Fig. 7

Schematic diagram showing the roles of circadian rhythm in decidualization and pregnancy. The expression of Rev-erbα depends on normal sleep, which is essential for pregnant establishment and maintenance. Rev-erbα, as a transcription factor, directly repressed IL-6/IL-6R expression via binding their promoter region. IL-6/IL-6R axis could suppress the expression of C/EBPβ and its target IGFBP1, the marker of decidualization, by inhibiting PR expression. Sleep disturbance suppressed the expression of Rev-erbα in ESCs, which induced deficient decidualization via the disequilibrated IL-6/IL-6R-PR-C/EBPβ signal axis. Administration with Rev-erbα agonist SR9009 and IL-6 neutralized antibody could both alleviate the defective decidualization and adverse pregnancy outcomes induced by sleep disturbance.