Comprehensive analysis of histophysiology, transcriptomics and metabolomics in goslings exposed to gossypol acetate: unraveling hepatotoxic mechanisms
Cottonseed meal is a promising alternative to soybean meal in poultry feed, but concerns over free gossypol limit its use. Although the general toxicity of free gossypol is well-known, its specific effects on the liver—the primary site where it accumulates—are less thoroughly studied, particularly a...
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| Format: | Article |
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Veterinary Science |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fvets.2025.1527284/full |
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| author | Jun Yu Jun Yu Haiming Yang Jian Wang Zixin Huang Shi Chen Hongchang Zhao Jun Wang Zhiyue Wang |
| author_facet | Jun Yu Jun Yu Haiming Yang Jian Wang Zixin Huang Shi Chen Hongchang Zhao Jun Wang Zhiyue Wang |
| author_sort | Jun Yu |
| collection | DOAJ |
| description | Cottonseed meal is a promising alternative to soybean meal in poultry feed, but concerns over free gossypol limit its use. Although the general toxicity of free gossypol is well-known, its specific effects on the liver—the primary site where it accumulates—are less thoroughly studied, particularly at the molecular level. This study investigated the hepatotoxic effects of gossypol acetate (GA) on goslings through a comprehensive analysis combining morphology, transcriptomics, and metabolomics. Forty-eight 7-day-old male goslings with similar body weight (BW) were randomly assigned to two groups: a control group, receiving a saline solution (0.9%, 2.5 mL/kg BW), and a GA-treated group, administered GA at 50 mg/kg BW orally for 14 days. Histological analysis revealed signs of liver damage, including granular degeneration, hepatocyte enlargement, necrosis, and mitochondrial injury. Transcriptomic analysis identified 1,137 differentially expressed genes, with 702 upregulated and 435 downregulated. Key affected pathways included carbon metabolism, glycolysis/gluconeogenesis, pyruvate metabolism, propanoate metabolism, TCA cycle, fatty acid degradation, primary bile acid biosynthesis, tryptophan metabolism, cysteine and methionine metabolism, focal adhesion, and the PPAR signaling pathway. Metabolomic analysis revealed 109 differential metabolites, 82 upregulated and 27 downregulated, implicating disruptions in linoleic acid metabolism, arachidonic acid metabolism, cAMP signaling, and serotonergic synapse pathways. Overall, GA-induced hepatotoxicity involves impaired energy production, disrupted lipid metabolism, and abnormal liver focal adhesion, leading to liver cell dysfunction. These findings highlight the vulnerability of mitochondria and critical metabolic pathways, providing insights into the molecular mechanisms of GA toxicity and guiding future studies on mitigating GA-induced liver damage in goslings. |
| format | Article |
| id | doaj-art-d8dc10eff6ae4762a7096e31fcc5cb5b |
| institution | Kabale University |
| issn | 2297-1769 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Veterinary Science |
| spelling | doaj-art-d8dc10eff6ae4762a7096e31fcc5cb5b2025-01-21T14:17:16ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692025-01-011210.3389/fvets.2025.15272841527284Comprehensive analysis of histophysiology, transcriptomics and metabolomics in goslings exposed to gossypol acetate: unraveling hepatotoxic mechanismsJun Yu0Jun Yu1Haiming Yang2Jian Wang3Zixin Huang4Shi Chen5Hongchang Zhao6Jun Wang7Zhiyue Wang8Jiangsu Agri-Animal Husbandry Vocational College, Taizhou, ChinaCollege of Animal Science and Technology, Yangzhou University, Yangzhou, ChinaCollege of Animal Science and Technology, Yangzhou University, Yangzhou, ChinaJiangsu Agri-Animal Husbandry Vocational College, Taizhou, ChinaCollege of Animal Science and Technology, Yangzhou University, Yangzhou, ChinaCollege of Animal Science and Technology, Yangzhou University, Yangzhou, ChinaJiangsu Agri-Animal Husbandry Vocational College, Taizhou, ChinaJiangsu Agri-Animal Husbandry Vocational College, Taizhou, ChinaCollege of Animal Science and Technology, Yangzhou University, Yangzhou, ChinaCottonseed meal is a promising alternative to soybean meal in poultry feed, but concerns over free gossypol limit its use. Although the general toxicity of free gossypol is well-known, its specific effects on the liver—the primary site where it accumulates—are less thoroughly studied, particularly at the molecular level. This study investigated the hepatotoxic effects of gossypol acetate (GA) on goslings through a comprehensive analysis combining morphology, transcriptomics, and metabolomics. Forty-eight 7-day-old male goslings with similar body weight (BW) were randomly assigned to two groups: a control group, receiving a saline solution (0.9%, 2.5 mL/kg BW), and a GA-treated group, administered GA at 50 mg/kg BW orally for 14 days. Histological analysis revealed signs of liver damage, including granular degeneration, hepatocyte enlargement, necrosis, and mitochondrial injury. Transcriptomic analysis identified 1,137 differentially expressed genes, with 702 upregulated and 435 downregulated. Key affected pathways included carbon metabolism, glycolysis/gluconeogenesis, pyruvate metabolism, propanoate metabolism, TCA cycle, fatty acid degradation, primary bile acid biosynthesis, tryptophan metabolism, cysteine and methionine metabolism, focal adhesion, and the PPAR signaling pathway. Metabolomic analysis revealed 109 differential metabolites, 82 upregulated and 27 downregulated, implicating disruptions in linoleic acid metabolism, arachidonic acid metabolism, cAMP signaling, and serotonergic synapse pathways. Overall, GA-induced hepatotoxicity involves impaired energy production, disrupted lipid metabolism, and abnormal liver focal adhesion, leading to liver cell dysfunction. These findings highlight the vulnerability of mitochondria and critical metabolic pathways, providing insights into the molecular mechanisms of GA toxicity and guiding future studies on mitigating GA-induced liver damage in goslings.https://www.frontiersin.org/articles/10.3389/fvets.2025.1527284/fullhepatotoxicgossypol acetategoosetranscriptomicsmetabolomics |
| spellingShingle | Jun Yu Jun Yu Haiming Yang Jian Wang Zixin Huang Shi Chen Hongchang Zhao Jun Wang Zhiyue Wang Comprehensive analysis of histophysiology, transcriptomics and metabolomics in goslings exposed to gossypol acetate: unraveling hepatotoxic mechanisms Frontiers in Veterinary Science hepatotoxic gossypol acetate goose transcriptomics metabolomics |
| title | Comprehensive analysis of histophysiology, transcriptomics and metabolomics in goslings exposed to gossypol acetate: unraveling hepatotoxic mechanisms |
| title_full | Comprehensive analysis of histophysiology, transcriptomics and metabolomics in goslings exposed to gossypol acetate: unraveling hepatotoxic mechanisms |
| title_fullStr | Comprehensive analysis of histophysiology, transcriptomics and metabolomics in goslings exposed to gossypol acetate: unraveling hepatotoxic mechanisms |
| title_full_unstemmed | Comprehensive analysis of histophysiology, transcriptomics and metabolomics in goslings exposed to gossypol acetate: unraveling hepatotoxic mechanisms |
| title_short | Comprehensive analysis of histophysiology, transcriptomics and metabolomics in goslings exposed to gossypol acetate: unraveling hepatotoxic mechanisms |
| title_sort | comprehensive analysis of histophysiology transcriptomics and metabolomics in goslings exposed to gossypol acetate unraveling hepatotoxic mechanisms |
| topic | hepatotoxic gossypol acetate goose transcriptomics metabolomics |
| url | https://www.frontiersin.org/articles/10.3389/fvets.2025.1527284/full |
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