Hu Ting, Zhang Jiaxi, Wei Yuxuan, Zhang Lingyu, Wu Qiong
Animal Science and Technology College, Beijing University of Agriculture, Beijing, 102208, China.
Animal Science and Technology College, Beijing University of Agriculture, Beijing, 102208, China.
J Environ Manage. 2024 Nov;370:122908. doi: 10.1016/j.jenvman.2024.122908. Epub 2024 Oct 14.
Bisphenol A (BPA), a pervasive substance in our daily lives and livestock excreta, poses significant threats due to its infiltration into foods and water sources. BPA has adverse impacts on male reproductive function, particularly affecting the critical Sertoli (ST) cells that play a pivotal role in the process of spermatogonia differentiating into spermatozoa. In this study, we examined the prevalence of BPA within the pig industry and delved into the impact of BPA exposure on the motility of boar sperm, the function of pig ST cells, as well as the underlying molecular mechanisms involved. This study revealed spatial disparities in the global distribution of BPA and its analogue contamination, utilizing data compiled from 130 comprehensive studies. The average concentration of BPA found in pig feed ranges from 9.7 to 47.9 μg/kg, while in serum, it averages between 55.1 and 75.6 ng/L. The BPA concentration in feed exhibits a negative correlation with sperm viability and the percentage of progressive motile spermatozoa. Exposure to BPA reduced sperm motility in boar and ST cell activity at both 6 and 24 h. The transcriptome analysis revealed that, compared to untreated control cells, endoplasmic reticulum stress (ERS)-related genes were upregulated in ST cells exposed to BPA at 6 and 24 h. This activation of ERS in ST cells was mediated by receptor protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring protein-1α (IRE1α), and activating transcription factor 6 (ATF6). Additionally, BPA exposure triggered oxidative stress and a proinflammatory response mediated by the transcription factor NF-κB, accompanied by an increase in downstream proinflammatory cytokines. BPA exposure also led to apoptosis in ST cells and upregulated the expression levels of pro-apoptosis proteins. However, inhibiting ERS activity with 4-PBA attenuated the BPA-induced inflammatory response and apoptosis in ST cells. Our findings suggest that BPA induced apoptosis and inflammatory response in porcine ST cells through persistent activation of ERS, thereby compromising the normal function of these cells.
双酚A（BPA）是我们日常生活和家畜排泄物中普遍存在的一种物质，由于其渗入食物和水源而构成重大威胁。BPA对雄性生殖功能有不利影响，尤其会影响在精原细胞分化为精子过程中起关键作用的支持细胞（ST细胞）。在本研究中，我们调查了养猪行业中BPA的流行情况，并深入研究了BPA暴露对公猪精子活力、猪ST细胞功能以及相关潜在分子机制的影响。本研究利用从130项综合研究汇编的数据，揭示了BPA及其类似物污染在全球分布上的空间差异。猪饲料中BPA的平均浓度范围为9.7至47.9μg/kg，而血清中的平均浓度为55.1至75.6ng/L。饲料中BPA浓度与精子活力和进行性运动精子百分比呈负相关。在6小时和24小时时，暴露于BPA均会降低公猪精子活力和ST细胞活性。转录组分析显示，与未处理的对照细胞相比，在6小时和24小时暴露于BPA的ST细胞中，内质网应激（ERS）相关基因上调。ST细胞中ERS的这种激活是由受体蛋白激酶RNA样内质网激酶（PERK）、肌醇需求蛋白-1α（IRE1α）和激活转录因子6（ATF6）介导的。此外，BPA暴露引发了由转录因子NF-κB介导的氧化应激和促炎反应，同时下游促炎细胞因子增加。BPA暴露还导致ST细胞凋亡，并上调促凋亡蛋白的表达水平。然而，用4-PBA抑制ERS活性可减轻BPA诱导的ST细胞炎症反应和凋亡。我们的研究结果表明，BPA通过持续激活ERS诱导猪ST细胞凋亡和炎症反应，从而损害这些细胞的正常功能。
