Differential tissue-specific damage caused by bacterial epididymo-orchitis in the mouse

Area of Science:

• Reproductive biology
• Infectious diseases
• Immunology

Background:

• Ascending bacterial urinary tract infections can lead to epididymo-orchitis, causing persistent damage in the cauda epididymidis.
• Functional consequences of epididymo-orchitis on the testis and caput epididymidis are less understood.
• Uropathogenic Escherichia coli (UPEC) is a common cause of urinary tract infections and subsequent epididymo-orchitis.

Purpose of the Study:

• To investigate the functional and spatial differences in the response of murine epididymis and testis to UPEC infection.
• To analyze gene expression patterns and tissue damage in different regions of the male reproductive tract following infection.
• To identify potential protective mechanisms in the caput epididymidis against UPEC.

Main Methods:

• Whole transcriptome analysis (WTA) of testis, caput, corpus, and cauda epididymidis in adult C57BL/6J mice.
• Histological and semi-quantitative evaluation of tissue damage at 10 and 31 days post-inoculation.
• RT-qPCR analysis of inflammatory markers and antimicrobial genes.

Main Results:

• WTA revealed distinct gene signatures between caput and cauda epididymidis, particularly in immunity-related genes.
• Testicular inflammation and spermatogenesis disruption occurred at day 10 but showed recovery by day 31.
• The caput epididymidis showed no gross morphological damage or pro-inflammatory response despite UPEC infection, with upregulation of specific antimicrobial peptides (AMPs).

Conclusions:

• The caput epididymidis exhibits inherent protective mechanisms against UPEC, potentially through specific antimicrobial peptides, preventing infection-induced tissue damage.
• Distinct regional responses within the epididymis suggest specialized roles in managing infection.
• Further studies are needed to confirm if a pro-inflammatory response is non-essential for caput epididymidis protection against UPEC.