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DNA damage contributes to transcriptional and immunological dysregulation of testicular cells during Chlamydia infection

Journal Article


Abstract


  • Chlamydia is the most commonly reported sexually transmitted bacterial infection, with 127 million notifications worldwide each year. Both males and females are susceptible to the pathological impacts on fertility that Chlamydia infections can induce. However, male chlamydial infections, particularly within the upper reproductive tract, including the testis, are not well characterized. In this study, using mouse testicular cell lines, we examined the impact of infection on testicular cell lineage transcriptomes and potential mechanisms for this impact. The somatic cell lineages exhibited significantly fragmented genomes during infection. Likely resulting from this, each of the Leydig, Sertoli and germ cell lineages experienced extensive transcriptional dysregulation, leading to significant changes in cellular biological pathways, including interferon and germ-Sertoli cell signalling. The cell lineages, as well as isolated spermatozoa from infected mice, also contained globally hypomethylated DNA. Cumulatively, the DNA damage and epigenetic-mediated transcriptional dysregulation observed within testicular cells during chlamydial infection could result in the production of spermatozoa with abnormal epigenomes, resulting in previously observed subfertility in infected animals and congenital defects in their offspring.

Publication Date


  • 2021

Citation


  • Bryan, E. R., Barrero, R. A., Cheung, E., Tickner, J. A. D., Trim, L. K., Richard, D., . . . Carey, A. J. (2021). DNA damage contributes to transcriptional and immunological dysregulation of testicular cells during Chlamydia infection. American Journal of Reproductive Immunology, 86(1). doi:10.1111/aji.13400

Scopus Eid


  • 2-s2.0-85101171470

Volume


  • 86

Issue


  • 1

Abstract


  • Chlamydia is the most commonly reported sexually transmitted bacterial infection, with 127 million notifications worldwide each year. Both males and females are susceptible to the pathological impacts on fertility that Chlamydia infections can induce. However, male chlamydial infections, particularly within the upper reproductive tract, including the testis, are not well characterized. In this study, using mouse testicular cell lines, we examined the impact of infection on testicular cell lineage transcriptomes and potential mechanisms for this impact. The somatic cell lineages exhibited significantly fragmented genomes during infection. Likely resulting from this, each of the Leydig, Sertoli and germ cell lineages experienced extensive transcriptional dysregulation, leading to significant changes in cellular biological pathways, including interferon and germ-Sertoli cell signalling. The cell lineages, as well as isolated spermatozoa from infected mice, also contained globally hypomethylated DNA. Cumulatively, the DNA damage and epigenetic-mediated transcriptional dysregulation observed within testicular cells during chlamydial infection could result in the production of spermatozoa with abnormal epigenomes, resulting in previously observed subfertility in infected animals and congenital defects in their offspring.

Publication Date


  • 2021

Citation


  • Bryan, E. R., Barrero, R. A., Cheung, E., Tickner, J. A. D., Trim, L. K., Richard, D., . . . Carey, A. J. (2021). DNA damage contributes to transcriptional and immunological dysregulation of testicular cells during Chlamydia infection. American Journal of Reproductive Immunology, 86(1). doi:10.1111/aji.13400

Scopus Eid


  • 2-s2.0-85101171470

Volume


  • 86

Issue


  • 1