJ |
| description | 3-methyl-4-nitrophenol (PNMC), a chemical prevalent in various industries for drug, dye, and leather production, also serves as a primary byproduct of organophosphate insecticides. Despite its global recognition as an endocrine disruptor with documented reproductive toxicity, its detrimental impact on preimplantation embryonic development has yet to be thoroughly investigated. In this study, through the in vitro culture of mice embryos, it was initially observed that even low concentrations of PNMC exposure led to a significant reduction in blastocyst formation and a sharp decline in the ratio of inner cell mass within the blastocysts. SMART-seq2 transcriptome sequencing further confirmed that PNMC treatment disrupted global gene expression in 2-cell embryos, with differentially expressed genes enriched in multiple signaling pathways, including those related to autophagy, apoptosis, fertilization, embryonic development, transcription, and mRNA processing. Integration of transcriptome data with open databases revealed that both zygotic genome activation genes and maternal factors experienced significant transcript-level disruptions. Moreover, the study demonstrated that these gene expression changes were closely associated with mitochondrial dysfunction, evidenced by diminished mitochondrial membrane potential, reduced ATP production, aberrant expression of mitochondria-related genes, increased ROS accumulation, and heightened DNA damage in PNMC-treated embryos. Additionally, PNMC exposure induced defects in histone modification, as shown by altered levels of H3K9me3 and H3K27me3, H3K9ac and H3K27ac. Lastly, the findings indicated that PNMC triggered apoptosis in embryos, validated by elevated BAX and CASPASE3 expression, alongside positive TUNEL staining. In summary, PNMC exposure impairs the maternal-to-zygotic transition, likely through mitochondrial dysfunction and histone modification, culminating in developmental arrest and apoptosis in mouse preimplantation embryos. |
| format | Article |
| id | doaj-art-692198200ea4454fbdf338dad923326e |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-692198200ea4454fbdf338dad923326e2025-01-23T05:25:52ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-012891175953-methyl-4-nitrophenol disturbs the maternal-to-zygotic transition of early embryos by damaging mitochondrial function and histone modificationFan Chen0An-Feng Luo1Kai-Xin Pan2Hao Gu3Chang-Fan Zhou4Wei Zeng5Song Liu6Adrian Molenaar7Hong-Yan Ren8Li-Jun Huo9Yan-Zhen Bi10Key Laboratory of Animal Embryo Engineering and Molecular Breeding of Hubei Province, Institute of Animal Sciences and Veterinary Medicine, Hubei Academy of Agricultural Sciences, Wuhan 430070, ChinaKey Laboratory of Animal Embryo Engineering and Molecular Breeding of Hubei Province, Institute of Animal Sciences and Veterinary Medicine, Hubei Academy of Agricultural Sciences, Wuhan 430070, ChinaKey Laboratory of Animal Embryo Engineering and Molecular Breeding of Hubei Province, Institute of Animal Sciences and Veterinary Medicine, Hubei Academy of Agricultural Sciences, Wuhan 430070, ChinaKey Laboratory of Animal Embryo Engineering and Molecular Breeding of Hubei Province, Institute of Animal Sciences and Veterinary Medicine, Hubei Academy of Agricultural Sciences, Wuhan 430070, ChinaKey Laboratory of Animal Embryo Engineering and Molecular Breeding of Hubei Province, Institute of Animal Sciences and Veterinary Medicine, Hubei Academy of Agricultural Sciences, Wuhan 430070, ChinaKey Laboratory of Animal Embryo Engineering and Molecular Breeding of Hubei Province, Institute of Animal Sciences and Veterinary Medicine, Hubei Academy of Agricultural Sciences, Wuhan 430070, ChinaKey Laboratory of Animal Embryo Engineering and Molecular Breeding of Hubei Province, Institute of Animal Sciences and Veterinary Medicine, Hubei Academy of Agricultural Sciences, Wuhan 430070, ChinaKey Laboratory of Animal Embryo Engineering and Molecular Breeding of Hubei Province, Institute of Animal Sciences and Veterinary Medicine, Hubei Academy of Agricultural Sciences, Wuhan 430070, China; Rumen Microbiology and Animal Nutrition and Physiology AgResearch, Grasslands Campus, Fitzherbert Research Centre, Palmerston North 4410, New ZealandKey Laboratory of Animal Embryo Engineering and Molecular Breeding of Hubei Province, Institute of Animal Sciences and Veterinary Medicine, Hubei Academy of Agricultural Sciences, Wuhan 430070, ChinaKey Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Education Ministry of China, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, ChinaKey Laboratory of Animal Embryo Engineering and Molecular Breeding of Hubei Province, Institute of Animal Sciences and Veterinary Medicine, Hubei Academy of Agricultural Sciences, Wuhan 430070, China; Hubei Hongshan Laboratory, Wuhan 430070, China; Corresponding author at: Key Laboratory of Animal Embryo Engineering and Molecular Breeding of Hubei Province, Institute of Animal Sciences and Veterinary Medicine, Hubei Academy of Agricultural Sciences, Wuhan 430070, China.3-methyl-4-nitrophenol (PNMC), a chemical prevalent in various industries for drug, dye, and leather production, also serves as a primary byproduct of organophosphate insecticides. Despite its global recognition as an endocrine disruptor with documented reproductive toxicity, its detrimental impact on preimplantation embryonic development has yet to be thoroughly investigated. In this study, through the in vitro culture of mice embryos, it was initially observed that even low concentrations of PNMC exposure led to a significant reduction in blastocyst formation and a sharp decline in the ratio of inner cell mass within the blastocysts. SMART-seq2 transcriptome sequencing further confirmed that PNMC treatment disrupted global gene expression in 2-cell embryos, with differentially expressed genes enriched in multiple signaling pathways, including those related to autophagy, apoptosis, fertilization, embryonic development, transcription, and mRNA processing. Integration of transcriptome data with open databases revealed that both zygotic genome activation genes and maternal factors experienced significant transcript-level disruptions. Moreover, the study demonstrated that these gene expression changes were closely associated with mitochondrial dysfunction, evidenced by diminished mitochondrial membrane potential, reduced ATP production, aberrant expression of mitochondria-related genes, increased ROS accumulation, and heightened DNA damage in PNMC-treated embryos. Additionally, PNMC exposure induced defects in histone modification, as shown by altered levels of H3K9me3 and H3K27me3, H3K9ac and H3K27ac. Lastly, the findings indicated that PNMC triggered apoptosis in embryos, validated by elevated BAX and CASPASE3 expression, alongside positive TUNEL staining. In summary, PNMC exposure impairs the maternal-to-zygotic transition, likely through mitochondrial dysfunction and histone modification, culminating in developmental arrest and apoptosis in mouse preimplantation embryos.http://www.sciencedirect.com/science/article/pii/S0147651324016713PNMCEarly embryonic developmentMaternal-to-zygotic transitionZygotic genome activationMitochondriaHistone modification |
| spellingShingle | Fan Chen An-Feng Luo Kai-Xin Pan Hao Gu Chang-Fan Zhou Wei Zeng Song Liu Adrian Molenaar Hong-Yan Ren Li-Jun Huo Yan-Zhen Bi 3-methyl-4-nitrophenol disturbs the maternal-to-zygotic transition of early embryos by damaging mitochondrial function and histone modification Ecotoxicology and Environmental Safety PNMC Early embryonic development Maternal-to-zygotic transition Zygotic genome activation Mitochondria Histone modification |
| title | 3-methyl-4-nitrophenol disturbs the maternal-to-zygotic transition of early embryos by damaging mitochondrial function and histone modification |
| title_full | 3-methyl-4-nitrophenol disturbs the maternal-to-zygotic transition of early embryos by damaging mitochondrial function and histone modification |
| title_fullStr | 3-methyl-4-nitrophenol disturbs the maternal-to-zygotic transition of early embryos by damaging mitochondrial function and histone modification |
| title_full_unstemmed | 3-methyl-4-nitrophenol disturbs the maternal-to-zygotic transition of early embryos by damaging mitochondrial function and histone modification |
| title_short | 3-methyl-4-nitrophenol disturbs the maternal-to-zygotic transition of early embryos by damaging mitochondrial function and histone modification |
| title_sort | 3 methyl 4 nitrophenol disturbs the maternal to zygotic transition of early embryos by damaging mitochondrial function and histone modification |
| topic | PNMC Early embryonic development Maternal-to-zygotic transition Zygotic genome activation Mitochondria Histone modification |
| url | http://www.sciencedirect.com/science/article/pii/S0147651324016713 |
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