猪繁殖与呼吸综合征病毒下调circ-107191/miR-34c/RAD54L轴,通过受损的同源重组修复促进睾丸细胞凋亡

IF 2.5 2区 农林科学 Q3 REPRODUCTIVE BIOLOGY
Bingzhou Huang , Dong You , Baoling Liu , Siyuan Lai , Yanru Ai , Jianbo Huang , Yuancheng Zhou , Liangpeng Ge , Xiu Zeng , Zhiwen Xu , Ling Zhu
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引用次数: 0

摘要

猪繁殖与呼吸综合征病毒(PRRSV)感染损害了男性生殖功能,造成了巨大的经济损失。本研究通过转录组学分析研究prrsv诱导的睾丸功能障碍,鉴定出463个circrna、50个mirna和4627个mrna在感染睾丸中差异表达。功能富集分析强调了circRNA-miRNA-mRNA网络在免疫应答、细胞凋亡和生殖细胞维持中的作用。circ-107191/miR-34c/RAD54L轴作为关键途径出现:PRRSV感染降低circ-107191,从而增强miR-34c活性,抑制RAD54L表达,从而加剧细胞凋亡和氧化应激。离体猪睾丸模型表明,circ-107191的降低或miR-34c水平的升高会破坏血睾丸屏障的完整性,增加炎症和细胞凋亡,并抑制睾酮的产生。恢复circ-107191表达或抑制miR-34c可减轻组织损伤,增强细胞增殖,减少氧化应激,稳定内分泌功能。这些发现强调circ-107191/miR-34c/RAD54L轴是prrsv诱导的男性不育症的潜在治疗靶点,为ncrna介导的生殖调控提供了新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Porcine reproductive and respiratory syndrome virus downregulates the circ-107191/miR-34c/RAD54L axis to promote testicular cell apoptosis via impaired homologous recombination repair
Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) infection impairs male reproductive function, causing substantial economic losses. This study investigates PRRSV-induced testicular dysfunction through transcriptomic analysis, identifying 463 circRNAs, 50 miRNAs, and 4627 mRNAs that are differentially expressed in infected testes. Functional enrichment analysis underscores the role of the circRNA-miRNA-mRNA network in immune responses, apoptosis, and germ cell maintenance. The circ-107191/miR-34c/RAD54L axis emerges as a pivotal pathway: PRRSV infection reduces circ-107191, which enhances miR-34c activity and suppresses RAD54L expression, thereby exacerbating apoptosis and oxidative stress. Ex vivo porcine testicular models demonstrate that decreased circ-107191 or elevated miR-34c levels disrupt blood-testis barrier integrity, increase inflammation and apoptosis, and suppress testosterone production. Restoring circ-107191 expression or inhibiting miR-34c mitigates tissue damage, enhances cell proliferation, reduces oxidative stress, and stabilizes endocrine function. These findings highlight the circ-107191/miR-34c/RAD54L axis as a potential therapeutic target for PRRSV-induced male infertility, providing novel insights into ncRNA-mediated reproductive regulation.
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来源期刊
Theriogenology
Theriogenology 农林科学-生殖生物学
CiteScore
5.50
自引率
14.30%
发文量
387
审稿时长
72 days
期刊介绍: Theriogenology provides an international forum for researchers, clinicians, and industry professionals in animal reproductive biology. This acclaimed journal publishes articles on a wide range of topics in reproductive and developmental biology, of domestic mammal, avian, and aquatic species as well as wild species which are the object of veterinary care in research or conservation programs.
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