HIF1A Regulates The Effect Of CXCR4 On The Disintegration Of The Endometrium During Menstruation

Menstruation is a periodic endometrial shedding bleeding characteristic of humans and higher primates and a few remaining placental animals.Abnormal endometrial bleeding manifests as menorrhagia,too little or irreguLar bleeding.This is an important problem that plagues the practice of clinical and family planning in obstetrics and gynecology,and has become an important factor affecting women's reproductive health and quality of life[1].The analysis of physiological endometrial periodic disintegration hemorrhage mechanism is the key to understanding abnormal bleeding and finding treatment strategies,and has a significant impact on female reproductive health.At 1940s,Markee used a rhesus monkey endometrial explant model to observe that the endometrial spiral artery contracted for about 24 hours before menstruation.It is specuLated that the key factor leading to disintegration of the endometrium is tissue ischemia and hypoxia[2].However,due to limitations in experimental conditions and lack of animal models,menstrual research has been slow.In the 1980s,mice were first brought into the research field of the menstrual mechanism to break the bottleneck[3].In the early 20th century,the mouse-like menstrual model has been optimized[4].In 2007,the research team established a mouse model of pharmacological P4 withdrawal menstruation,based on the menstrual-like mouse model based on the in-depth study of the mechanism of menstruation and achieved certain resuLts.Based on the resuLts of the previous studies,this study investigated the progesterone withdrawal and Hypoxia inducible based on the physiological menstruation-like progesterone withdrawal model and human decidualization of endometrial stromal cells to simuLate menstruation.The reguLation of factor-1,HIF1 A)and CXC chemokine receptor type 4(CXCR4)during menstruation.The main resuLts are as follows:In the mouse menstrual-like model and in vitro cuLtured human decidualized endometrial stromal cells that mimic menses,progesterone withdrawal resuLted in the up-reguLation of Hif1a mRNA,and the expression of HIF1Ain the nucleus and cytoplasm increased,ie HIF1A The function is activated.After withdrawal of progesterone,both Cxcr4 mRNA expression and protein expression were increased.In the disintegration period(0-24 h)of the mouse menstrual-like model,the localization of HIF1 Aand CXCR4 proteins was correlated.In the disintegration phase of the menstrual-like model in mice,after inhibiting HIF1A,the expression of Cxcr4 mRNA and the expression of CXCR4 protein in the endometrium were both significantly reduced.At the same time,the disintegration of the endometrium was inhibited.After inhibiting CXCR4,disintegration of the endometrium was inhibited.This resuLt confirms that HIF1A and CXCR4 play an important role in disintegration of the endometrium,and P4 withdrawal can up-reguLate the expression of Cxcr4 gene through HIF1A.In human decidualized human endometrial stromal cells,the expression of CXCR4 mRNA was up-reguLated after withdrawal of the mimetic hormone,whereas the expression of CXCR4 mRNA was suppressed after knockdown of HIF1A.This resuLt was confirmed at the celluLar level.After the withdrawal of P4,the expression of CXCR4 mRNA increased,and the expression of CXCR4 mRNA was significantly inhibited after HIF1A knockdown.Therefore,HIF1AreguLates the expression of CXCR4.