Association between HIF‐1α, BNIP3, and autophagy in the chorionic villi of missed abortion

Abstract Aim To investigate the expression of autophagy mediated by the hypoxia‐inducible factor 1α (HIF‐1α)/BNIP3 signaling pathway in villus tissues of missed abortion and HTR‐8/SVneo cells and to elucidate the association of HIF‐1α and BNIP3 in autophagy of missed abortion. Methods Villus tissues from 30 healthy women with induced abortion and 35 patients with missed abortion were collected, and HTR‐8/SVneo cells were cultured under hypoxia and transfected with HIF‐1α‐siRNA. Real‐time polymerase chain reaction was utilized to measure the mRNA levels of HIF‐1α and BNIP3; Western blotting was performed to determine the protein levels of HIF‐1α, BNIP3, LC3 II/I, and Beclin 1 in villus tissues and HTR‐8/SVneo cells. Cellular invasion activity was detected by transwell matrigel assay. The level of autophagy was confirmed by transmission electron microscopy of autophagosome formation. Results The mRNA levels of HIF‐1α and BNIP3 were significantly lower in the missed abortion villi than in the induced abortion samples. The protein levels of HIF‐1α, BNIP3, Beclin 1, and LC3II/I were significantly decreased in villus tissues from missed abortion, and autophagosomes were significantly decreased in villus tissues from missed abortion. Under hypoxia, the mRNA expression of HIF‐1α and BNIP3 was inhibited after silencing HIF‐1α by RNAi, while the protein expression of HIF‐1α, BNIP3, Beclin1, and LC3II/I was significantly downregulated. The number of invading cells was significantly decreased, and autophagosomes were significantly decreased after silencing HIF‐1α by RNAi in HTR‐8/SVneo cells. Conclusions Autophagy mediated by the HIF‐1α/BNIP3 signaling pathway in villous trophoblast cells may be associated with the progression and development of missed abortion.