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The Protective Role of Cervical Mucus in Maintaining Vaginal Health

/ by Lifeline® Cell Technology

Cervical Health Awareness Month

Cervical health is a crucial yet often overlooked aspect of overall well-being. The cervix is a small but mighty organ that is integral for fertility, pregnancy, and childbirth. However, it is susceptible to infections and cancer, including bacterial vaginosis (BV), human papillomavirus (HPV), and cervical cancer.

While infection with high-risk HPV is the primary cause of cervical cancer, growing evidence shows that the cervicovaginal microenvironment influences susceptibility to HPV infection. One of the most common disruptors of this environment is BV, which shifts the microbiome from protective lactobacilli to harmful anaerobic bacteria, including Gardnerella vaginalis. This dysbiosis alters vaginal pH, weakens mucosal barrier function, and promotes local inflammation, which makes the cervix more prone to viral infection.

Understanding how BV-associated microbiome changes affect cervical epithelial biology can help researchers identify effective prevention and therapeutic strategies. In this blog, we highlight a recent publication that leverages human organ-on-a-chip microfluidic culture technology to directly investigate how cervical mucus secretions can modulate the human vaginal epithelium under both healthy and dysbiotic conditions caused by BV.

Modeling Vaginal Dysbiosis Using Human Organ-on-a-Chip Technology

The cervicovaginal fluid that covers the surface of the vaginal epithelium is essential to women’s health and reproductive functions. Aside from its function as a physical barrier protecting against environmental pathogens, whether cervical mucus has an active immunomodulatory role is unclear. Gutziet et al. leveraged human vagina and cervix organ-on-a-chip models to investigate if cervical mucus can directly regulate the vaginal microbiome to protect against dysbiosis.

To build these models, primary human vaginal epithelial cells and primary cervical epithelial cells from Lifeline® Cell Technology cultured in ReproLife™ media were used to generate the human Vagina Chip and Cervix Chip, respectively. In each chip system, epithelial cells are interfaced with stromal or cervical fibroblasts across an extracellular matrix (ECM)–coated porous membrane. The Cervix Chip produces cervical mucus with in vivo–like physical and chemical properties, which was collected and perfused through the epithelial channel of the Vagina Chip to simulate the flow of cervical mucus through the reproductive tract. This coupled organ-chip approach supports direct analysis of human host–microbiome interactions within the Vagina Chip.

Exposure of the Vagina Chip to cervical mucus resulted in statistically significant reductions in multiple proinflammatory cytokines, including interleukin-1α (IL-1α), IL-1β, and macrophage inflammatory protein-1β (MIP-1β), along with a concomitant increase in anti-inflammatory IL-10 protein levels after 24 hours compared to control Vagina Chips without mucus. This shows the mucus-containing secretions produced by human cervical epithelium can directly modulate vaginal epithelial inflammatory responses, even in the absence of immune cells.

The authors next examined the impact of cervical mucus on a dysbiotic (non-optimal) vaginal microbiome by inoculating Vagina Chips with a BV-associated consortium (BVC1) consisting of G. vaginalis E2 and E4, Prevotella bivia BHK8, and Atopobium vaginae. In the presence of mucus-containing effluents from the Cervix Chip, BVC1 colonization of the vaginal epithelium was significantly inhibited. These Vagina Chips showed lower numbers of viable bacteria, reduced bacterial adhesion to epithelial cells, and decreased secretion of proinflammatory cytokines including IL-8, IL-1α, TNF-α, MIP-1β, RANTES (CCL5), and IL-10. These results indicate that cervical mucus can induce protective vaginal epithelial responses that actively suppress bacterial growth.

To investigate the mechanisms involved in the protective effect of the cervical mucus, the authors analyzed the secretome of the Vagina Chip before and after exposure to Cervix Chip effluents using mass spectrometry. Several proteins and antimicrobial peptides were upregulated that are likely involved in protection against dysbiotic microbiota, inflammation, and vaginal epithelial injury. Notably, the expression of N-acetylglucosamine-6-sulfatase (GNS) was downregulated. Reduced GNS expression may inhibit bacterial growth by preventing mucin degradation, a process that facilitates BV-associated bacterial colonization. Additionally, STRING analysis revealed a significant proportion of the differentially expressed proteins were associated with exosomes, suggesting a potential role for extracellular vesicles in mediating these protective responses.

Together, the findings from this study show the active role of cervical mucus in maintaining vaginal health. Importantly, the identification of mucus-regulated proteins also points to potential biomarkers for diagnostic and therapeutic development. More broadly, this work demonstrates the value of human organ-on-a-chip technology (Vagina Chip and Cervix Chip) as a translationally-relevant model for studying vaginal biology to identify new targets for the diagnosis and treatment of vaginal disorders.

Lifeline Cell Technology Female Reproductive Cells and Media

Lifeline Cell Technology provides a comprehensive portfolio of primary female reproductive cells directly isolated from source tissue, along with specialized media formulations optimized to preserve cell phenotypes in vitro. These products enable researchers to build advanced human-relevant models, such as the cervix and vagina organ-on-a-chip systems highlighted in this study.

Explore our blog to see how our cells and culture media are advancing biomedical research worldwide. If you have used our products in your publication, we’d love to feature your work here!

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