Work

Dexamethasone affects the circadian clock in the fetal mouse suprachiasmatic nucleus at the transcriptional level

Year: 2026

Type: article

Abstract: Dexamethasone (DEX) is used in clinical practice as a life-saving therapy in threatened preterm birth; however, such treatment also represents a powerful signal that can reprogram fetal physiology, including the circadian system. The effect of DEX on the fetal circadian clock in the suprachiasmatic nuclei (SCN) has been demonstrated, but the underlying mechanism has been unaddressed. The aim of this study was to provide insight into the DEX-induced transcriptional effects in the fetal SCN of mPer2 Luc mice. We used triple-labeled immunofluorescence to localize glucocorticoid receptors (GR) in the fetal SCN, cultured ex vivo fetal SCN explants to monitor PER2-driven bioluminescence (PER2::LUC) rhythms, and RNA-seq and RT qPCR analyses to identify genes differentially expressed after DEX and vehicle treatments. We demonstrate that GRs are homogenously expressed in all cells (neuronal and glial nuclei and glial processes) of the fetal SCN. Monitoring PER2::LUC in fetal SCN explants confirmed that most cells respond to DEX with increased amplitude and mesor of the rhythms. The RNA-seq and RT-qPCR data revealed that DEX increases expression of GR-sensitive clock gene Per1 and changes the expression of other genes that may affect the clock (e.g., Hif3a , Klf9 , Zbtb16, Mt1–3 ). The effects were more significant when the treatment timing matched the temporal window of highest sensitivity of the SCN clock to DEX. Our findings advance the largely unexplored field of chrono-ontogenesis and define the effects of DEX on the fetal brain transcriptional landscape, with specific implications for the circadian clock. • Glucocorticoids affect the fetal SCN circadian clock through an unknown mechanism. • GRs are uniformly expressed in neurons and glial cells of the fetal SCN. • DEX alters PER2-driven bioluminescence rhythms in most cells of the fetal SCN. • DEX affects expression of the clock gene Per1 and other clock-related genes. • The transcriptional effects matched the window of fetal clock sensitivity to DEX.

Source: Biomedicine & Pharmacotherapy

DOI: 10.1016/j.biopha.2026.119486

Authors: Martin Sládek, Pedro Cadenato, Kateryna Semenovykh, Pavel Houdek, Alena Sumová

Institutions: Czech Academy of Sciences, Czech Academy of Sciences, Institute of Physiology

Language: English

Topic: Circadian rhythm and melatonin

Subfield: Endocrine and Autonomic Systems

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,610