Tang Yujun, Li Hao, Zeng Yutian, Yang Cuiting, Zhang Run, Lund Arab Khan, Zhang Ming
College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China.
Faculty of Animal Production and Technology, Shaheed Benazir Bhutto University of Veterinary and Animal Science, Sakrand 67210, Pakistan.
Int J Mol Sci. 2025 Mar 19;26(6):2753. doi: 10.3390/ijms26062753.
Viral infections of the reproductive tract and testis in male yaks, often resulting from natural mating under grazing conditions, can lead to infertility due to Leydig cell (LC) apoptosis, immune activation, oxidative stress, and reduced testosterone production. Spermidine (SPD), a potential therapeutic agent with antioxidant and anti-aging properties, might alleviate oxidant stress, immune response, and virus infection caused by apoptosis. In this study, firstly testicular Leydig cells of yak were induced with Poly(I:C), the pathogen-associated molecular pattern of the dsRNA virus, as a pathogenic model at the cellular level. Secondly, immune response, apoptosis, oxidative stress, and testosterone synthesis were measured in LC with or without SPD culture medium. Finally, transcriptomic sequencing was utilized to investigate the molecular mechanisms underlying the protective effects of SPD. These results suggested Poly(I:C) damaged the function of Leydig cells, significantly decreased the concentration of testosterone, and induced immune response, oxidative stress, and cell apoptosis, while SPD significantly alleviated the immune response and oxidative stress, and then significantly inhibited cell apoptosis and restores testosterone production in LCs. Transcriptomic analysis revealed that SPD significantly alleviates inflammation and apoptosis induced by Poly(I:C), reducing immune response and cellular damage through the regulation of several key gene expressions. These findings suggest SPD has the potential ability to mitigate Poly(I:C)-induced immune response, oxidative stress, and apoptosis, and then restore testosterone production in Leydig cells, offering a promising strategy to protect and enhance male yak fertility after infection with dsRNA virus.
雄性牦牛生殖道和睾丸的病毒感染通常是在放牧条件下自然交配所致，可因睾丸间质细胞（LC）凋亡、免疫激活、氧化应激以及睾酮分泌减少而导致不育。亚精胺（SPD）是一种具有抗氧化和抗衰老特性的潜在治疗剂，可能会减轻由凋亡引起的氧化应激、免疫反应和病毒感染。在本研究中，首先用双链RNA病毒的病原体相关分子模式聚肌胞苷酸（Poly(I:C)）诱导牦牛睾丸间质细胞，作为细胞水平的致病模型。其次，在有或无SPD培养基的情况下，检测间质细胞中的免疫反应、凋亡、氧化应激和睾酮合成。最后，利用转录组测序研究SPD保护作用的分子机制。这些结果表明，Poly(I:C)损害了间质细胞的功能，显著降低了睾酮浓度，并诱导了免疫反应、氧化应激和细胞凋亡，而SPD显著减轻了免疫反应和氧化应激，进而显著抑制细胞凋亡并恢复间质细胞中的睾酮分泌。转录组分析显示，SPD显著减轻了Poly(I:C)诱导的炎症和凋亡，通过调节几个关键基因的表达减少免疫反应和细胞损伤。这些发现表明，SPD具有减轻Poly(I:C)诱导的免疫反应、氧化应激和凋亡，进而恢复间质细胞睾酮分泌的潜在能力，为保护和提高感染双链RNA病毒后的雄性牦牛生育能力提供了一种有前景的策略。
