Fetoplacental circadian rhythms develop and then synchronize to the mother <i>in utero</i>

Circadian rhythms in gene expression and hormones are ubiquitous across species and differentiated cell types, yet their developmental origins remain poorly understood. This study aimed to determine if daily rhythms can be detected <i>in utero</i> and if they synchronize to the mother. We developed methods to longitudinally monitor PERIOD2 (PER2), a core circadian clock protein, from embryonic day (E)8.5 to E17.5 by restricting PER2::LUCIFERASE (PER2::LUC) expression to the mouse fetoplacental unit (fetus and fetal-derived tissues). <i>In utero</i> fetoplacental bioluminescence imaging showed that PER2 levels rose exponentially during pregnancy, with variable daily peak times that stabilized to dusk by E15.5. Interestingly, pregnancies that did not exhibit daily <i>in utero</i> PER2 variation were more likely to fail. Because maternal glucocorticoids have been implicated in fetal development and synchronizing other circadian tissues, we tested its capability to shift fetoplacental PER2 rhythms <i>in utero</i>. Daily subcutaneous glucocorticoid injections over five days of late pregnancy phase-dependently shifted the fetoplacental PER2 rhythms <i>in utero</i>. Blocking glucocorticoid signaling <i>in vitro</i> reduced synchrony between maternal and fetal placenta by ~40%. We conclude that <i>in utero</i> daily rhythms gradually develop and synchronize with the mother prior to birth, potentially through glucocorticoid signaling.