Mitochondrial Dysfunction and Oxidative stress activation in Adolescent Girls with Polycystic Ovary Syndrome and Excessive Body Weight

Elena Khashchenko (RU), Mikhail Vysokikh (RU), Marya Volodina (RU), Elena Uvarova (RU), Iuliia Sykhanova (RU), Sonya Pyataeva (RU), Gennadiy Sukhikh (RU)

[Khashchenko] National Medical Research Center for Obstetrics Gynecology and Perinatology, [Vysokikh] National Medical Research Center for Obstetrics Gynecology and Perinatology, [Volodina] National Medical Research Center for Obstetrics Gynecology and Perinatology, [Uvarova] National Medical Research Center for Obstetrics Gynecology and Perinatology, [Sykhanova] National Medical Research Center for Obstetrics Gynecology and Perinatology, [Pyataeva] National Medical Research Center for Obstetrics Gynecology and Perinatology, [Sukhikh] National Medical Research Center for Obstetrics Gynecology and Perinatology

Context: Oxidative stress (OS) due to mitochondrial dysfunction plays an essential role in the pathogenesis of PCOS and related complications. Objective: To evaluate the impact of mitochondrial dysfunction in PCOS pathogenesis during adolescence with regard to body mass index Methods: Clinical and laboratory examination; CRP, malondialdehyde (MDA), reduced (GSH) and the oxidized glutathione (GSSG) (spectrophotometry); catalase (CAT), glutathione peroxidase (GP) and reductase (GR) activity in plasma (GPx) (kinetic analysis), % of highly polarized mononuclear cells (MNC). Patients: The study included adolescents from 15 to 17 years old: 90 girls with PCOS according to the Rotterdam criteria (60 lean with BMI<15 kg/m²; 30 - with excessive BMI≥25 kg/m²); 30 healthy girls with regular menses in control group. Results: The difference was observed between the PCOS Lean and Obese versus Control group for levels of hemaglobin, (g/l) (in lean 131,9±8,6 vs. obese 131,3±13,2 vs. 126,7±10,4 controls, p <,05 Mann-Whitney U-test), hematocrit (0,407±0,021:3 vs. 0,408±0,032:3 vs. 0,39±0,01; p1:2<,05, p2:3<,02), bilirubin conjugated (umol/ml) (4,5±2,31:3 vs. 3,9±2,3 vs. 3,3±1,11:3, p 1:3<,02). In lean and obese girls with PCOS compared between themselves and the control group oxidative stress indicators and mitochondria dysfunction parameters appeared to be diametrically different: MDA, μM (4,4±1,01:3 vs. 5,3±0,91:2 vs. 5,0±0,7, 1:3, 1:2p≤,005), GSH, μM (1258,7±551,61:3 vs. 961,5±181,21:2 vs. 889,5±168,1, 1:3p≤,0001, 1:2p≤,005) GR, A,Umin-1 (0,021±0,01:3 vs. 0,027±0,01:2 vs. 0,029±0,0, 1:3, 1:2p≤,0001), GPx, A,Umin-1 (0,312±0,11:3 vs. 0,291±0,1 vs. 0,339±0,1, 1:3p≤,005), CAT (34,7±28,51:3 vs. 39,1±18,2 vs. 43,8±31,8, 1:3p≤,005), %of highly polarized MNC (57,3±12,91:3 vs. 54,2±11,8 vs. 51,2±8,7, 1:3p≤,05). Significant positive correlation was observed CRP and MDA level in whole group of PCOS (0,32, p≤,05). Conclusions: The study supports the different mechanisms of PCOS pathogenesis in lean and obese adolescents by alteration of mitochondrial function in the background of OS. In lean girls with PCOS adaptation is evidenced by the reduction of OS simultaneously with the increase of heme metabolism in highly coupled mitochondria. In obese patients with PCOS due to cholesterol excess and violations of glucose utilization the amount of uncoupled mitochondria increases, transmembrane potential decreases, reduction of the intensity of heme metabolism is observed.