<i>CFTR</i> and <i>FOXO1</i> 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 <i>FOXO1</i> dependent on <i>CFTR</i> loss of function in cystic fibrosis (CF) and we showed <i>in vitro</i> that HMGB1 was lowered by insulin. Reduced <i>CFTR</i> gene expression has been described in granulosa cells (GC) from PCOS-induced rats. We aimed at studying <i>CFTR</i> and <i>FOXO1</i> 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 <i>in vitro</i> fertilization were enrolled. <i>CFTR</i> and <i>FOXO1</i> gene expression were downregulated in PCOS (<i>p</i> ≤ .05). HMGB1 was higher in PCOS both in FF (<i>p</i> ≤ .05) and in serum (<i>p</i> < .005) whereas insulin was lower, and IL-6 was unchanged with respect to controls. 17-β estradiol was higher in PCOS than in CTRL (<i>p</i> ≤ .005). HMGB1 correlated negatively with insulin in FF (<i>p</i> ≤ .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.