Can Carbon Monoxide Prevent Infection-Mediated Preterm Birth in a Mouse Model?

Authors

  • Morgan R. Peltier,

    1. Women and Children's Research Laboratory, Winthrop University Hospital, Mineola, NY, USA
    2. Department of Obstetrics and Gynecology, Winthrop University Hospital, Mineola, NY, USA
    3. Department of Obstetrics, Gyneocology and Reproductive Medicine, SUNY Stony Brook, Stony Brook, NY, USA
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    • These authors contributed equally to this paper.
  • Hschi-Chi Koo,

    1. Women and Children's Research Laboratory, Winthrop University Hospital, Mineola, NY, USA
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    • These authors contributed equally to this paper.
  • Ellen M. Gurzenda,

    1. Women and Children's Research Laboratory, Winthrop University Hospital, Mineola, NY, USA
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    • These authors contributed equally to this paper.
  • Yuko Arita,

    1. Women and Children's Research Laboratory, Winthrop University Hospital, Mineola, NY, USA
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  • Natalia G. Klimova,

    1. Women and Children's Research Laboratory, Winthrop University Hospital, Mineola, NY, USA
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  • Niccole Olgun,

    1. Women and Children's Research Laboratory, Winthrop University Hospital, Mineola, NY, USA
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  • Nazeeh Hanna

    Corresponding author
    1. Department of Pediatrics, Winthrop University Hospital, Mineola, NY, USA
    • Women and Children's Research Laboratory, Winthrop University Hospital, Mineola, NY, USA
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Correspondence

Nazeeh Hanna, Department of Pediatrics, Winthrop University Hospital, 259 1st Street, Mineola, NY, USA.

E-mail: nhanna@winthrop.org

Abstract

Problem

Preterm birth is frequently caused by intrauterine infection and inflammation. Recent studies have demonstrated that carbon monoxide (CO), which is produced endogenously, has potent anti-inflammatory properties. Whether or not CO can prevent infection-mediated preterm birth is unknown.

Methods

Mice were assigned to one of four groups: sham infection, sham infection + CO, infection, or infection + CO. Infections were established by intra-uterine injection of Escherichia coli on day 14 of pregnancy. Animals received daily i.p. injections of 1 mL CO-saturated lactated ringers solution (LRS) or LRS alone beginning on the morning of surgery. Gestational age at delivery and litter characteristics was noted. In second experiment, animals were sacrificed 24 hrs post-surgery and tissues were harvested for cytokine analyses.

Results

Escherichia coli intrauterine infection increased the number of animals delivering preterm. This effect was significantly ameliorated by CO-LRS. CO-treatment also increased litter size and weights of the surviving offspring. Cytokines in the amniotic fluid and the placenta were increased by E. coli exposure, but CO had no detectible effect on E. coli-stimulated cytokine production. No effects of CO were detected in sham-infected animals.

Conclusion

Supplemental CO improves pregnancy outcome after intrauterine infection and may function at a point downstream of, or through pathways independent of, induction of proinflammatory cytokines.

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