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Non-cell autonomous mechanisms control mitochondrial gene dysregulation in polycystic ovary syndrome

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Version 3 2024-06-19, 08:13
Version 2 2024-06-13, 15:07
Version 1 2022-01-20, 08:09
journal contribution
posted on 2024-06-19, 08:13 authored by A Moreno-Asso, A Altıntaş, LC McIlvenna, RK Patten, J Botella, AJ McAinch, RJ Rodgers, R Barrès, NK Stepto
Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with insulin resistance and impaired energy metabolism in skeletal muscle, the aetiology of which is currently unclear. Here, we mapped the gene expression profile of skeletal muscle from women with PCOS and determined if cultured primary myotubes retain the gene expression signature of PCOS in vivo. Transcriptomic analysis of vastus lateralis biopsies collected from PCOS women showed lower expression of genes associated with mitochondrial function, while the expression of genes associated with the extracellular matrix was higher compared to controls. Altered skeletal muscle mRNA expression of mitochondrial-associated genes in PCOS was associated with lower protein expression of mitochondrial complex II–V, but not complex I, with no difference in mitochondrial DNA content. Transcriptomic analysis of primary myotube cultures established from biopsies did not display any differentially expressed genes between controls and PCOS. Comparison of gene expression profiles in skeletal muscle biopsies and primary myotube cultures showed lower expression of mitochondrial and energy metabolism-related genes in vitro, irrespective of the group. Together, our results show that the altered mitochondrial-associated gene expression in skeletal muscle in PCOS is not preserved in cultured myotubes, indicating that the in vivo extracellular milieu, rather than genetic or epigenetic factors, may drive this alteration. Dysregulation of mitochondrial-associated genes in skeletal muscle by extracellular factors may contribute to the impaired energy metabolism associated with PCOS.

History

Journal

Journal of Molecular Endocrinology

Volume

68

Pagination

63-76

Location

England

Open access

  • Yes

ISSN

0952-5041

eISSN

1479-6813

Language

English

Publication classification

C1 Refereed article in a scholarly journal

Issue

1

Publisher

BIOSCIENTIFICA LTD