The circadian phase of antenatal glucocorticoid treatment affects the risk of behavioral disorders

Mariana Astiz (), Isabel Heyde, Mats Ingmar Fortmann, Verena Bossung, Claudia Roll, Anja Stein, Berthold Grüttner, Wolfgang Göpel, Christoph Härtel, Jonas Obleser and Henrik Oster ()
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Mariana Astiz: University of Lübeck. Marie-Curie-Straße
Isabel Heyde: University of Lübeck. Marie-Curie-Straße
Mats Ingmar Fortmann: University of Lübeck
Verena Bossung: Department of Women’s Health and Obstetrics University of Lübeck
Claudia Roll: University Witten/Herdecke
Anja Stein: University Hospital Essen
Berthold Grüttner: Faculty of Medicine and University Hospital Cologne, University of Cologne
Wolfgang Göpel: University of Lübeck
Christoph Härtel: University of Lübeck
Jonas Obleser: University of Lübeck
Henrik Oster: University of Lübeck. Marie-Curie-Straße

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract During pregnancy, maternal endocrine signals drive fetal development and program the offspring’s physiology. A disruption of maternal glucocorticoid (GC) homeostasis increases the child’s risk of developing psychiatric disorders later in life. We here show in mice, that the time of day of antenatal GC exposure predicts the behavioral phenotype of the adult offspring. Offspring of mothers receiving GCs out-of-phase compared to their endogenous circadian GC rhythm show elevated anxiety, impaired stress coping, and dysfunctional stress-axis regulation. The fetal circadian clock determines the vulnerability of the stress axis to GC treatment by controlling GC receptor (GR) availability in the hypothalamus. Similarly, a retrospective observational study indicates poorer stress compensatory capacity in 5-year old preterm infants whose mothers received antenatal GCs towards the evening. Our findings offer insights into the circadian physiology of feto-maternal crosstalk and assign a role to the fetal clock as a temporal gatekeeper of GC sensitivity.

Date: 2020
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DOI: 10.1038/s41467-020-17429-5

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