Abstract
Relevance: Mitochondrial dysfunction and systemic inflammation are believed to play pivotal role in the pathogenesis of polycystic ovary syndrome (PCOS) and related complications of metabolic disorders in adult patients. Though such researches are limited or almost absent in adolescents. The aim of the study is to evaluate the impact of mitochondrial dysfunction and systemic inflammation on PCOS pathogenesis during adolescence with regard to body mass index and insulin resistance. Design: a case-control study. Methods: The study included 95 adolescent girls (15 to 17 years old inclusive) diagnosed with PCOS based on the Rotterdam criteria. The control group consisted of 30 healthy girls of the same age with a regular menstrual cycle. All participants were subjected to a full clinical and instrumental examination, as well as an assessment of the levels of leptin, C-reactive protein (CRP), and malondialdehyde (MDA) as oxidative stress marker. Serum levels of IL-6, IL-10, IL-18, TNF-α, and plasma concentrations of macrophage migration inhibitory factor (MIF), sFas, and sFasL were determined. Patients with PCOS were divided into groups according to the presence of metabolic disorders (MD) (impaired glucose tolerance and/or over insulin resistance) and normal weight or excessive weight (NW or OW). Results: Patients with PCOS of NW in the absence of metabolic disorders (MD−/NW) had a lower concentration of MDA and a higher level of IL-10 compared to healthy girls (p < 0.05). The group (MD−/NW) was characterized with lower levels of CRP, leptin, MDA, and higher levels of sFasL, when compared to OW patients with PCOS in the absence of metabolic disorders (MD−/OW) (p < 0.05). Overweight adolescent girls with PCOS and metabolic disorders (MD+/OW) showed higher CRP, leptin, and a two-fold increase in IL-6 and IL-18 concentrations compared to the control group of healthy girls (p < 0.05 for all parameters). The group (MD+/OW) was also characterized with higher levels of CRP, leptin, MDA, IL-18, MIF (p < 0.05), when compared to overweight patients with PCOS in the absence of metabolic disorders (MD−/NW). In comparison with the MD−/OW group, the obese insulin resistant girls with PCOS (MD+/OW) had a highera level of IL-18 (p < 0.05). Moreover, the MD+/OW girls demonstrated a significant increase in CRP, MDA and IL-18 levels when compared to the MD+/NW group (p < 0.05). OW girls with PCOS without MD (MD−/OW) had lower concentrations of sFasL compared to healthy girls (p < 0.05), and higher levels of MDA compared to MD+/NW (p < 0.05). Adolescent girls of NW with PCOS and with MD (MD+/NW) had lower levels of MDA compared to the control group of healthy girls (p < 0.05). These data are confirmed by a correlation analysis and two-factor ANOVA test. Conclusions: Lean girls with PCOS demonstrate the protective mechanism of decrease in oxidative stress mediated by the activation of antioxidant defense, reduction of lipid peroxidation and systemic inflammation. Excessive weight and metabolic disorders in adolescents with PCOS are the most significant factors in reducing the capacity of antioxidant systems, activation of oxidative stress, mitochondrial dysfunction, and systemic inflammation.
Highlights
Polycystic ovary syndrome (PCOS) is a chronic syndrome, that most frequently manifests in adolescence and observed in 3% to 30% cases [1]
polycystic ovary syndrome (PCOS) is usually associated with multiple metabolic disorders (MD) that change with age, from insulin resistance (IR) in adolescents, to dyslipidemia, obesity, arterial hypertension, fatty hepatosis, type 2 diabetes, and an increased risk of myocardial infarction that usually occur in adulthood [2,3,4]
We demonstrate that the group of OW girls with PCOS had higher levels of C-reactive protein (CRP) compared to other groups of girls with normal body mass index (BMI) values with (p = 0.0127) or without (p = 0.0226) MD (Table 2)
Summary
Polycystic ovary syndrome (PCOS) is a chronic syndrome, that most frequently manifests in adolescence and observed in 3% to 30% cases [1]. There is a growing number of publications nowadays that demonstrate the relationship between chronic systemic inflammation and mitochondrial dysfunction as well as their significance in the etiology of PCOS and its long-term consequences [2,6,7]. It was found that the development of PCOS among patients of reproductive age is accompanied by systemic increase of oxidative stress that occurs because of mitochondrial dysfunction and reduced antioxidant protection [7,8,9]. It has been shown that, compared to healthy women of reproductive age, PCOS patients have increased blood levels of lymphocyte and monocyte counts, as well as elevated levels of C-reactive protein (CRP), proinflammatory cytokines (tumor necrosis factor-α (TNF- α), interleukins (IL-1, IL-6, IL-18)) and high levels of lipid peroxidation, protein carbonylation products and advanced oxidation protein products [10,11]
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