Chronic Intestinal Inflammation and Microbial Dysbiosis Are Associated With Female Reproductive Outcomes in a Mouse Model of Inflammatory Bowel Disease
Background and Aims: The mechanism for increased infertility and adverse pregnancy outcomes in women with active inflammatory bowel disease is unknown. We aimed to create a murine model of chronic gut inflammation to study the pathogenesis of reproductive outcomes in inflammatory bowel disease. Meth...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-01-01
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| Series: | Gastro Hep Advances |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772572325000573 |
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| Summary: | Background and Aims: The mechanism for increased infertility and adverse pregnancy outcomes in women with active inflammatory bowel disease is unknown. We aimed to create a murine model of chronic gut inflammation to study the pathogenesis of reproductive outcomes in inflammatory bowel disease. Methods: Chronic intestinal inflammation was induced with dextran sodium sulfate (DSS) in specific-pathogen–free (SPF) female mice. SPF mice not treated with DSS served as controls. Daily estrous cycle monitoring was performed. Age-matched groups were cohabitated with SPF males for mating purposes. Pup weights, litter sizes, reproductive hormone serologies, peripheral and mucosal immune changes, and 16S rRNA gene taxonomic profiling of the fecal microbiome were measured and characterized. Results: DSS treatment led to weight loss, increased disease activity index scores, and reduced colon lengths. Compared to SPF controls, DSS mice spent less time in the estrus phase of the reproductive cycle (P < .05) and had decreased litter sizes and pup weights (P < .05). DSS-treated mice had lower anti-müllerian hormone and luteinizing hormone (P < .05) concentrations and higher estradiol (P < .05) concentrations. Among DSS mice, Turicibacter abundance correlated positively with the proportion of circulating neutrophils and proinflammatory cytokines and serum estradiol (Spearman ρ = 0.538–0.650, P < .001–.002). Lactobacillus and Prevotellaceae positively correlated with pup weights, litter size, estrus phase duration, luteinizing hormone, and immune cell changes from the colon and peripheral blood (ρ = 0.475–0.695, P < .01). Conclusion: Chronic bowel inflammation induces gut dysbiosis and likely contributes to adverse reproductive outcomes through endocrine imbalances. Further investigation with human studies is needed. |
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| ISSN: | 2772-5723 |