College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.
Key Laboratory of Animal Diseases and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China.
Virulence. 2024 Dec;15(1):2384564. doi: 10.1080/21505594.2024.2384564. Epub 2024 Jul 29.
Porcine reproductive and respiratory syndrome virus (PRRSV) causes a highly contagious disease that threatens the global swine industry. Recent studies have focused on the damage that PRRSV causes to the reproductive system of male pigs, although pathological research is lacking. Therefore, we examined the pathogenic mechanisms in male piglets infected with PRRSV. Gross and histopathological changes indicated that PRRSV affected the entire reproductive system, as confirmed via immunohistochemical analysis. PRRSV infected Sertoli cells and spermatogonia. To test the new hypothesis that PRRSV infection in piglets impairs blood - testis barrier (BTB) development, we investigated the pathology of PRRSV damage in the BTB. PRRSV infection significantly decreased the quantity and proliferative capacity of Sertoli cells constituting the BTB. Zonula occludens-1 and β-catenin were downregulated in cell - cell junctions. Transcriptome analysis revealed that several crucial genes and signalling pathways involved in the growth and development of Leydig cells, Sertoli cells, and tight junctions in the testes were downregulated. Apoptosis, necroptosis, inflammatory, and oxidative stress-related pathways were activated, whereas hormone secretion-related pathways were inhibited. Many Sertoli cells and spermatogonia underwent apoptosis during early differentiation. Infected piglets exhibited disrupted androgen secretion, leading to significantly reduced testosterone and anti-Müllerian hormone levels. A cytokine storm occurred, notably upregulating cytokines such as tumour necrosis factor-α and interleukin-6. Markers of oxidative-stress damage (i.e. HO, malondialdehyde, and glutathione) were upregulated, whereas antioxidant-enzyme activities (i.e. superoxide dismutase, total antioxidant capacity, and catalase) were downregulated. Our results demonstrated that PRRSV infected multiple organs in the male reproductive system, which impaired growth in the BTB.
猪繁殖与呼吸综合征病毒 (PRRSV) 引起一种高度传染性疾病，威胁着全球养猪业。最近的研究集中在 PRRSV 对雄性猪生殖系统的损害上，尽管缺乏病理学研究。因此，我们研究了感染 PRRSV 的雄性仔猪的发病机制。大体和组织病理学变化表明，PRRSV 影响了整个生殖系统，免疫组化分析也证实了这一点。PRRSV 感染了支持细胞和精原细胞。为了验证 PRRSV 感染仔猪会损害血睾屏障 (BTB) 的新假设，我们研究了 BTB 中 PRRSV 损伤的病理学。PRRSV 感染显著降低了构成 BTB 的支持细胞的数量和增殖能力。细胞 - 细胞连接处的紧密连接蛋白 - 1 和 β-连环蛋白下调。转录组分析显示，睾丸中涉及间质细胞、支持细胞和紧密连接生长和发育的几个关键基因和信号通路下调。凋亡、坏死性凋亡、炎症和氧化应激相关途径被激活，而激素分泌相关途径受到抑制。许多支持细胞和精原细胞在早期分化过程中发生凋亡。感染仔猪表现出雄激素分泌紊乱，导致睾酮和抗缪勒管激素水平显著降低。发生了细胞因子风暴，显著上调了肿瘤坏死因子-α和白细胞介素-6 等细胞因子。氧化应激损伤标志物（如 HO、丙二醛和谷胱甘肽）上调，而抗氧化酶活性（如超氧化物歧化酶、总抗氧化能力和过氧化氢酶）下调。我们的研究结果表明，PRRSV 感染了雄性生殖系统的多个器官，损害了 BTB 的生长。
