Affiliation:
1. Center for Research on Reproduction and Women's Health, Department of Obstetrics and Gynecology, Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USA
2. Department of Microbiology, Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USA
Abstract
AbstractObjectiveXenobiotic 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.DesignIn vitro cell culture system.SettingLaboratory within academic institution.SampleVaginal, ectocervical and endocervical epithelial cell lines and primary macrophages.MethodsCells were treated with diethanolamine (2.5 mM), ethyl glucoside (5 mM) or tartrate (2.5 mM) for 24 h.Main outcome measuresCytokines 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.ResultsDiethanolamine 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 < 0.05 for all), factors involved in acute inflammation and recruitment of monocytes, neutrophils and lymphocytes. Ethyl glucoside and tartrate decrease multiple cytokines, including RANTES and MCP‐1 (p < 0.05 for all), which serve as chemotactic factors. Vaginal cells exhibit heightened inflammatory tone compared with cervical cells and macrophages, with a greater number of differentially expressed analytes after xenobiotic exposure.ConclusionsXenobiotic metabolites present in the cervicovaginal space during pregnancy modify immune responses, unveiling potential pathways through which environmental exposures may contribute to the pathogenesis of cervical remodelling preceding preterm birth. Future work identifying xenobiotic sources and routes of exposure offers the potential to modify environmental risks to improve pregnancy outcomes.
Subject
Obstetrics and Gynecology
Cited by
1 articles.
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