双酚 A (BPA) 是一种普遍存在的环境污染物，可通过诱导氧化应激对人类和动物免疫系统产生有害影响。硒（Se）缺乏会损害免疫器官组织，并对环境污染物的毒性表现出协同作用。然而，BPA与低硒联合引起的氧化应激、细胞凋亡和自噬在家禽免疫器官法氏囊中的研究尚未见报道。因此，本研究建立BPA和/或低硒肉鸡模型和鸡淋巴瘤细胞（MDCC-MSB-1细胞）模型，探讨BPA和/或低硒对家禽法氏囊的影响。数据显示，BPA和/或低硒破坏了法氏囊的正常结构，BPA（60μM）显着降低MDCC-MSB-1细胞的活性并破坏正常形态（IC50=192.5±1.026μM）。与对照组相比，BPA组和低硒组细胞凋亡和自噬增加，活性氧（ROS）的产生增加。这抑制了 AKT/FOXO1 通路，导致线粒体融合/分裂失衡（Mfn1、Mfn2、OPA1 增加，DRP1 减少）和功能障碍（CI-NDUFB8、CII-SDHB、CIII-UQCRC2、CIV-MTCO1、CV-ATP5A1 ，ATP）。此外，BPA和低硒的联合暴露加剧了上述变化。 N-乙酰半胱氨酸 (NAC) 治疗可降低 ROS 水平并激活 AKT/FOXO1 通路，进一步减轻 BPA 和低硒诱导的细胞凋亡和自噬。 3-甲基腺嘌呤（3-MA，自噬抑制剂）治疗后，低硒 BPA 诱导的细胞凋亡加剧。总之，这些结果表明，BPA 和低硒通过调节 ROS/AKT/FOXO1 通路，加剧鸡法氏囊的细胞凋亡和自噬。版权所有 © 2023。由 Elsevier B.V. 出版。

Bisphenol A (BPA) is a ubiquitous environmental pollutant that can have harmful effects on human and animal immune systems by inducing oxidative stress. Selenium (Se) deficiency damages immune organ tissues and exhibits synergistic effects on the toxicity of environmental pollutants. However, oxidative stress, cell apoptosis, and autophagy caused by the combination of BPA and low-Se, have not been studied in the bursa of Fabricius of the immune organ of poultry. Therefore, in this study, BPA and/or low-Se broiler models and chicken lymphoma cells (MDCC-MSB-1 cells) models were established to investigate the effects of BPA and/or low-Se on the bursa of Fabricius of poultry. The data showed that BPA and/or low-Se disrupted the normal structure of the bursa of Fabricius, BPA (60 μM) significantly reduced the activity of MDCC-MSB-1 cells and disrupted normal morphology (IC50 = 192.5 ± 1.026 μM). Compared with the Control group, apoptosis and autophagy were increased in the BPA or low-Se groups, and the generation of reactive oxygen species (ROS) was increased. This inhibited the AKT/FOXO1 pathway, leading to mitochondrial fusion/division imbalance (Mfn1, Mfn2, OPA1 were increased, DRP1 was decreased) and dysfunction (CI-NDUFB8, CII-SDHB, CIII-UQCRC2, CIV-MTCO1, CV-ATP5A1, ATP). Furthermore, combined exposure of BPA and low-Se aggravated the above-mentioned changes. Treatment with N-acetylcysteine (NAC) reduced ROS levels and activated the AKT/FOXO1 pathway to further alleviate BPA and low-Se-induced apoptosis and autophagy. Apoptosis induced by low-Se + BPA was exacerbated after 3-Methyladenine (3-MA, autophagy inhibitor) treatment. Together, these results indicated that BPA and low-Se aggravated apoptosis and autophagy of the bursa of Fabricius in chickens by regulating the ROS/AKT/FOXO1 pathway.Copyright © 2023. Published by Elsevier B.V.