Yu Jun, Yang Haiming, Wang Jian, Huang Zixin, Chen Shi, Zhao Hongchang, Wang Jun, Wang Zhiyue
Jiangsu Agri-Animal Husbandry Vocational College, Taizhou, China.
College of Animal Science and Technology, Yangzhou University, Yangzhou, China.
Front Vet Sci. 2025 Jan 21;12:1527284. doi: 10.3389/fvets.2025.1527284. eCollection 2025.
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.
棉籽粕是家禽饲料中大豆粕的一种有前景的替代品，但对游离棉酚的担忧限制了其使用。尽管游离棉酚的一般毒性众所周知，但其对肝脏（其主要蓄积部位）的具体影响研究较少，尤其是在分子水平上。本研究通过形态学、转录组学和代谢组学相结合的综合分析，研究了醋酸棉酚（GA）对雏鹅的肝毒性作用。将48只体重相似的7日龄雄性雏鹅随机分为两组：对照组，接受生理盐水（0.9%，2.5 mL/kg体重）；GA处理组，以50 mg/kg体重口服GA，持续14天。组织学分析显示肝脏损伤迹象，包括颗粒变性、肝细胞肿大、坏死和线粒体损伤。转录组分析鉴定出1137个差异表达基因，其中702个上调，435个下调。关键受影响的途径包括碳代谢、糖酵解/糖异生、丙酮酸代谢、丙酸代谢、三羧酸循环、脂肪酸降解、初级胆汁酸生物合成、色氨酸代谢、半胱氨酸和蛋氨酸代谢、粘着斑和PPAR信号通路。代谢组分析显示109种差异代谢物，82种上调，27种下调，提示亚油酸代谢、花生四烯酸代谢、cAMP信号传导和血清素能突触途径受到干扰。总体而言，GA诱导的肝毒性涉及能量产生受损、脂质代谢紊乱和肝脏粘着斑异常，导致肝细胞功能障碍。这些发现突出了线粒体和关键代谢途径的脆弱性，为GA毒性的分子机制提供了见解，并指导未来减轻GA诱导的雏鹅肝脏损伤的研究。
