Executive Summary : | "Heavy Menstrual Bleeding (HMB) is a gynecological disorder characterized by menstrual blood loss exceeding 80ml or bleeding 7 days per cycle. It is a major cause of hysterectomy in women of reproductive age and significantly affects their quality of life and productivity. The endometrium, a hormone-responsive organ, undergoes repair during the end of each menstrual cycle, which is initiated without steroid hormone. However, inefficient or dysregulated endometrial repair is one of the causes of HMB. The fall in progesterone levels at the end of the menstrual cycle leads to vasoconstriction, ischemia, and hypoxic microenvironment, eliciting numerous inflammatory pathways for efficient endometrial repair. It remains to identify the regulators of inflammatory pathways that regulate immune cell dynamics during endometrium repair. A laboratory study found that extracellular released HMGB1 (High Mobility Group B 1 protein) in uterine fluid during proliferative and secretary phases of the menstrual cycle in humans and increased levels during repair phases of estrus cycle and experimentally induced rat model of endometrial breakdown and repair. Inhibition of HMGB1 by pharmacological inhibitor (glycyrrhizin) and chemical RAGE inhibitor (FPS-ZM1) alone or in combination delayed endometrial repair in the rat model of endometrial breakdown and repair.
The aim of this study is to characterize the immune cells repertoire downstream of the HMGB1-RAGE axis by inhibiting HMGB1-RAGE signaling in rat model endometrial breakdown and repair. Understanding the role of HMGB1-RAGE axis in activating immune cells repertoire could help control inflammation, tissue repair, and clearance of damage cells during endometrium breakdown and repair, potentially revealing the causes of heavy menstrual bleeding in women." |