Mechanism of hypoxia inducing factor-1α in low endometrial receptivity

Abstract

To study the mechanism of hypoxia inducing factor-1α (HIF-1α) pathway in establishment of hypoxia inducing low endometrial receptivity. 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 cytometry. 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. (1) On different 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 ± 0.020 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. 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.