Koc Onder, Ozdemirici Safak, Acet Mustafa, Soyturk Ummugulsum, Aydin Suleyman
a Department of Obstetrics and Gynecology , Memorial Ankara Hospital , Ankara , Turkey.
b Department of Obstetrics and Gynecology , Etlik Zubeyde Hanim Women's Health Teaching and Research Hospital , Ankara , Turkey.
J Obstet Gynaecol. 2017 Oct;37(7):924-930. doi: 10.1080/01443615.2017.1315563. Epub 2017 Jun 15.
The aim of this study was to investigate whether the expression levels of endometrial NFκB p65 differ between normal weight and overweight PCOS women and to compare them with BMI-matched control subjects without PCOS. The study group comprised 20 normal weight (BMI: 18.5-24.9 kg/m) and 15 overweight PCOS women (BMI: 25-29.9 kg/m) with infertility. Healthy fertile women without PCOS were recruited as the control group. The patients in the normal weight PCOS group and control group were age and BMI-matched. Endometrial samples were obtained during the mid-luteal phase for immunohistochemical staining. The H-Score method was used to evaluate NF-κB p65 (Rel A) expression. Both normal and overweight PCOS women demonstrated significantly higher endometrial NF-κB p65 expression than the women without PCOS. The H-scores of endometrial NF-κB p65 expression were similar in both groups of PCOS women. NF-κB p65 was positively correlated with serum insulin, HOMA-IR and total testosterone levels in PCOS women. By leading to pathological inflammation, an increase in NF-κB p65 expression in the endometrium of normal and overweight PCOS women may contribute to PCOS-related subfertility. Impact statement What is already known on this subject: Although the pathogenesis of PCOS has not yet been clarified, low-grade chronic inflammation is gradually being established as an important pathogenetic factor. Increased levels of inflammatory cytokines such as IL-6 and TNF-α have been reported in women with PCOS. Causes of pathological endometrial inflammation may arise from either a local endometrial disease or linked to diseases which are located in a distant reproductive tissue. Nevertheless, possible role of endometrial NF-κB, basic cellular regulatory of inflammation, in the pathophysiology of PCOS related implantation defect has not been elucidated yet. What do the results of this study add: This study provides first and novel insights into the relationship between PCOS related infertility and pathological endometrial inflammation. We demonstrated that there is a close association between PCOS and pathological endometrial inflammation. Moreover, we clearly showed that pathological endometrial inflammation occurs in both normal and overweight women with PCOS. Further, endometrial NF-κB p65 (Rel A) expression were found to be positively correlated with serum insulin levels and hyperandrogenism in overweight PCOS women. What are the implications of these findings for clinical practice: If we can analyse pathological endometrial inflammation by measuring endometrial NF-κB p65 (Rel A) expression, treatment could be directed towards eliminating the source of pathological endometrial inflammation.
本研究的目的是调查正常体重和超重的多囊卵巢综合征（PCOS）女性子宫内膜NFκB p65的表达水平是否存在差异，并将其与体重指数（BMI）匹配的无PCOS的对照受试者进行比较。研究组包括20名正常体重（BMI：18.5 - 24.9kg/m²）和15名超重的PCOS不孕女性（BMI：25 - 29.9kg/m²）。招募无PCOS的健康可育女性作为对照组。正常体重PCOS组和对照组的患者在年龄和BMI上相匹配。在黄体中期获取子宫内膜样本进行免疫组织化学染色。采用H评分法评估NF-κB p65（Rel A）的表达。正常体重和超重的PCOS女性的子宫内膜NF-κB p65表达均显著高于无PCOS的女性。两组PCOS女性子宫内膜NF-κB p65表达的H评分相似。在PCOS女性中，NF-κB p65与血清胰岛素、稳态模型评估胰岛素抵抗（HOMA-IR）和总睾酮水平呈正相关。正常体重和超重的PCOS女性子宫内膜中NF-κB p65表达的增加可能通过导致病理性炎症而导致与PCOS相关的生育力低下。影响声明关于该主题已知的信息：尽管PCOS的发病机制尚未阐明，但低度慢性炎症正逐渐被确立为一个重要的致病因素。据报道，PCOS女性中白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）等炎症细胞因子水平升高。病理性子宫内膜炎症的原因可能源于局部子宫内膜疾病或与远处生殖组织的疾病有关。然而，子宫内膜NF-κB作为炎症的基本细胞调节因子在PCOS相关着床缺陷病理生理学中的可能作用尚未阐明。本研究的结果补充了什么：本研究首次对PCOS相关不孕与病理性子宫内膜炎症之间的关系提供了新颖的见解。我们证明了PCOS与病理性子宫内膜炎症之间存在密切关联。此外，我们清楚地表明，病理性子宫内膜炎症在正常体重和超重的PCOS女性中均会发生。此外，在超重的PCOS女性中，发现子宫内膜NF-κB p65（Rel A）表达与血清胰岛素水平和高雄激素血症呈正相关。这些发现对临床实践有何意义：如果我们能够通过测量子宫内膜NF-κB p65（Rel A）表达来分析病理性子宫内膜炎症，那么治疗可以针对消除病理性子宫内膜炎症的源头。
