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

Gynecol Endocrinol. 2019 Oct;35(10):842-846. doi: 10.1080/09513590.2019.1599349. Epub 2019 Apr 9.

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.

Keywords: CFTR; FOXO1; HMGB1; IL-6; PCOS; inflammation; insulin.

MeSH terms

  • Adult
  • Cystic Fibrosis Transmembrane Conductance Regulator / blood
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
  • Female
  • Fertilization in Vitro
  • Forkhead Box Protein O1 / blood
  • Forkhead Box Protein O1 / genetics
  • Forkhead Box Protein O1 / metabolism*
  • Gene Expression Regulation
  • HMGB1 Protein / blood
  • HMGB1 Protein / genetics
  • HMGB1 Protein / metabolism*
  • Humans
  • Insulin / metabolism
  • Interleukin-6 / metabolism
  • Ovary / metabolism*
  • Polycystic Ovary Syndrome / blood
  • Polycystic Ovary Syndrome / genetics
  • Polycystic Ovary Syndrome / metabolism*
  • Young Adult

Substances

  • CFTR protein, human
  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • HMGB1 Protein
  • Insulin
  • Interleukin-6
  • Cystic Fibrosis Transmembrane Conductance Regulator