High Mobility Group Box 1 (HMGB1) is Increased in Adolescents with Polycystic Ovarian Syndrome (PCOS) and Decreases After Treatment with Myo-Inositol in Combination with A-Lipoic Acid (MYO plus ALA)

HMGB1 is a small-protein which reflects both inflammation and insulin-sensitivity. Inflammation and insulin-resistance are features of PCOS. IL-6 is important for ovarian function and can contribute to insulin-resistance. IGFBP-2 behaves like an acute-phase protein and is increased in chronic inflammation. It is also involved in the glucose-metabolism regulation and IGFBP-2 overexpression plays a protective role against insulin-resistance. Insulin functions as a co-gonadotropin modulating ovarian steroidogenesis and hyperinsulinism contributes to hyperandrogenism, a cause of arrest of follicular maturation present in PCOS. We aimed at assessing HMGB1, IGFBP-2, insulin and IL-6 concentrations and their relationships in FF from PCOS vs non-PCOS. We enrolled, 30 women (CA:34.43±0.84 years; BMI: 25.92±0.99 kg/m2; hirsute N.12; amenorrhoic N.2; oligomenorrhoic N.13; regular cycling N.15) with PCOS according to the Rotterdam Criteria, and 36 women (CA:35.72±0.55 years; BMI: 24.08±0.79 kg/m2), fertile oocyte donors, with tubarian or unknown infertility causes, with normal endocrine exams, regular menstrual-cycles, no hyperandrogenism as controls (CTRL) all undergoing the same ovarian stimulation protocol for IVF. HMGB1 both in FF and in serum, IGFBP-2, IL-6 and insulin in FF were assayed using specific ELISAkits. Serum estradiol (E2) at oocyte retrieval was quantified. The N. of dominant follicles (>17 mm) at ultrasound was also considered. Statistical analyses was performed using SPSSv23.0. HMGB1 in FF was higher in PCOS than in CTRL (46.09±4.25 vs 26.53±1.87 ng/ml; P=0.002). IL-6 was similar in PCOS and in CTRL (11.52±1.92 vs 11.76±1.26 pg/ml; n.s.). IGFBP-2 was higher in PCOS than in CTRL (719.15±37.99 vs 630.16±21.13 ng/ml; P=0.030). Insulin was lower in PCOS than in CTRL (1.50±0.20 vs 3.72±0.46 mU/l; P<0.001). Serum HMGB1 was confirmed higher in PCOS than in CTRL (17.47±1.84 vs 11.13±1.23 ng/ml; P=0.017). HMGB1 in FF correlated with IGFBP-2 (r=0.345; P=0.005) and insulin (r=−0.452; P=0.004). Insulin correlated with IGFBP-2 (r=−0.361; P=0.033), and the N.of dominant follicles (r=−0.433; P=0.008). HMGB1 both in FF and in serum and IGBFP-2 in FF were increased in PCOS, whereas insulin was decreased and IL-6 unchanged. IL-6 probably reflects other functions than inflammation. HMGB1 and IGFBP-2 reflect both inflammation and insulin concentrations. The low insulin and high IGFBP-2 in FF from PCOS confirms that insulin-sensitivity is not well understood yet in the ovary.