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Intraamniotic Lipopolysaccharide Exposure Changes Cell Populations and Structure of the Ovine Fetal Thymus

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Abstract

Rationale

Chorioamnionitis induces preterm delivery and acute involution of the fetal thymus which is associated with postnatal inflammatory disorders. We studied the immune response, cell composition, and architecture of the fetal thymus following intraamniotic lipopolysaccharide (LPS) exposure.

Methods

Time-mated ewes received an intraamniotic injection of LPS 5, 12, or 24 hours or 2, 4, 8, or 15 days before delivery at 125 days gestational age (term = 150 days).

Results

The LPS exposure resulted in decreased blood lymphocytes within 5 hours and decreased thymic corticomedullary ratio within 24 hours. Thymic interleukin 6 (IL6) and IL17 messenger RNA (mRNA) increased 5-fold 24 hours post-LPS exposure. Increased toll-like receptor 4 (TLR4) mRNA and nuclear factor κB positive cells at 24 hours after LPS delivery demonstrated acute thymic activation. Both TLR4 and IL1 mRNA increased by 5-fold and the number of Foxp3-positive cells (Foxp3+ cells) decreased 15 days after exposure.

Conclusion

Intraamniotic LPS exposure caused a proinflammatory response, involution, and a persistent depletion of thymic Foxp3+ cells indicating disturbance of the fetal immune homeostasis.

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Authors and Affiliations

  1. Department of Pediatrics, School for Oncology and Developmental Biology, School for Mental Health and Neuroscience, Maastricht University Medical Center, Postbus 5800, 6202 AZ, Maastricht, the Netherlands

    Elke Kuypers MSc, Tim G. A. M. Wolfs PhD, Jennifer J. P. Collins MSc, Reint K. Jellema MD, MSc & Boris W. Kramer MD, PhD

  2. School of Women’s and Infants’ Health, The University of Western Australia, Perth, WA, Australia

    John P. Newnham MD, Matthew W. Kemp PhD, Suhas G. Kallapur MD & Alan H. Jobe MD, PhD

  3. Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA

    Suhas G. Kallapur MD, Alan H. Jobe MD, PhD & Boris W. Kramer MD, PhD

Authors
  1. Elke Kuypers MSc
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  2. Tim G. A. M. Wolfs PhD
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  3. Jennifer J. P. Collins MSc
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  4. Reint K. Jellema MD, MSc
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  5. John P. Newnham MD
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  6. Matthew W. Kemp PhD
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  7. Suhas G. Kallapur MD
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  8. Alan H. Jobe MD, PhD
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  9. Boris W. Kramer MD, PhD
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Corresponding author

Correspondence to Boris W. Kramer MD, PhD.

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Kuypers, E., Wolfs, T.G.A.M., Collins, J.J.P. et al. Intraamniotic Lipopolysaccharide Exposure Changes Cell Populations and Structure of the Ovine Fetal Thymus. Reprod. Sci. 20, 946–956 (2013). https://doi.org/10.1177/1933719112472742

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