Probing the direct effects of endocrine disrupting chemicals on the vaginal microenvironment

/Abstract The vaginal microenvironment is a complex and dynamic system that regulates female reproductive health through interactions between microbes, mammalian cells, and mucus. Changes to any one of these axes may lead to increased inflammation in the female reproductive tract and an increased susceptibility for vaginal dysbiosis. In an optimal microenvironment, bacteria in the vagina produce lactic acid and hydrogen peroxide, maintaining a dominance of lactobacilli. In dysbiosis, there is a polymicrobial microbiome, with species that degrade mucus and epithelial barriers, leading to inflammation, and facilitating infection. Fluctuations in the composition and function of vaginal flora across the reproductive stages of a woman’s life are normal and are primarily driven by changes in estrogen. A non-optimal, polymicrobial microbiome is found in approximately 30% of women in the United States, and contributes to reproductive diseases including preterm birth, infertility, and risk for sexually transmitted infections. However the factors and mechanisms that promote a dysbiotic vaginal environment remain unclear. Endocrine disrupting chemicals (EDCs) interfere with hormone action in the body and represent an under-investigated potential risk factor for dysbiosis. Exposure to phthalates, EDCs that have been shown to interfere with estrogen signaling, is of significant concern for women’s reproductive health due to frequent exposure and associations with adverse reproductive outcomes. Phthalates are commonly found in feminine hygiene products such as pads, panty liners, tampons, and vaginal douches, sprays, powders, and wipes. To date, only one study has investigated associations between systemic phthalate exposure and composition of the vaginal microbiome, showing that some phthalates are associated with dysbiosis. The effects of phthalates on the viability and function of microbes, mammalian cells, and mucus in the vaginal environment remain unknown. Here, we propose to evaluate the how direct phthalate exposure impacts (1) microbial viability and function; (2) mammalian cell viability and function; and (3) mucosal barrier properties. Our proposed Aims will test the hypothesis that phthalates disrupt the vaginal microenvironment and contribute to disparate adverse reproductive health outcomes associated with dysbiosis. Completion of this work will provide a foundation and preliminary data to motivate the study of local phthalate exposures in at-risk populations with additional gynecologic indications. By understanding how the vaginal environment is directly affected by phthalate exposures, we will identify opportunities for intervention to promote healthy female reproductive outcomes. Project Number: 1R21ES037883-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Environmental Health Sciences (NIEHS) | Principal Investigator: Hannah Zierden-Shininger | Institution: UNIV OF MARYLAND, COLLEGE PARK, COLLEGE PARK, MD | Award Amount: $426,346 | Activity Code: R21 | Study Section: Integrative and Clinical Endocrinology and Reproduction Study Section[ICER] View on NIH RePORTER: https://reporter.nih.gov/project-details/11374712