Activation of systemic inflammation and oxidative stress in adolescent girls with polycystic ovary syndrome in combination with metabolic disorders and excessive body weight
Open accessAbstract
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.
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PCOS involves two-way relationships between androgen excess, adipose dysfunction, IR, inflammation, and oxidative stress.
“However, this process has several vicious circles, with two-way relationships between androgen excess, adipose dysfunction, IR, and other actors, such as inflammation [24], and oxidative stress [25,26]”
From PCOS and nutritional approaches: Differences between lean and obese phenotype (2021) · cites this paper as [26]
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- Authors
- Khashchenko, E., Vysokikh, M., Uvarova, E., Krechetova, L., Vtorushina, V., Ivanets, T., Volodina, M., Tarasova, N., Sukhanova, I., & Sukhikh, G.
- Affiliations
- 2nd Gynecological Department for Children and Adolescents, FSBI “National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I. Kulakov” Ministry of Healthcare of the Russian Federation, 117997 Moscow, Russia
- National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I.Kulakov of the Ministry of Healthcare of the Russian Federation (RU)
- Laboratory of Clinical Immunology, FSBI “National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I. Kulakov” Ministry of Healthcare of the Russian Federation, 117997 Moscow, Russia
- National Research University Higher School of Economics (RU)
- Sechenov University (RU)
- Corresponding author
- Vysokikh, Mikhail
- ORCID
- Venue
- Journal of Clinical Medicine
- Publisher
- MDPI AG
- Published
- 2020-05-09
- Volume
- 9
- Issue
- 5
- Pages
- 1399
- ISSN
- 2077-0383 (ISSN-L)
- PMC
- PMC7291245
- OpenAlex
- W3021737588
- Cited by
- 64
- References
- 25
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 12 · 2023: 11 · 2022: 9 · 2021: 17 · 2020: 5
- FWCI
- 9.25
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Journal of Clinical Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Keywords
- polycystic ovary syndrome, adolescent girls, systemic inflammation, oxidative stress, mitochondrial dysfunction, metabolic disorders, insulin resistance, overweight, obesity, C-reactive protein, leptin, malondialdehyde, macrophage migration inhibitory factor, cytokines, sFas, IL-18, interleukin-6, IL-10, TNF-α
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