Astiz, Mariana ORCID: 0000-0001-9912-1686, Heyde, Isabel, Fortmann, Mats Ingmar, Bossung, Verena, Roll, Claudia, Stein, Anja, Gruettner, Berthold, Goepel, Wolfgang, Haertel, Christoph, Obleser, Jonas ORCID: 0000-0002-7619-0459 and Oster, Henrik (2020). The circadian phase of antenatal glucocorticoid treatment affects the risk of behavioral disorders. Nat. Commun., 11 (1). LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Astiz, MarianaUNSPECIFIEDorcid.org/0000-0001-9912-1686UNSPECIFIED
Heyde, IsabelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fortmann, Mats IngmarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bossung, VerenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roll, ClaudiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stein, AnjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gruettner, BertholdUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goepel, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haertel, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Obleser, JonasUNSPECIFIEDorcid.org/0000-0002-7619-0459UNSPECIFIED
Oster, HenrikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-326181
DOI: 10.1038/s41467-020-17429-5
Journal or Publication Title: Nat. Commun.
Volume: 11
Number: 1
Date: 2020
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PITUITARY-ADRENAL AXIS; EMBRYONIC-DEVELOPMENT; DNA DEMETHYLATION; STRESS; CLOCK; EXPRESSION; RHYTHMS; DEHYDROGENASE; RECEPTOR; GENESMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/32618

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