Chronic Oral Inflammation Impairs Female Reproduction in a Murine Model

Abstract

Chronic inflammation, including in the oral cavity, is known to affect the activity of multiple systems and organs, including the reproductive system. However, the mechanism of this effect, including how the inflammatory signal is propagated from the oral cavity to the ovary, is unknown. To decipher this mechanism, we used an animal model of inflammation associated with dental implants. Our aim was to test the effect of dental implants on female fertility and oocyte quality and to explore the mechanisms that mediate the effect of chronic inflammation on female fertility. In our model, female mice underwent tooth extraction, followed by titanium implant insertion. Four weeks after implant insertion, the local immunity and systemic immune response and fertility and oocyte quality were assessed by flow cytometry, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, immunofluorescence, and hematoxylin and eosin staining of ovary sections. Our results show that implant placement led to an increased inflammatory response in the peri-implant mucosa and an elevated expression of cytokines in the lymph nodes and spleen. A corresponding change in cytokine expression was detected in the ovary as well as a change in ovarian immune cell populations. These events are accompanied by elevated oxidative damage in the ovary and eventually reduced folliculogenesis and oocyte quality. Implant placement also reduced the live birth rates in mating experiments. These results show that chronic oral inflammation can affect female fertility through immune modulation in the ovaries in an animal model. These concepts can now be investigated in a human clinical setting to determine if they are conserved from mouse to human.