Ascending bacterial urinary tract infections can cause epididymo-orchitis. In the cauda epididymidis, this frequently leads to persistent tissue damage. Less coherent data is available concerning the functional consequences of epididymo-orchitis on testis and caput epididymidis. This in vivo study addresses the functional and spatial differences in responsiveness of murine epididymis and testis to infection with uropathogenic Escherichia coli (UPEC). Whole transcriptome analysis (WTA) was performed on testis, caput, corpus and cauda epididymidis of adult C57BL/6 J wildtype mice. Following UPEC-induced epididymo-orchitis in these mice, epididymal and testicular tissue damage was evaluated histologically and semi-quantitatively at 10 days and 31 days post-inoculation. Expression of inflammatory markers and candidate antimicrobial genes were analysed by RT-qPCR. WTA revealed distinct differences in gene signatures between caput and cauda epididymidis, particularly amonst immunity-related genes. Cellular and molecular signs of testicular inflammation and disruption of spermatogenesis were noticed at day 10, but recovery was observed by day 31. In contrast to the cauda, the caput epididymidis did not reveal any signs of gross morphological damage or presence of pro-inflammatory processes despite confirmed infection. In contrast to beta-defensins, known UPEC-associated antimicrobial peptides (AMP), like Lcn2, Camp and Lypd8, were inherently highly expressed or upregulated in the caput following infection, potentially allowing an early luminal protection from UPEC. At the time points investigated, the caput epididymidis was protected from any obvious infection/inflammation-derived tissue damage. Studies addressing earlier time-points will conclude whether in the caput epididymidis a pro-inflammatory response is indeed not essential for effective protection from UPEC.

中文翻译：

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小鼠细菌性附睾睾丸炎引起的不同组织特异性损伤。


上行细菌尿路感染可引起附睾睾丸炎。在附睾尾，这经常导致持续的组织损伤。关于附睾睾丸炎对睾丸和附睾头的功能影响的数据较少。这项体内研究探讨了小鼠附睾和睾丸对尿路致病性大肠杆菌 (UPEC) 感染的反应性的功能和空间差异。对成年 C57BL/6 J 野生型小鼠的睾丸、头、体和附睾尾进行全转录组分析 (WTA)。在这些小鼠中 UPEC 诱导的附睾睾丸炎后，在接种后 10 天和 31 天对附睾和睾丸组织损伤进行组织学和半定量评估。通过 RT-qPCR 分析炎症标志物和候选抗菌基因的表达。 WTA揭示了附睾头和附睾尾之间基因特征的明显差异，特别是与免疫相关的基因。第 10 天观察到睾丸炎症和精子发生中断的细胞和分子迹象，但到第 31 天观察到恢复。与尾部相比，附睾头没有显示任何总体形态损伤或促炎过程存在的迹象尽管确诊感染。与 β-防御素相反，已知的 UPEC 相关抗菌肽 (AMP)，如 Lcn2、Camp 和 Lypd8，在感染后的头中本质上高度表达或上调，可能允许早期的管腔保护免受 UPEC 的影响。在研究的时间点，附睾头受到保护，免受任何明显的感染/炎症引起的组织损伤。 针对早期时间点的研究将得出结论，附睾头部的促炎症反应是否确实对于有效预防 UPEC 并不重要。