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Intrauterine Candida albicans Infection Causes Systemic Fetal Candidiasis With Progressive Cardiac Dysfunction in a Sheep Model of Early Pregnancy

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Abstract

Introduction

Several recent studies have identified a potential role for intrauterine Candida albicans in adverse pregnancy outcomes, including preterm birth. There is, however, a limited understanding of the impact of intrauterine Candida infection on fetal well-being in early pregnancy. Using a sheep model of early pregnancy, the aims of this study were to determine (I) the ability of experimentally induced intrauterine C albicans to infect the fetus and (2) whether C albicans exposure in early pregnancy is associated with alterations in fetal cardiac function, as measured by spectral tissue Doppler imaging analysis of fetal cardiac function.

Methods

Merino ewes carrying singleton pregnancies at 89 days’ gestation (term is ~ 150 days) received C albicans (n = 8) via ultrasound-guided intra-amniotic injection. Saline-exposed fetuses served as controls (n = 6). Spectral tissue Doppler imaging echocardiography and amniotic fluid collection were performed at baseline and 24 and 72 hours after intrauterine C albicans injection. Fetal tissues were collected at postmortem for analysis of infection and inflammation.

Results

Relative to saline control, intrauterine C albicans infection resulted in pronounced increases in amniotic fluid tumor necrosis factor α (TNF-α; P <.05) and cytokine/chemokine messenger RNA (interleukin [IL] Iβ, IL-6, TNF-α, and monocyte chemoattractant protein I; P <.05) in the fetal myocardium, lung, skin, and liver at 72 and 96 hours postinfection. Spectral tissue Doppler imaging showed diastolic dysfunction at 24 hours and severe biventricular diastolic dysfunction 72 hours postinfection.

Conclusion

Intrauterine C albicans infection in a sheep model of early pregnancy causes systemic fetal candidiasis, which is associated with a robust systemic inflammatory response and progressive cardiac dysfunction detectable by spectral tissue Doppler imaging.

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Authors and Affiliations

  1. Tommy’s Centre for Maternal and Fetal Health, MRC Centre for Reproductive Health, University of Edinburgh Queen’s Medical Research Institute, Edinburgh, Scotland

    Sarah J. Stock MBChB, PhD & Demelza J. Ireland PhD

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

    Sarah J. Stock MBChB, PhD, Scott White MBBS, Lucy L. Furfaro BSc, Matthew S. Payne PhD, Andres Noé MBBS, Rory Watts MPH, Sean Carter MBBS, John P. Newnham MD & Matthew W. Kemp PhD

  3. Fetal Medicine Unit, St George’s, University of London, London, UK

    Olga Patey MSc & Basky Thilaganathan MBBS, PhD

  4. Institute of Molecular and Experimental Medicine, Cardiff University, Cardiff, UK

    Owen B. Spiller PhD

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

    Alan H. Jobe MD, PhD

Authors
  1. Sarah J. Stock MBChB, PhD
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  2. Olga Patey MSc
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  3. Basky Thilaganathan MBBS, PhD
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  4. Scott White MBBS
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  5. Lucy L. Furfaro BSc
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  6. Matthew S. Payne PhD
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  8. Andres Noé MBBS
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  11. Demelza J. Ireland PhD
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  12. Alan H. Jobe MD, PhD
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  13. John P. Newnham MD
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  14. Matthew W. Kemp PhD
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Corresponding author

Correspondence to Sarah J. Stock MBChB, PhD.

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Stock, S.J., Patey, O., Thilaganathan, B. et al. Intrauterine Candida albicans Infection Causes Systemic Fetal Candidiasis With Progressive Cardiac Dysfunction in a Sheep Model of Early Pregnancy. Reprod. Sci. 24, 77–84 (2017). https://doi.org/10.1177/1933719116649697

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  • DOI: https://doi.org/10.1177/1933719116649697

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