Indicators of mitochondrial functioning in adolescent girls with polycystic ovary syndrome with regard to the presence of metabolic disorders and overweight

There is a growing body of evidence supporting the significant role of systemic inflammation and oxidative stress in the genesis of polycystic ovary syndrome (PCOS) in adult patients. The indicators of mitochondrial functioning early in the development of PCOS in adolescence remain little studied. Objective. To study the characteristics of mitochondrial function and systemic inflammation in adolescent girls with different metabolic PCOS phenotypes compared with healthy girls. Subjects and methods. The investigation enrolled 95 girls aged 15 to 17 years inclusive with PCOS according to the Rotterdam criteria. A control group consisted of 30 healthy age-matched regularly cycling girls. All the participants underwent a complete clinical and instrumental examination and estimation of the levels of C-reactive protein, malondialdehyde (MDA), the mitochondrial membrane potential of peripheral blood mononuclear cells (MNC) and MNC fractions with highly polarized mitochondria. The level of glutathione, the ratio of its oxidized (GSSH) to reduced (GSH) forms (GSSR/GSH), and the enzymatic activity of catalase, glutathione reductase and glutathione peroxidase were determined. Results. As compared with the healthy girls, the normal weight patients with PCOS in the absence of metabolic abnormalities (PCOS-MANW) had a lower concentration of MDA, decreased activity of the antioxidant enzyme glutathione reductase, a higher level of the reduced form of the antioxidant glutathione and its ratio to the oxidized form, and a higher percentage of MNCs with highly polarized mitochondria (p <0.05 for all indicators). The patients with PCOS-MANW showed lower C-reactive protein (CRP) and MDA levels than those with PCOS-MA_OW) (p < 0.05). The girls with PCOS-MA_OW) had higher levels of CRP and enhanced glutathione reductase and MDA activities than those with PCOS-MANW (p < 0.05). Comparison of the girls PCOS+MAOW) and those with PCOS+MANWrevealed significant increases in the levels of CRP and MDA and the activity of glutathione reductase (p < 0.05). The girls with PCOS-MAOWhad a higher MDA level than those with PCOS+MANW(p < 0.05). As compared with the healthy girls, the PCOS+MANWgroup had a lower level of MDA, an elevated concentration of reduced glutathione, and lower activity of glutathione reductase (p < 0.05). The found characteristics are confirmed by a correlation analysis and by the results of two-factor analysis of variance. Conclusion. An adaptive mechanism for reducing the manifestations of oxidative stress and systemic inflammation with the high coupling of mitochondrial respiration and the level of antioxidant protection is realized in the normal weight adolescents with PCOS. The manifestations of oxidative stress, which are mediated by mitochondrial uncoupling due to impaired cholesterol and glucose metabolism, are pronounced, which is enhanced by the addition of carbohydrate metabolic disturbances in the overweight adolescents with PCOS. Mitochondrial dysfunction is associated with the activation of systemic inflammatory response in the overweight adolescents with PCOS in the presence of insulin resistance.

polycystic ovary syndrome, insulin resistance, systemic inflammation, mitochondrial dysfunction, glutathione, glutathione reductase, glutathione perioxidase