Development and Entrainment of the Fetal Clock in the Suprachiasmatic Nuclei: The Role of Glucocorticoids

Mar 12, 2019Journal of biological rhythms

Development and Synchronization of the Baby's Internal Clock in the Brain's Timekeeping Center: The Role of Stress Hormones

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

The maternal placenta contains an autonomous circadian clock that regulates glucocorticoid passage to the fetal suprachiasmatic nucleus (SCN).

The fetal SCN clock may respond to changes in glucocorticoid levels.
Maternal glucocorticoids are capable of reaching the fetal SCN through the placenta.
Cultured hypothalamic explants from fetal rodents show spontaneous rhythmicity that varies among fetuses.
Dexamethasone accelerates the development of rhythmicity in fetal SCN explants.
Dexamethasone treatment at embryonic day 17 induces phase shifts in SCN rhythms, which are blocked by a glucocorticoid receptor antagonist.

AI simplified

The adult circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus is resilient to glucocorticoids (GCs). The fetal rodent SCN resembles that of the adult in its organization of GC-sensitive peripheral tissues. We tested the hypothesis that the fetal SCN clock is sensitive to changes in GC levels. Maternal GCs must pass through the placenta to reach the fetal SCN. We show that the maternal but not the fetal part of the placenta harbors the autonomous circadian clock, which is reset by dexamethasone (DEX) and rhythmically expresses Hsd11b2. The results suggest the presence of a mechanism for rhythmic GC passage through the placental barrier, which is adjusted according to actual GC levels. GC receptors are expressed rhythmically in the laser-dissected fetal SCN samples. We demonstrate that hypothalamic explants containing the SCN of the mPer2mouse prepared at embryonic day (E)15 spontaneously develop rhythmicity within several days of culture, with dynamics varying among fetuses from the same litter. Culturing these explants in media enriched with DEX accelerates the development. At E17, treatment of the explants with DEX induces phase advances and phase delays of the rhythms depending on the timing of treatments, and the shifts are completely blocked by the GC receptor antagonist, mifepristone. The DEX-induced phase-response curve differs from that induced by the vehicle. The fetal SCN is sensitive to GCs in vivo because DEX administration to pregnant rats acutely downregulates c-fos expression specifically in the laser-dissected fetal SCN. Our results provide evidence that the rodent fetal SCN clock may respond to changes in GC levels. Luc

Full Text

Full text is available at the source.

View full text (PDF) ↗View full text (XML) ↗View full text ↗

Development and Entrainment of the Fetal Clock in the Suprachiasmatic Nuclei: The Role of Glucocorticoids

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief