Fetal daily rhythms develop during pregnancy and entrain to the maternal circadian system

Abstract

AbstractCircadian rhythms in gene expression and hormones are ubiquitous across species and differentiated cell types. This study aimed to determine when daily rhythms begin in the fetus and synchronize to the mother. We developed methods to monitor the expression of fetal PERIOD2 (PER2), a core circadian clock protein, in mice longitudinally from embryonic day (E)8.5 to E17.5 throughin uterobioluminescence imaging. We found that embryonic PER2 expression increased rapidly throughout pregnancy and exhibited day-night rhythms from the start of our recordings at E8.5. The daily peak time of PER2 varied between pregnancies until it reliably peaked at night and synchronized to the mother starting around E15.5. Loss of fetal circadian rhythms associated with pregnancies that ultimately failed. Because maternal glucocorticoids have been implicated in fetal development and synchronizing circadian tissues, we tested their sufficiency to shift fetal daily rhythms in utero. Daily glucocorticoids injections over five days of late pregnancy advanced fetal PER2 rhythmsin uteroand blocking glucocorticoid signalingin vitroreduced PER2 synchrony between the maternal and fetal placenta by ∼40%. We conclude that fetal daily rhythms arise early in pregnancy and then synchronize with the maternal rhythm prior to birth depending, in part, on glucocorticoid signaling.