Mechanism of hypoxia inducing factor-1α in low endometrial receptivity / 中华妇产科杂志

ABSTRACT

Objective To study the mechanism of hypoxia inducing factor-1α(HIF-1α)pathway in establishment of hypoxia inducing low endometrial receptivity.Methods RL95-2 cell lines.the ideal model of study ER,were cultured in hypoxia condition induced by CoCl2,and the expression of mRNA and protein of HIF-1α and tumor necrosis factor like weak inducer of apoptosis(TWEAK)were measured by reverse transcription-PCR and western blot. The apoptosis rate was analyzed by flow eytometry.Then the mechanism confirmed by comparing the two factors in endometrium and the ultra-appearance of inflammatory reaction and apoptosis between recurrent spontaneous abortion women and control women.Results (1)On difierent time point(0,12,24,48 hour),mRNA expression of HIF-1α were 0.272±0.010,0.354±0.020,0.591±0.020.0.890±0.020,while the expression of TWEAK were 0.104±0.010,0.510±0.020,1.021±0. 020, 1. 237 +0. 040, respectively, the expression level between 12, 24, 48 and 0 hour all showed significant differences (P＜0. 05 ). (2) Protein expression of HIF-1α were 0. 853 +0. 010, 0. 931 ±0. 030,1. 124±0.010, 1.317±0.0 20 respectively, while was 0.042±0.010, 0.091 ±0.010, 0. 131±0.020,0. 205 ±0. 030 in TWEAK expression, the different level were statistically significant ( P＜0. 05 ). ( 3 )With longer culture under hypoxia, the cell apoptosis rate increased obviously. The apoptosis rate of each time point were ( 3.2±1.4 ) %, ( 16. 2 ±3.2 ) %, ( 26. 3±3.5 ) %, ( 31.8±3.5 )%, the differences between 12, 24, 48 and 0 hour had significance (P ＜0. 05). (4) The positive rate of HIF-1α stained in epithelium cells and stroma cells of test group were 32. 3%, 8.4% and 16. 7%, 7. 3% in control group. The positive rate of TWEAK were 28. 3%, 3.9% in recurrent spontaneous abortion group and 11.6%, 2. 7% in control group ( P ＜0. 05 ). The ultra-appearance of inflammatory cell infiltrated and apoptosis were obvious in test group. Conclusions Cell inflammation reaction and apoptosis induced by HIF-1α pathway may participate the mechanism of hypoxia inducing low endometrial receptivity. HIF-1α might become a novel target for improving poor endometrial receptivity.