Xenobiotic metabolites modify immune responses of the cervicovaginal epithelium: potential mechanisms underlying barrier disruption

Objective Xenobiotic metabolites are exogenous biochemicals that can adversely impact reproductive health. We previously identified xenobiotics in cervicovaginal fluid during pregnancy in association with short cervix. In other organ systems, xenobiotics can modify epithelial barrier function. We hy...

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Bibliographic Details
Published in:BJOG : an international journal of obstetrics and gynaecology 2024-04, Vol.131 (5), p.665-674
Main Authors: Gerson, Kristin D., Loder, Aaron, Landau, Zachary, Anton, Lauren
Format: Article
Language:English
Subjects:
Cell culture
Cell lines
cervicovaginal inflammation
Cervix
Chemotactic factors
Cytokines
Diethanolamine
epithelial barrier dysfunction
Epithelial cells
Epithelium
Fractalkine
Immune response
Inflammation
Interleukin 6
Leukocytes (neutrophilic)
Lymphocytes
Macrophages
Matrix metalloproteinase
Metabolites
Metalloproteinase
Monocytes
Pregnancy
Premature birth
preterm birth
RANTES
Reproductive health
Vagina
Variance analysis
Xenobiotics
γ-Interferon
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Summary:Objective Xenobiotic metabolites are exogenous biochemicals that can adversely impact reproductive health. We previously identified xenobiotics in cervicovaginal fluid during pregnancy in association with short cervix. In other organ systems, xenobiotics can modify epithelial barrier function. We hypothesise that xenobiotics dysregulate epithelial cell and macrophage immune responses as a mechanism to disrupt the cervicovaginal barrier. Design In vitro cell culture system. Setting Laboratory within academic institution. Sample Vaginal, ectocervical and endocervical epithelial cell lines and primary macrophages. Methods Cells were treated with diethanolamine (2.5 mM), ethyl glucoside (5 mM) or tartrate (2.5 mM) for 24 h. Main outcome measures Cytokines and matrix metalloproteinases were measured in cell supernatants (n = 3 per condition). One‐way analysis of variance (ANOVA) with Dunnett's test for multiple comparisons was performed. Results Diethanolamine induces inflammatory cytokines, whereas ethyl glucoside and tartrate generally exert anti‐inflammatory effects across all cells. Diethanolamine increases interleukin 6 (IL‐6), IL‐8, interferon γ‐induced protein 10 kDa (IP‐10), growth‐regulated oncogene (GRO), fractalkine, matrix metalloproteinase 1 (MMP‐1), MMP‐9 and MMP‐10 (p 
ISSN:1470-0328
1471-0528
DOI:10.1111/1471-0528.17654