Nuclear factor-κB expression in the endometrium of normal and overweight women with polycystic ovary syndrome

Abstract

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/m2) and 15 overweight PCOS women (BMI: 25–29.9 kg/m2) 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 statementWhat 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.