Ivanovsky Institute of Virology, Ministry of Health of Russian Federation, Moscow, Russia.
Int J Exp Pathol. 2014 Apr;95(2):120-30. doi: 10.1111/iep.12071. Epub 2014 Feb 23.
This study aimed to establish the influence of herpes simplex virus (HSV) on testis morphology and germ cell development using a model of ascending urogenital HSV infection in mice. Adult C57BL/6J mice were inoculated with 100 plaque-forming units of HSV1 in rete testis. Viral proteins and HSV DNA were detected from 3 days postinoculation (DPI), while capsids and virions could be visualized at 6 DPI. Infectious activity of HSV was revealed by rapid culture method in testes from 3 to 14 DPI, and virus DNA by PCR - from 3 to 100 DPI. Germ and Sertoli cells were infected during the early stages of the infection, whereas interstitial cells only occasionally contained the virus at 21 and 45 DPI. Microscopic analysis revealed severe degeneration of the germinal epithelium in the infected testes. By 21 DPI, testes became atrophic and most Sertoli cells were destroyed. No testicular regeneration and no spermatozoa in the epididymis were observed at 45 and 100 DPI. From 3 DPI, inflammatory cells accumulated in the interstitium between damaged tubules; a significant increase in the number of CD4(+), CD8(+) T lymphocytes and F4/80(+) cells was observed in the infected testes. This study shows that in the case of HSV retrograde ascent into seminiferous tubules, the acute viral infection results in irreversible atrophy of the germinal epithelium, orchitis and infertility. These results may be used to further study viral orchitis and the influence of HSV on spermatogenesis and male fertility.
本研究旨在通过建立小鼠上行泌尿生殖道单纯疱疹病毒（HSV）感染模型，研究 HSV 对睾丸形态和生精细胞发育的影响。成年 C57BL/6J 小鼠于睾丸网接种 100 噬菌斑形成单位的 HSV1。在接种后 3 天（DPI）检测病毒蛋白和 HSV DNA，在 6 DPI 可观察到衣壳和病毒颗粒。在 3 至 14 DPI 期间，通过快速培养法在睾丸中检测到 HSV 的感染活性，通过 PCR 在 3 至 100 DPI 检测到病毒 DNA。在感染早期，生殖细胞和支持细胞被感染，而间质细胞仅在 21 和 45 DPI 偶尔含有病毒。显微镜分析显示感染睾丸的生殖上皮严重退化。在 21 DPI 时，睾丸萎缩，大多数支持细胞被破坏。在 45 和 100 DPI 时，没有观察到睾丸再生和附睾中的精子。在 3 DPI 时，受损小管之间的间质中积聚了炎症细胞；在感染的睾丸中观察到 CD4(+)、CD8(+)T 淋巴细胞和 F4/80(+)细胞数量显著增加。本研究表明，在 HSV 逆行上升进入生精小管的情况下，急性病毒感染会导致生殖上皮不可逆转的萎缩、睾丸炎和不育。这些结果可用于进一步研究病毒性睾丸炎以及 HSV 对精子发生和男性生育力的影响。
