Mitochondrial DNA oxidation and content in different metabolic phenotypes of women with polycystic ovary syndrome

Abstract

Introduction: Polycystic Ovary Syndrome (PCOS) affects 5-20% of reproductive-aged women. Insulin resistance (IR) is common in PCOS with consequent elevated risks of metabolic disorders and cardiovascular mortality. PCOS and obesity are complex conditions associated with Metabolic Syndrome (MS), contributing to cardiovascular disease and type 2 diabetes mellitus (T2D). Obesity and PCOS exacerbate each other, with central obesity driving metabolic changes. Mitochondrial dysfunction, characterized by oxidative stress and reduced antioxidant capacity, plays a key role in PCOS pathology.

Methods: In our study, we investigated 81 women with PCOS, and 57 control women aged 16 to 46 years old. Relative mitochondrial DNA (mtDNA) content and its oxidation level (8-oxoguanine, 8-OxoG) were determined in peripheral blood leukocytes by the SYBR Green method real-time PCR.

Results: Our findings showed that patients with PCOS had decreased mtDNA content and increased oxidation damage. Stratifying these patients by metabolic profile, revealed a progressive decline in mtDNA content from the normal-weight control group to the MHO-PCOS and MUO-PCOS groups, suggesting that lower mtDNA content is linked to obesity and worse metabolic profile. However, mtDNA oxidation levels did not differ significantly among these groups. Additionally, the decline in mtDNA content and the increase in oxidation levels between controls and patients with PCOS lost significance when these relationships were adjusted for the HOMA index.

Discussion: This finding suggests that IR could be the main factor contributing to mitochondrial dysfunction in PCOS. Maintaining optimal mtDNA copies are crucial for mitochondrial and cell function, suggesting potential therapeutic targets for PCOS-associated metabolic disturbances.

Keywords: metabolic syndrome; mitochondrial DNA; obesity; oxidative damage; polycystic ovary syndrome.

Figure 1

Comparative study of mtDNA content between groups (A) Comparison of mtDNA content between control and PCOS group. (B) Comparison of mtDNA content between control, MHO-PCOS and MUO-PCOS groups. MHO-PCOS: Metabolically healthy with polycystic ovary syndrome women, MUO-PCOS: metabolically unhealthy with polycystic ovary syndrome women; Comparison of means using Student’s Test, ANOVA and Tukey post hoc. *It is considered significant with an age-corrected p-value<0.05. NS, Not Significant.

Figure 2

Comparative study of mtDNA oxidation levels between groups (A) Comparison of mtDNA oxidation levels between control and PCOS group. (B) Comparison of mtDNA oxidation levels between control, MHO-PCOS and MUO-PCOS groups. MHO-PCOS: Metabolically-healthy with polycystic ovary syndrome women, MUO-PCOS: metabolically unhealthy with polycystic ovary syndrome women; Comparison of means using Student’s Test, ANOVA and Tukey post hoc. *It is considered significant with an age-corrected p-value<0.05. NS, Not Significant.

Figure 3

Relationship between mtDNA content and its oxidation level with BMI. (A) With mtDNA content. (B) With 8-OxoG. BMI: body mass index, *It is considered significant with an age-corrected p-value<0.05.

Figure 4

Relationship between mtDNA content and its oxidation level with WC. (A) With mtDNA content. (B) With 8-OxoG. WC: waist circumference, *It is considered significant with an age-corrected p-value<0.05.

Figure 5

Relationship between mtDNA content and its oxidation level with insulin resistance. (A) With mtDNA content. (B) With 8-OxoG. HOMA index: Homeostatic Model Assessment for Insulin Resistance, *It is considered significant with an age-corrected p-value<0.05. NS, Not Significant.