Chlamydia trachomatis is the most prevalent sexually transmitted pathogen with over 100 million new cases of infection detected annually worldwide, and is a major cause of reproductive morbidity and infertility in both males and females. The association of chlamydial infection with pelvic inflammatory disease and tubal factor infertility in females is well established. However, the effects of chlamydia infection on ovarian function and folliculogenesis have never been investigated.
Using our established mouse model of C. muridarum infection, we harvested ovaries 6 and 30 days post vaginal inoculation and localised chlamydial major outer membrane protein (MOMP) by immunohistochemistry (IHC), evaluated follicular development using stereology, and assessed expression of chlamydial-specific genes, steroidogenic enzymes, Toll-like receptor signalling components and cytokines by qRT-PCR. Ovaries from infected and naïve mice were compared.
Localisation of MOMP by IHC confirmed that mouse ovaries were infected with chlamydia bacterium 6 days post-inoculation and expressed significant levels of chlamydia-specific genes, 16S and ompA, indicating that the infection was transcriptionally active. Levels of cytokines (TNF, IL10, IL6 and IFNγ) were significantly elevated 6 days post-inoculation, but returned to normal 30 days post-inoculation, indicating that an acute inflammatory response was initiated and resolved. However, transcriptionally inactive chlamydial inclusion bodies were still detected within the ovary at 30 days. Steroidogenic enzyme expression (CYP11) was reduced, and corpora lutea persistence declined. Populations of secondary follicles were significantly reduced 6 days post-inoculation, indicating damage to follicular development in the presence of an active infection. These data indicated that a persistent form of infection developed 30 days post-inoculation. These findings are significant because persistent infections are not detectible by current methods of clinical testing, and may reactivate causing continued damage in the ovary, thus posing a substantial threat to sexual health and fertility.