生殖医学杂志2018，Vol.27Issue(5)：416-421,6.DOI:10.3969/j.issn.1004-3845.2018.05.005
月经发生中低氧诱导因子-1A对VEGF的调节
The regulation of VEGF expression by hypoxia-inducible factor-1A during menstruation
摘要
Abstract
Objective:To investigate the regulation of HIF1A(hypoxia-inducible factor) on the expression of vascular endothelial growth factor(VEGF) protein and mRNA in mouse menstrual models and in vitro cultured human decidualized endometrial stromal cells to explore the role of HIF1A in menstruation.Methods:The physiological menstruation model of progesterone withdrawal in mouse was established and ChIP assay was used to detect the direct regulation of HIF1A on Vegf.HIF1A inhibitor methoxyestradiol(2ME) was used to intervene in the menstrual-like model and detect the expression of HIF1A and VEGF protein.Human decidualized endometrial stromal cells were prepared in vitro to simulate menstruation.The expression of VEGF mRNA was detected after knockdown of HIF1A by siRNA.Results:In the mouse menstrual-like model at 0h after progesterone withdrawal,the relative percentage of HIF1A-conjugated Vegf promoter was lower,then it gradually increased at 8h and 12h,peaked at 12 h(P＜0.05).At 16h,the relative percentage of HIF1A-conjugated Vegf promoter rapidly decreased and increased slightly at 24 h,but only about 1/2 of the peak level at 12h.2ME inhibited the entry of HIF1A into the nucleus and significantly decreased VEGF expression(P＜0.05).In human decidualized endometrial stromal cells,progesterone withdrawal significantly up-regulated the expression of HIF1A and VEGF mRNA.Knockdown of HIF1A significantly inhibited the expression of VEGF mRNA (P＜0.01).Conclusions:In the onset of menstruation after the progesterone withdrawal,HIF1A is translocated to the nucleus and transcription factor function activated,and the expression of the downstream regulatory gene VEGF is directly initiated.关键词
HIF1A/VEGF/小鼠月经样模型/子宫内膜基质细胞Key words
VEGF/HIF1A/Mouse model of menstruation/Human endometrial stromal cell引用本文复制引用
郭士格,陈西华,南楠,尹德东,周芳,王树芳,刘建兵,贺斌,王介东,徐祥波..月经发生中低氧诱导因子-1A对VEGF的调节[J].生殖医学杂志,2018,27(5):416-421,6.基金项目
国家自然科学基金面上项目(81571410) （81571410）
北京市自然科学基金(7152115) （7152115）
