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Hematogenous dissemination of Chlamydia muridarum from the urethra in macrophages causes testicular infection and sperm DNA damage
Journal article   Open access   Peer reviewed

Hematogenous dissemination of Chlamydia muridarum from the urethra in macrophages causes testicular infection and sperm DNA damage

Emily R. Bryan, Avinash Kollipara, Logan K. Trim, Charles W. Armitage, Alison J. Carey, Bettina Mihalas, Kate A. Redgrove, Eileen A. McLaughlin and Kenneth W. Beagley
Biology of reproduction, v 101(4), pp 748-759
01 Oct 2019
PMID: 31373361
url
https://academic.oup.com/biolreprod/article-pdf/101/4/748/31081552/ioz146.pdfView
Published, Version of Record (VoR) Open
url
https://doi.org/10.1093/biolre/ioz146View
Published, Version of Record (VoR) Open

Abstract

Life Sciences & Biomedicine Reproductive Biology Science & Technology
The incidence of Chlamydia infection, in both females and males, is increasing worldwide. Male infections have been associated clinically with urethritis, epididymitis, and orchitis, believed to be caused by ascending infection, although the impact of infection on male fertility remains controversial. Using a mouse model of male chlamydial infection, we show that all the major testicular cell populations, germ cells, Sertoli cells, Leydig cells, and testicular macrophages can be productively infected. Furthermore, sperm isolated from vas deferens of infected mice also had increased levels of DNA damage as early as 4 weeks post-infection. Bilateral vasectomy, prior to infection, did not affect the chlamydial load recovered from testes at 2, 4, and 8 weeks post-infection, and Chlamydia-infected macrophages were detectable in blood and the testes as soon as 3 days post-infection. Partial depletion of macrophages with clodronate liposomes significantly reduced the testicular chlamydial burden, consistent with a hematogenous route of infection, with Chlamydia transported to the testes in infected macrophages. These data suggest that macrophages serve as Trojan horses, transporting Chlamydia from the penile urethra to the testes within 3 days of infection, bypassing the entire male reproductive tract. In the testes, infected macrophages likely transfer infection to Leydig, Sertoli, and germ cells, causing sperm DNA damage and impaired spermatogenesis. Summary Sentence Hematogenous dissemination of C. muridarum from the urethra in macrophages causes testicular infection and sperm DNA damage.

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Collaboration types
Domestic collaboration
Web of Science research areas
Reproductive Biology
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