Sex dimorphism in periodontitis in animal models

Although surveys in the USA have shown that male subjects are more prone to develop periodontitis, sex as a risk factor in periodontitis, and its mechanism, remain controversial. Animal models are ideal for investigating immunological mechanisms of sex dimorphism in periodontitis because in these models it is possible to exclude the interference of gender-related risk factors, such as smoking and oral hygiene habits. Based on surveys in humans and reports on sex dimorphism in other diseases, our hypothesis is that sex is a risk factor in periodontitis.

Different murine models (oral gavage model and ligature model) for periodontitis have been utilized to determine susceptibility to periodontitis in female and male mice. Periodontal bone levels were measured as the distance from the cemento-enamel junction to the alveolar bone crest (CEJ-ABC) in young female or male mice (8-10 wk of age). Differential expression of inflammatory mediators in the gingivae of female and male mice was determined by quantitative real-time PCR.

In comparison with male mice, female mice displayed significantly (p < 0.05) increased periodontal bone loss, accompanied by elevated expression of proinflammatory cytokines (interleukin-1β, interleukin-6 and interleukin-17A) and higher numbers of oral bacteria.

In contrast to the results in humans, in which periodontitis susceptibility is also influenced by confounding gender-related behaviors, in the murine oral gavage model and ligature model, female mice appear to be more susceptible to periodontal bone loss than male mice. In the ligature model, we observed significantly (p < 0.05) higher CEJ-ABC distance, gingival proinflammatory cytokine production and number of oral bacteria in female mice. Furthermore, our results imply that female mice develop periodontitis with a higher progression rate. Our study has therefore established that animal models can be used to dissect the mechanisms underlying genuine gender-based differences in periodontal disease susceptibility and/or progression.