ORIGINAL ARTICLE
Intrauterine colonization with Gardnerella vaginalis and Mobiluncus mulieris induces maternal inflammation but not preterm birth in a mouse model
Andrea Joseph,
Emma L. Lewis,
Briana Ferguson,
Yuxia Guan,
Lauren Anton,
Michal A. Elovitz,
Corresponding Author
Andrea Joseph
Department of Obstetrics, Gynecology and Reproductive Sciences, Icahn School of Medicine, New York, New York, USA
Correspondence
Andrea Joseph, Department of Obstetrics, Gynecology and Reproductive Sciences, Icahn School of Medicine, New York, NY, USA.
Email: [email protected]
Search for more papers by this authorEmma L. Lewis
Center for Research on Reproduction and Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Search for more papers by this authorBriana Ferguson
Center for Research on Reproduction and Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Search for more papers by this authorYuxia Guan
Center for Research on Reproduction and Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Search for more papers by this authorLauren Anton
Center for Research on Reproduction and Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Search for more papers by this authorMichal A. Elovitz
Department of Obstetrics, Gynecology and Reproductive Sciences, Icahn School of Medicine, New York, New York, USA
Search for more papers by this authorAndrea Joseph,
Emma L. Lewis,
Briana Ferguson,
Yuxia Guan,
Lauren Anton,
Michal A. Elovitz,
Corresponding Author
Andrea Joseph
Department of Obstetrics, Gynecology and Reproductive Sciences, Icahn School of Medicine, New York, New York, USA
Correspondence
Andrea Joseph, Department of Obstetrics, Gynecology and Reproductive Sciences, Icahn School of Medicine, New York, NY, USA.
Email: [email protected]
Search for more papers by this authorEmma L. Lewis
Center for Research on Reproduction and Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Search for more papers by this authorBriana Ferguson
Center for Research on Reproduction and Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Search for more papers by this authorYuxia Guan
Center for Research on Reproduction and Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Search for more papers by this authorLauren Anton
Center for Research on Reproduction and Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Search for more papers by this authorMichal A. Elovitz
Department of Obstetrics, Gynecology and Reproductive Sciences, Icahn School of Medicine, New York, New York, USA
Search for more papers by this authorFirst published: 08 July 2023
Abstract
Problem
Preterm birth (PTB) remains a leading cause of childhood mortality. Recent studies demonstrate that the risk of spontaneous PTB (sPTB) is increased in individuals with Lactobacillus-deficient vaginal microbial communities. One proposed mechanism is that vaginal microbes ascend through the cervix, colonize the uterus, and activate inflammatory pathways leading to sPTB. This study assessed whether intrauterine colonization with either Gardnerella vaginalis and Mobiluncus mulieris alone is sufficient to induce maternal-fetal inflammation and induce sPTB.
Method of study
C56/B6J mice, on embryonic day 15, received intrauterine inoculation of saline or 108 colony-forming units of G. vaginalis (n = 30), M. mulieris (n = 17), or Lactobacillus crispatus (n = 16). Dams were either monitored for maternal morbidity and sPTB or sacrificed 6 h post-infusion for analysis of bacterial growth and cytokine/chemokine expression in maternal and fetal tissues.
Results
Six hours following intrauterine inoculation with G. vaginalis, M. mulieris, or L. crispatus, live bacteria were observed in both blood and amniotic fluid, and a potent immune response was identified in the uterus and maternal serum. In contrast, only a limited immune response was identified in the amniotic fluid and the fetus after intrauterine inoculation. High bacterial load (108 CFU/animal) of G. vaginalis was associated with maternal morbidity and mortality but not sPTB. Intrauterine infusion with L. crispatus or M. mulieris at 108 CFU/animal did not induce sPTB, alter pup viability, litter size, or maternal mortality.
Conclusions
Despite inducing an immune response, intrauterine infusion of live G. vaginalis or M. mulieris is not sufficient to induce sPTB in our mouse model. These results suggest that ascension of common vaginal microbes into the uterine cavity alone is not causative for sPTB.
CONFLICT OF INTEREST STATEMENT
MAE receives compensation and has equity interest in Mirvie.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
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