Prostaglandin G/H synthase 2 (PTGS2) is a rate-limiting enzyme in prostaglandin synthesis. The present study assessed the role of the uterine circadian clock ontranscription in response to steroid hormones during early pregnancy. We demonstrated that the core clock genes (,,, and),, andand their encoded proteins, have rhythmic expression in the mouse uterus fromto() of pregnancy. Progesterone (P) treatment of cultured uterus endometrial stromal cells (UESCs) isolated fromreporter gene knock-in mice on D4 induced a phase shift inoscillations. This P-induced phase shift ofoscillations was significantly attenuated by the Pantagonist RU486. Additionally, the amplitude ofoscillations was increased by estradiol (E) treatment in the presence of P. Consistently, the mRNA levels of clock genes (and),, andwere markedly increased by Etreatment of UESCs in the presence of P. Treatment with Ealso promoted prostaglandin E(PGE) synthesis by UESCs. Depletion ofin UESCs by small-interfering RNA (siRNA) decreased the transcript levels of clock genes (and),, andcompared with nonsilencing siRNA treatment.knockdown also inhibited PGEsynthesis. Moreover, the mRNA expression levels of clock genes (and),, and, and their respective proteins were significantly decreased in the uterus ofmice. Thus, these data suggest thatin mice promotes PGEsynthesis by upregulatingin response to increases in Eon D4 of pregnancy.Rhythmic expression of Bmal1 and Ptgs2 was observed in the uterus isolated fromof pregnant mice. Eincreased the expression of Bmal1 and Ptg2 in UESCs isolated from mice on D4. The expression of Ptgs2 was significantly decreased in Bmal1-siRNA treated UESCs.knockdown also inhibited PGEsynthesis. Thus, these data suggest that Bmal1 in mice promotes PGEsynthesis by upregulating Ptgs2 in response to increases in Eon D4 of pregnancy. Ptgs2Bmal1Per2Nr1d1Dbp Vegf Ptgs2, days 3.5 4.5D3.5-4.5mPer2Luciferase PER2::LUCIFERASE PER2::LUCIFERASE PER2::LUCIFERASE Bmal1Per2Vegf Ptgs2Bmal1Nr1d1Dbp Vegf Ptgs2Bmal1Nr1d1Dbp Vegf Ptgs2Bmal1 -/-Bmal1Ptgs2D3.5-4.5Bmal1 4 4 4 2 4 2 4 2 2 2 2 2 2 2 2 2 2NEW & NOTEWORTHY
