Inflammation-induced preterm birth alters neuronal morphology in the mouse fetal brain

Authors

  • Irina Burd,

    Corresponding author
    1. Maternal and Child Health Research Program, Department of Obstetrics and Gynecology, Center for Research on Reproduction and Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania
    • Maternal and Child Health Research Program, Department of Obstetrics and Gynecology; Center for Research on Reproduction and Women's Health University of Pennsylvania, 1353 Biomedical Research Bldg. II/III, 421 Curie Boulevard, Philadelphia, PA 19104-6142
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    • The first two authors contributed equally to this work.

  • Amy I. Bentz,

    1. Maternal and Child Health Research Program, Department of Obstetrics and Gynecology, Center for Research on Reproduction and Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania
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    • The first two authors contributed equally to this work.

  • Jinghua Chai,

    1. Maternal and Child Health Research Program, Department of Obstetrics and Gynecology, Center for Research on Reproduction and Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania
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  • Juan Gonzalez,

    1. Maternal and Child Health Research Program, Department of Obstetrics and Gynecology, Center for Research on Reproduction and Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania
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  • Hubert Monnerie,

    1. Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania
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  • Peter D. Le Roux,

    1. Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania
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  • Akiva S. Cohen,

    1. Department of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Marc Yudkoff,

    1. Division of Child Development, Rehabilitation Medicine and Metabolic Disease, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Michal A. Elovitz

    1. Maternal and Child Health Research Program, Department of Obstetrics and Gynecology, Center for Research on Reproduction and Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania
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Abstract

Adverse neurological outcome is a major cause of long-term morbidity in ex-preterm children. To investigate the effect of parturition and inflammation on the fetal brain, we utilized two in vivo mouse models of preterm birth. To mimic the most common human scenario of preterm birth, we used a mouse model of intrauterine inflammation by intrauterine infusion of lipopolysaccharide (LPS). To investigate the effect of parturition on the immature fetal brain, in the absence of inflammation, we used a non-infectious model of preterm birth by administering RU486. Pro-inflammatory cytokines (IL-10, IL-1β, IL-6 and TNF-α) in amniotic fluid and inflammatory biomarkers in maternal serum and amniotic fluid were compared between the two models using ELISA. Pro-inflammatory cytokine expression was evaluated in the whole fetal brains from the two models. Primary neuronal cultures from the fetal cortex were established from the different models and controls in order to compare the neuronal morphology. Only the intrauterine inflammation model resulted in an elevation of inflammatory biomarkers in the maternal serum and amniotic fluid. Exposure to inflammation-induced preterm birth, but not non-infectious preterm birth, also resulted in an increase in cytokine mRNA in whole fetal brain and in disrupted fetal neuronal morphology. In particular, Microtubule-associated protein 2 (MAP2) staining was decreased and the number of dendrites was reduced (P < 0.001, ANOVA between groups). These results suggest that inflammation-induced preterm birth and not the process of preterm birth may result in neuroinflammation and alter fetal neuronal morphology. © 2010 Wiley-Liss, Inc.

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