报告题目：The disruption of the circadian clock contributes to endometrial remodeling during early pregnancy

　　报告人：Assistant Professor KeishiroIsayama（日本山口大学谏山慧士郎助理教授）

　　报告时间：2018年12月9日上午9:30-12:00

　　报告地点：北校区动物医学院4号教学楼4143会议室

　　摘要：

　　The circadian clock is generated by interlocked transcriptional/translational loop of core clock genes/proteins. The core clock genes/proteins also regulate the rhythmic expression of numerous downstream genes, which are called clock-controlled genes (CCGs), through binding to their transcriptional promoters. Therefore, it is speculated that the circadian clock also has some roles in the uterine function by mediating CCGs, but it was not well understood. Interestingly, in rat and human, it were reported that the expression of Per2, one of clock genes, is rhythmic in the uterus during implantation, whereas the rhythmic expression is disrupted during decidualization1. This event was thought to be the key to understanding the role of clock in the uterus during early pregnancy. Here, the present study was performed to reveal the CCGs involved in early pregnancy and the effect of disrupted circadian clock on the CCGs expression during early pregnancy. To explore the putative CCGs in the uterus, DNA microarray were performed using cultured endometrial stromal cells derived from pregnant rats at implantation stage. In consequence, 11 implantation-related genes and 24 placentation-related genes showed diurnal changes in gene expression level2. In screened putative CCGs, we focused on prostaglandin G/H synthetase 2 (Ptgs2), which is a critical factor during early pregnancy. ChIP and antagonist assay revealed REV-ERBα, a heme receptor belonging to core clock proteins, directly inhibit Ptgs2 transcription. In addition, PTGS2 were up-regulated at mRNA and protein level in decidualizing endometrium, whereas REV-ERBα were down-regulated. These results suggested that the disruption of circadian clock, especially the down-regulation of Rev-erbα results in the enhancement of Ptgs2 transcription in the endometrial decidualization3. This finding may contribute to our understanding of the mechanism regulating endometrial remodeling during early pregnancy. 

　　报告人简介：

　　谏山慧士郎助理教授，2015年毕业于日本九州大学，获农学博士学位。2016年至今在日本山口大学生物医学研究所任助理教授职位。谏山助理教授是日本生殖生物钟研究领域的青年科学家，其研究主要集中于生物钟调控生殖功能机制研究。截至目前，谏山慧士郎助理教授共在American Journal of Physiology-Cell Physiology、 American Journal of Physiology-Endocrinology and Metabolism、Frontiers in Endocrinology、Reproductive Toxicology、 Journal of Reproduction and Development.等国际著名术期刊发表学术论文5余篇。

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　　动物医学院

　　2018年12月5日

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