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

First Author  Astiz M Year  2020
Journal  Nat Commun Volume  11
Issue  1 Pages  3593
PubMed ID  32681096 Mgi Jnum  J:293822
Mgi Id  MGI:6447955 Doi  10.1038/s41467-020-17429-5
Citation  Astiz M, et al. (2020) The circadian phase of antenatal glucocorticoid treatment affects the risk of behavioral disorders. Nat Commun 11(1):3593
abstractText  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.
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