Researchers have developed human Cervix Chip models that replicate the physiology of the endocervical and ectocervical mucosa and their responses to microenvironmental, hormonal, and microbiome influences, as detailed in a recent study.

Published in Nature Communications, the study demonstrated that Cervix Chips exhibited variations when populated with different microbial communities, dominated by Lactobacillus crispatus and Gardnerella vaginalis, respectively. These variations were observed in tissue innate immune responses, barrier function, cell viability, proteome, and mucus composition, mirroring in vivo differences.

Dynamic flow conditions influenced cervical epithelial cell differentiation, mucus composition, and innate immune responses. Periodic flow promoted an endocervical phenotype, while continuous flow induced an ectocervical phenotype. Colonization with L. crispatus resulted in a stable epithelial layer, robust barrier function, a quiescent immune state, and mucus production with a clinically relevant composition. In contrast, co-culture with G. vaginalis led to epithelial damage, cell death, compromised barrier integrity, altered mucus properties, and an enhanced inflammatory response.

Detailed Findings

Innate Immune Responses: The study measured cytokine levels in the Cervix Chips under different microbial colonization conditions. Colonization with L. crispatus led to a decrease in pro-inflammatory cytokines such as interleukin (IL)-1α, IL-1β, and IL-6. Conversely, G. vaginalis colonization resulted in increases in these cytokines.

Proteome Analysis: Proteomic analysis revealed that L. crispatus colonization upregulated proteins associated with healthy tissue development and immune regulation, such as cysteine and glycine-rich protein 1 (CSRP1) and cystatin-B (CSTB). In contrast, G. vaginalis colonization upregulated proteins linked to cell apoptosis, tissue damage, and inflammation, including human leukocyte antigen (HLA)-C and tripartite motif-containing protein 25 (TRIM25).

Mucus Composition: Glycomic analysis showed that the mucus produced under different flow conditions varied in glycan composition. Continuous flow led to a more diverse array of O- and N-glycans, resembling clinical cervical mucus samples. The presence of L. crispatus maintained high levels of protective sialylated O-glycans, while G. vaginalis reduced these sialylated structures, increasing the abundance of undecorated O-glycans associated with dysbiosis.

Ethics declarations can be found in the study.