Hypoxia Induces Apoptosis through HIF-1α Signaling Pathway in Human Uterosacral Ligaments of Pelvic Organ Prolapse

Abstract

The purpose of this study is to evaluate the expression of hypoxia-inducible factor-1α (HIF-1α) in women uterosacral ligament tissues with pelvic organ prolapse and women with normal uterine support structures and illuminate its relationship with apoptosis. Samples were collected from 38 women with pelvic organ prolapse and 31 age matched controls. The expression levels of HIF-1α and BNIP3 in the uterosacral ligaments were measured using immunohistochemistry, qRT-PCR, and Western blot. To assess apoptosis we performed TUNEL assay and Western blot analyses. Lastly, the short form of the Pelvic Floor Impact Questionnaire-7 (PFIQ-7) was used to evaluate prognosis of surgical patients and twenty patients finished the follow-up. The expressions of HIF-1α and BNIP3 in the uterosacral ligaments were significantly higher in patients with pelvic organ prolapse than in control group. Pearson’s correlation test revealed significant positive correlations between HIF-1α and apoptosis index. Similarly, Western blot analysis showed the expression of proapoptosis proteins (Bax and Bad), Cytochrome-c, cleaved caspase-3, and caspase-9 in patients with pelvic organ prolapse was upregulated. The PFIQ-7 scores were higher in HIF-1α positive group than in the negative group. Hypoxia may contribute to the pathological process of pelvic organ prolapse by increasing apoptosis via activating HIF-1α signaling pathway.