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Antenatal endogenous and exogenous glucocorticoids and their impact on immune ontogeny and long-term immunity

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Abstract

Endogenous levels of glucocorticoids rise during pregnancy to warrant development and maturation of the fetal organs close to birth. However, during most of the gestation, the fetus is protected from excessive biologically active endogenous glucocorticoids by placental and fetal expression of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2). Maternal stress, which may overwhelm placental 11β-HSD2 activity with high glucocorticoid levels, or administration of synthetic glucocorticoids to improve the survival chances of the premature newborn, are associated to postnatal increased risk for immune diseases. Fetal exposure to excessive glucocorticoids may underlie this altered postnatal immunity. Here, we revise the role that placental and fetal 11β-HSD2, fetal glucocorticoid exposure, and programming of the offspring’s the hypothalamic-pituitary-adrenal (HPA) axis play on concerted steps in immune fetal development. We could identify gaps in knowledge about glucocorticoid-induced programming of immune diseases. Finally, based on current evidence about glucocorticoid and HPA axis-mediated immune regulation, we hypothesize on mechanisms that could drive the enhanced risk for atopies, infections, and type I diabetes in offspring that were prenatally exposed to glucocorticoids.

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Acknowledgments

Our (MES and ET) research is supported by the German Research Council (DFG), through the KFO296 and by the British Heart Foundation, Medical Research Council and Wellcome Trust (MCH, KEC). We thank D. Riller for excellent graphical work.

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    Authors and Affiliations

    1. Department of Obstetrics and Prenatal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

      María Emilia Solano

    2. University/BHF Centre for Cardiovascular Science, University of Edinburgh, Queen’s Medical Research Institute, Edinburgh, EH16 4TJ, UK

      Megan C. Holmes & Karen E. Chapman

    3. Laboratory of Immune Regulation, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

      Paul R. Mittelstadt

    4. Department of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

      Eva Tolosa

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    1. María Emilia Solano
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    Correspondence to María Emilia Solano.

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    This article is a contribution to the special issue on Fetomaternal Cross Talk and its Effect on Pregnancy Maintenance, Maternal and Offspring Health - Guest Editor: Petra Arck

    Karen E. Chapman and Eva Tolosa contributed equally to this work.

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    Solano, M.E., Holmes, M.C., Mittelstadt, P.R. et al. Antenatal endogenous and exogenous glucocorticoids and their impact on immune ontogeny and long-term immunity. Semin Immunopathol 38, 739–763 (2016). https://doi.org/10.1007/s00281-016-0575-z

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