CFTR and FOXO1 gene expression are reduced and high mobility group box 1 (HMGB1) is increased in the ovaries and serum of women with polycystic ovarian syndrome

Abstract

We previously described increased HMGB1 and reduced FOXO1 dependent on CFTR loss of function in cystic fibrosis (CF) and we showed in vitro that HMGB1 was lowered by insulin. Reduced CFTR gene expression has been described in granulosa cells (GC) from PCOS-induced rats. We aimed at studying CFTR and FOXO1 gene expression in GC, HMGB1 concentrations in serum and follicular fluids (FF), and insulin and IL-6 in FF in PCOS women. Thirty PCOS and 36 non-PCOS women (CTRL) undergoing in vitro fertilization were enrolled. CFTR and FOXO1 gene expression were downregulated in PCOS (p ≤ .05). HMGB1 was higher in PCOS both in FF (p ≤ .05) and in serum (p < .005) whereas insulin was lower, and IL-6 was unchanged with respect to controls. 17-β estradiol was higher in PCOS than in CTRL (p ≤ .005). HMGB1 correlated negatively with insulin in FF (p ≤ .005). The increase in HMGB1 both in FF and in serum, likely reflects both low grade inflammation and insulin sensitivity. IL-6 was unchanged possibly reflecting functions other than inflammation.

摘要

我们先前描述了依赖于CFTR的HMGB1增加和FOXO1降低在囊性纤维化（CF）中功能丧失, 并且我们体外表明HMGB1被胰岛素降低。来自PCOS诱导大鼠的颗粒细胞（GC）中描述了降低的CFTR基因表达。我们的目的是研究GC中的CFTR和FOXO1基因表达, PCOS女性血清和卵泡液（FF）中的HMGB1浓度以及FF中的胰岛素和IL-6。招募了30名接受体外受精的PCOS和36名非PCOS女性（CTRL）。PCOS中CFTR和FOXO1基因表达下调（p≤0.05）。相比于对照组, HMGB1在FF（p≤0.05）和血清（p <0.005）中较高, 而胰岛素较低, IL-6没有变化。PCOS中的17-β雌二醇高于CTRL（p≤0.005）。在FF中HMGB1与胰岛素呈负相关（p≤0.005）。在FF和血清中HMGB1的增加可能反映了低度炎症和胰岛素敏感性。IL-6没有变化, 可能反映炎症以外的功能。

The Chinese abstracts are translated by Prof. Dr. Xiangyan Ruan and her team: Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China.

Keywords:

• HMGB1
• PCOS
• CFTR
• FOXO1
• insulin
• inflammation
• IL-6

Acknowledgments

We are indebted to Laborest Italia S.r.l. for their unconditioned support to this research which allowed us to buy some reagents and contribute to a salary. We thank Prof. S. Palomba for helpful revision of this manuscript, and P. Mancuso for help with the statistical analysis. This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Disclosure statement

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of this study.