Oral microenvironmental dysregulation and female reproductive health: clinical evidence, immunological mechanisms, and bidirectional crosstalk
Oral microenvironmental dysregulation, particularly at the periodontal interface, represents a potential source of microbial and host-derived signals that may influence female reproductive health through host–microbiome interactions and immune-mediated inflammatory pathways. Clinical and epidemiological studies have reported associations between oral or periodontal conditions and bacterial vaginosis, fecundability, time to conception, polycystic ovary syndrome, and other gynaecological conditions; however, the evidence remains heterogeneous and causal relationships are not established. Most available clinical evidence is observational, while many of the proposed molecular and tissue-level mechanisms are supported by experimental or indirect evidence, with the strength of support varying across reproductive outcomes and biological pathways. This review synthesises current clinical evidence and discusses the biological and immunological mechanisms potentially linking oral and periodontal dysregulation with female reproductive health. At the periodontal interface, community-level microbial dysbiosis, altered physicochemical conditions, non-resolving inflammation, and epithelial barrier impairment may disrupt mucosal homeostasis and permit microbial products and host-derived inflammatory signals to access systemic circulation. These signals may subsequently be amplified through innate immune activation, altered myeloid-cell responses, endothelial dysfunction, oxidative stress, and metabolic pathways, thereby modifying tissue-specific responses in the cervicovaginal mucosa, endometrium, ovary, and gestational tissues. Direct haematogenous dissemination of oral microorganisms appears biologically plausible in selected intrauterine infections, whereas systemic host-mediated mechanisms may better explain the broader spectrum of reported oral–reproductive associations. Conversely, hormonal fluctuations and endocrine-metabolic disturbances may alter periodontal susceptibility and inflammatory responses to dental biofilm. Current evidence supports biologically plausible and potentially bidirectional interactions between oral mucosal dysregulation and female reproductive health, although their direction, magnitude, disease specificity, and clinical significance remain incompletely defined. Future longitudinal and interventional studies integrating periodontal phenotyping, microbiome profiling, immune-metabolic assessment, and reproductive evaluation are required to clarify temporal relationships and biological mediation.
Authors
- Lin Sun (ORCID: https://orcid.org/0000-0001-7496-7685)
- Matthias Hannig (ORCID: https://orcid.org/0000-0003-0669-6881)
- Changfeng Qu
- Bo Lei
- Jie Yu
- Ming Zhang
- Yong Liu
Institutions
- Dalian University of Technology (CN)
- Second Affiliated Hospital of Dalian Medical University (CN)
- Saarland University (DE)
Publication Details
- Journal
- Frontiers in Immunology
- Published
- 2026-11-02
- DOI
- https://doi.org/10.3389/fimmu.2026.2000537
- Primary Topic
- Oral microbiology and periodontitis research
- Type
- article
- Field-Weighted Citation Impact
- 0.00