title: Removal of Rev-erbα inhibition contributes to the prostaglandin G/H synthase 2 expression in rat endometrial stromal cells.
abstract: The rhythmic expression of clock genes in the uterus is attenuated during decidualization. This study focused on Ptgs2, which is essential for decidualization, as a putative clock-controlled gene, and aimed to reveal the functions of clock genes in relation to Ptgs2 during decidualization. We compared the transcript levels of clock genes in the rat uterus on days 4.5 (D4.5) and 6.5 of pregnancy. The transcript levels of clock genes (Per2, Bmal1, Rorα, and Rev-erbα) had decreased at implantation sites on day 6.5 (D6.5e) compared with those on D4.5, whereas Ptgs2 transcripts had increased on D6.5e. Similar observations of Rev-erbα and Ptgs2 were also obtained in the endometrium on D6.5e by immunohistochemistry. In the decidual cells induced by medroxyprogesterone and 2-O-dibutyryl-cAMP, the rhythmic expression levels of clock genes were attenuated, whereas Ptgs2 transcription was induced. These results indicate that decidualization causes the attenuation of clock genes and the induction of Ptgs2. Furthermore, in the experiment of Bmal1 siRNA, the rhythmic expression of clock genes and Ptgs2 was attenuated by the siRNA. Transcript levels of Ptgs2 and prostaglandin (PG)E₂ production were increased by treatment with the Rev-erbα antagonist, suggesting the contribution of the nuclear receptor Rev-erbα to Ptgs2 expression. Moreover, Rev-erbα knockdown enhanced the induction of Ptgs2 transcription and PGE₂ production by forskolin. Chromatin immunoprecipitation-PCR analysis revealed that Rev-erbα could directly bind to a proximal RORE site of Ptgs2. Collectively, this study demonstrates that the attenuation of the circadian clock, especially its core component Rev-erbα, contributes to the induction of Ptgs2 during decidualization.
authors: Department of Animal and Marine Bioresource Sciences, Graduate School of Agriculture, Kyushu University, Fukuoka, Japan;
authors: Keishiro
authors: K
authors: Isayama
authors: Department of Animal and Marine Bioresource Sciences, Graduate School of Agriculture, Kyushu University, Fukuoka, Japan;
authors: Lijia
authors: L
authors: Zhao
authors: Department of Animal and Marine Bioresource Sciences, Graduate School of Agriculture, Kyushu University, Fukuoka, Japan;
authors: Huatao
authors: http://orcid.org/0000-0002-3800-5013
authors: H
authors: Chen
authors: Department of Animal and Marine Bioresource Sciences, Graduate School of Agriculture, Kyushu University, Fukuoka, Japan;
authors: Nobuhiko
authors: N
authors: Yamauchi
authors: Department of Anatomy and Neurobiology, Kinki University School of Medicine, Osaka, Japan; and.
authors: Yasufumi
authors: Y
authors: Shigeyoshi
authors: Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors: Seiichi
authors: S
authors: Hashimoto
authors: Department of Animal and Marine Bioresource Sciences, Graduate School of Agriculture, Kyushu University, Fukuoka, Japan; mhattori@agr.kyushu-u.ac.jp ma_hattori@kyudai.jp.
authors: Masa-aki
authors: MA
authors: Hattori
mesh_terms: D020121:5' Untranslated Regions; D056930:ARNTL Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D057906:Circadian Clocks; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D004717:Endometrium / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000235:genetics / Q000378:metabolism; D010929:Placentation; D011247:Pregnancy; D011388:Prolactin / Q000031:analogs & derivatives / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D051381:Rats; D055647:Rats, Transgenic; D020218:Response Elements; D017154:Stromal Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*
chemical_list: D020121:5' Untranslated Regions; D056930:ARNTL Transcription Factors; C000598703:Arntl protein, rat; C498263:Nr1d1 protein, rat; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; C079559:Prl8a2 protein, rat; D034741:RNA, Small Interfering; C000598704:Roralpha protein, rat; D011388:Prolactin; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat
keywords: Rev-erbα; chromatin immunoprecipitation; circadian clock; decidualization; prostaglandin