Reduced serum and skeletal muscle MOTS c levels in women with polycystic ovary syndrome are associated with mitochondrial dysfunction

TL;DR

Women with polycystic ovary syndrome have lower levels of MOTS-c in their blood and muscles, which may be linked to mitochondrial dysfunction and metabolic issues.

Contribution

This study is the first to show reduced MOTS-c levels in both serum and skeletal muscle in PCOS patients.

Findings

PCOS patients had significantly lower serum MOTS-c levels compared to healthy controls.

Skeletal muscle MOTS-c expression was also reduced in PCOS patients.

Lower MOTS-c levels were associated with higher testosterone and cholesterol in PCOS patients.

Abstract

Polycystic ovary syndrome (PCOS) is characterized by insulin resistance and metabolic dysfunction. Mitochondrial-derived peptides (MDPs), including MOTS-c, regulate glucose homeostasis and skeletal muscle metabolism. Whether MOTS-c expression is altered in PCOS across different physiological compartments remains unknown. The aim was to assess circulating and skeletal muscle MOTS-c levels in women with PCOS and to examine their associations with metabolic and hormonal parameters. Forty women with PCOS and 40 age- and BMI-matched healthy controls underwent clinical, biochemical, and hormonal phenotyping. Serum MOTS-c concentrations were quantified by ELISA. In a representative subgroup, skeletal muscle MOTS-c expression was assessed in vastus lateralis biopsy specimens using Western blotting. Women with PCOS exhibited lower circulating MOTS-c concentrations compared with controls (220.2 ± 147.6 pg/mL vs. 498.3 ± 224.4 pg/mL, p < 0.001). Skeletal muscle MOTS-c expression was also reduced in the PCOS group (74.2 ± 15.2 vs. 100.0 ± 8.5 arbitrary units; p = 0.005). Serum MOTS-c levels were inversely associated with total testosterone (r = − 0.224, p = 0.046) and total cholesterol (r = − 0.228, p = 0.044). Women with PCOS display reduced MOTS-c expression in both the circulation and skeletal muscle, suggesting reduced availability of this mitochondrial-derived peptide. Associations with hyperandrogenism and lipid profiles suggest a potential link between altered mitochondrial peptide biology and the endocrine–metabolic phenotype of PCOS. These findings suggest that MOTS-c may represent a potential marker of tissue-specific mitochondrial involvement in PCOS and warrant further investigation.

The online version contains supplementary material available at 10.1038/s41598-026-39687-x.

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