Profiling of circadian genes expressed in the uterus endometrial stromal cells of pregnant rats as revealed by DNA microarray coupled with RNA interference

Tasaki, Hirotaka; Zhao, Lijia; Isayama, Keishiro; Chen, Huatao; Yamauchi, Nobuhiko; Shigeyoshi, Yasufumi; Hashimoto, Seiichi; Hattori, Masa Aki

doi:10.3389/fendo.2013.00082

Cited by 22 publications

(14 citation statements)

References 55 publications

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“…Moreover, our previous data obtained from a DNA microarray in UESCs isolated from day 4.5 of rat pregnancy (49) suggested that the expression level of the Ptgs2 transcript is rhythmic. In the present study, Ptgs2 expressions were affected by Bmal1-siRNA (Fig.…”

Section: Discussionmentioning

confidence: 91%

Removal of Rev-erbα inhibition contributes to the prostaglandin G/H synthase 2 expression in rat endometrial stromal cells

Isayama

Zhao

Chen

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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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.

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Section: Discussionmentioning

confidence: 91%

Removal of Rev-erbα inhibition contributes to the prostaglandin G/H synthase 2 expression in rat endometrial stromal cells

Isayama

Zhao

Chen

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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“…In addition, aging Per1 m/m /Per2 m/m double mutation mice have a significantly reduced number of ovarian follicles, displaying a decrease in female fertility starting approximately at 20 weeks and have significantly fewer pups born from 32 weeks old and onwards [77]. The Per2 oscillation was increased in uteri endometrial stromal cells (UESCs) during implantation, and decreased during differentiation [78]. Cellular differentiation interferes with the circadian clockwork in differentiating cells.…”

Section: Per1 1 2 Andmentioning

confidence: 99%

Circadian Clock, Time-Restricted Feeding and Reproduction

Pan

Taylor

Cohen

et al. 2020

IJMS

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The goal of this review was to seek a better understanding of the function and differential expression of circadian clock genes during the reproductive process. Through a discussion of how the circadian clock is involved in these steps, the identification of new clinical targets for sleep disorder-related diseases, such as reproductive failure, will be elucidated. Here, we focus on recent research findings regarding circadian clock regulation within the reproductive system, shedding new light on circadian rhythm-related problems in women. Discussions on the roles that circadian clock plays in these reproductive processes will help identify new clinical targets for such sleep disorder-related diseases.

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“…To gain insight into the cellular clocks of UESCs and the circadian regulation of physiology, the global expression of the Bmp genes, which are vital for decidualized uterus function, were analyzed by DNA microarray (58). The results are shown in Fig.…”

Section: Expression Levels Of the Bmp Genes In Uescs And Whole Uterusmentioning

confidence: 99%

Inhibitory role of REV-ERBα in the expression of bone morphogenetic protein gene family in rat uterus endometrium stromal cells

Tasaki

Zhao

Isayama

et al. 2015

American Journal of Physiology-Cell Physiology

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Uterus circadian rhythms have been implicated in the gestation processes of mammals through entraining of the clock proteins to numerous downstream genes. Bone morphogenetic proteins (BMPs), having clock-controlled regulatory sites in their gene promoters, are expressed in the uterus during decidualization, but the regulation of the Bmp gene expression is poorly understood. The present study was designed to dissect the physiological roles of the uterus oscillators in the Bmp expression using the uterus endometrial stromal cells (UESCs) isolated from Per2-dLuc transgenic rats on day 4.5 of gestation. The in vitro decidualization of UESCs was induced by medroxyprogesterone acetate and 2-O-dibutyryl cAMP. A significant decline of Per2-dLuc bioluminescence activity was induced in decidual cells, and concomitantly, the expression of canonical clock genes was downregulated. Conversely, the expression of the core Bmp genes Bmp2, Bmp4, Bmp6, and Bmp7 was upregulated. In UESCs transfected with Bmal1-specific siRNA, in which Rev-erbα expression was downregulated, Bmp genes, such as Bmp2, Bmp4, and Bmp6 were upregulated. However, Bmp1, Bmp7, and Bmp8a were not significantly affected by Bmal1 silencing. The expression of all Bmp genes was enhanced after treatment with the REV-ERBα antagonist (SR8278), although their rhythmic profiles were differed from each other. The binding of REV-ERBα to the proximal regions of the Bmp2 and Bmp4 promoters was revealed by chromatin immunoprecipitation-PCR analysis. Collectively, these results indicate that the Bmp genes are upregulated by the attenuation of the cellular circadian clock; in particular, its core component REV-ERBα functions as a transcriptional silencer in the Bmp gene family.

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Profiling of circadian genes expressed in the uterus endometrial stromal cells of pregnant rats as revealed by DNA microarray coupled with RNA interference

Cited by 22 publications

References 55 publications

Removal of Rev-erbα inhibition contributes to the prostaglandin G/H synthase 2 expression in rat endometrial stromal cells

Removal of Rev-erbα inhibition contributes to the prostaglandin G/H synthase 2 expression in rat endometrial stromal cells

Circadian Clock, Time-Restricted Feeding and Reproduction

Inhibitory role of REV-ERBα in the expression of bone morphogenetic protein gene family in rat uterus endometrium stromal cells

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