Title: The disruption of the circadian clock contributes to endometrial remodeling during early pregnancy

Speaker:Assistant ProfessorKeishiroIsayama (Institute of Life Science and Medicine, Science Research Center, Organization for Research Initiatives, Yamaguchi University, Japan)

Time: 9:30-12:00 am, December 9th, 2018

Venue: Room No. 4143, Building 4, North Campus, College of Veterinary Medicine

Abstract:

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. 

A Brief Introduction to the Speaker:

Dr. KeishiroIsayama graduated and acquired his Ph.D degree from Kyushu University, Japan in 2015. From 2016 to the present, He was an assistant professor of Institute of Life Science and Medicine, Science Research Center, Organization for Research Initiatives, Yamaguchi University, Japan.Dr. Isayama is a young scientist of chronobiology in reproduction, whose research interest focusing on Chronobiology (circadian rhythm), reproductive physiology and endocrinology. Dr. Isayama published more than5 papers in international academic journals, such as American Journal of Physiology-Cell Physiology, American Journal of Physiology-Endocrinology and Metabolism, Frontiers in Endocrinology, Reproductive Toxicology, Journal of Reproduction and Development.

All the teachers and students are welcome to attend this seminar.

College of Veterinary Medicine

December 5th, 2018