title: [Mechanism of hypoxia inducing factor-1α in low endometrial receptivity].
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 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.
  
  
  RESULTS
  (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.
  
  
  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.
authors: Reproduction Center of Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
authors: Bu-fang
authors: BF
authors: Xu
authors: Xiao-xi
authors: XX
authors: Sun
authors: Yun
authors: Y
authors: Feng
authors: Ai-Jun
authors: AJ
authors: Zhang
authors: Li-nan
authors: LN
authors: Cheng
mesh_terms: D000026:Abortion, Habitual / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D017209:Apoptosis; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D000074049:Cytokine TWEAK; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000074049:Cytokine TWEAK; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; C109743:TNFSF12 protein, human; D048069:Tumor Necrosis Factors