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

Xinrui Zhao,Peishu Liu,Congcong Ma,Rui Li,Jing Xue,Lidong Liu

doi:10.1155/2017/8316094

Xinrui Zhao, Peishu Liu + Show 4 more

Open Access

https://doi.org/10.1155/2017/8316094

Copy DOI

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.

Highlights

Pelvic organ prolapse (POP), the fall of the female pelvic organs into or through the vagina, is a common and costly condition in elderly women [1]
We found that the immunoreactivity of hypoxia-inducible factor-1α (HIF-1α) in uterosacral ligaments (USLs) tissues of the POP group was significantly higher than the control group (1.477 ± 0.779, versus 2.668 ± 1.542, resp.; P < 0.01)
QRT-PCR and Western blot analysis revealed the expression of HIF-1α and BNIP3 was increased in the level of mRNA and protein, respectively (Figures 1(b)–1(d))

Summary

Introduction

Pelvic organ prolapse (POP), the fall of the female pelvic organs (vagina, uterus, bladder, and/or rectum) into or through the vagina, is a common and costly condition in elderly women [1]. The estimated lifetime risk of surgery for POP is 12.6% by the age of 80 years [2]. Several risk factors for POP such as advancing age, vaginal childbirth, increasing body-mass index, family history of POP, and chronic intra-abdominal pressure are well established [5,6,7], the underlying molecular mechanism remains unknown. Pelvic organ support is mainly provided by the connective tissues (endopelvic fascia and ligaments) and the levator ani muscles [5]. Pelvic trauma related childbirth; pelvic surgeries; or even chronic mechanical stress may increase apoptosis and lead to abnormal tissue remodeling. Some studies have proposed the hypothesis that hypoxia may cause the apoptosis of the USLs [16]

Objectives

Methods

Results