Editorial: Inflammation in the female genital tract

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Editorial on the Research Topic Inflammation in the female genital tract
A global call for action to become more inclusive in sex and gender differences in biological sciences has highlighted the need for more studies focused on women's health, including research in reproductive health. This special issue in Frontiers Reproductive Health is bringing forward some of the most current studies on how inflammation plays a role in women's reproductive health to highlight its impact on the female genital tract.
Women's reproductive health is largely linked with inflammatory events that can occur during a woman's lifetime. Normal reproductive function involves strict regulation of the inflammatory pathways in order to re-establish homeostasis dysregulated after sexual intercourse, birth or repair from diseases and infection. Recent literature has indicated that without proper resolution, the maintenance of a genital inflammatory state is a key factor in numerous pathologies such as pelvic inflammatory diseases and cancers, but it also increases the risk of acquiring sexual transmitted infections (STIs) or experiencing pre-term birth (Adapen et al.). Inflammation can come from many sources such as presence of an STI, changes in the vaginal microbiome, changes in hormones levels due to age or other factors, pregnancy and labour, cancers, uses of some hormonal contraceptives and sexual activities (Adapen et al.; Gholiof et al.).
Microbicides and other preventive compounds used in clinical trial to prevent STIs have showed that genital inflammation plays an important role for product effectiveness. The nonoxynol-9 microbicide, for example, failed to prevent HIV and increased the risk of acquiring HIV and other STIs. This microbicide was later associated with increase genital inflammation (1). More recently, the Caprisa 004 study showed that while the use of this gel could reduce the risk of HIV infection by 39% (2), an increased baseline genital inflammatory state was associated with negating this protective effect (3). To determine the presence of inflammation in the genital tract, the measurement of cytokines previously associated with risk of STI acquisition may be used as a guideline for evaluating novel vaginal products in clinical trials, as is Treatment of a dysbiotic microbiome, such as during bacterial vaginosis, using over the counter vaginal products is common practice for women. However, these products need to be studied to determine whether they are safe to use without causing more local inflammation. Unfortunately, the impact on the vaginal barrier and inflammation of many of these gels has not been comprehensively studied (Tyssen et al.). Happel et al. have reviewed what is needed to take into consideration when performing safety assessments during pre-clinical trials for vaginal products. These guidelines include how best to design the study by collecting numerous baseline samples, assessing the product over time, and determining the most dilute concentration of product that has the desirable effect. In addition, they have identified key cytokine biomarkers based on literature findings to evaluate safety of these products.
The assessment of available vaginal gels on the epithelial barrier and cytokine expression was performed by Tyssen et al. in this issue. They focused their study on gels that contain lactic acid, as this is an antibacterial and antiviral agent, measuring osmolality of these gels plus a few others without lactic acid, and determine using in vitro assays whether these gels damage barrier integrity measured using transepithelial electrical resistance and histology of EpiVaginal tissue models. They determined that hyperosmolal gels detrimentally affected electrical resistance, and most gels induced moderate tissue damage. This indicates the need for better evaluation of vaginal products prior to being used, by measuring not only the inflammation but also the epithelial barrier integrity (Tyssen et al.).
In summary, though many studies are now focusing on women's health, there is still a lot that needs to be done to better understand the environmental risks that are associated with poor reproductive health and acquisition of STIs. As a community, we need to characterize the natural immune environment of the female genital tract. In addition, we need to understand how vaginal products or exogenous hormones can lead to genital inflammation and epithelial damage prior to being made available for use in order to prevent any increase in risk associated with genital inflammation.

Author contributions
Each editor helped in writing the editorial and reviewing the manuscript. All authors contributed to the article and approved the submitted version.