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

Moreno-Asso, A, Altıntaş, A, McIlvenna, LC, Patten, RK, Botella, J, McAinch, AJ, Rodgers, RJ, Barrès, R and Stepto, NK 2021, Non-cell autonomous mechanisms control mitochondrial gene dysregulation in polycystic ovary syndrome, Journal of Molecular Endocrinology, vol. 68, no. 1, pp. 63-76, doi: 10.1530/JME-21-0212.

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Title Non-cell autonomous mechanisms control mitochondrial gene dysregulation in polycystic ovary syndrome
Author(s) Moreno-Asso, A
Altıntaş, A
McIlvenna, LC
Patten, RK
Botella, J
McAinch, AJ
Rodgers, RJ
Barrès, R
Stepto, NK
Journal name Journal of Molecular Endocrinology
Volume number 68
Issue number 1
Start page 63
End page 76
Total pages 14
Publisher Bioscientifica
Place of publication Bradley Stok, Eng.
Publication date 2021
ISSN 0952-5041
1479-6813
Keyword(s) mitochondria
myotubes
polycystic ovary syndrome
skeletal muscle
transcriptomics
Summary 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.
Language eng
DOI 10.1530/JME-21-0212
Indigenous content off
Field of Research 0707 Veterinary Sciences
1103 Clinical Sciences
1114 Paediatrics and Reproductive Medicine
HERDC Research category C1 Refereed article in a scholarly journal
Free to Read? Yes
Persistent URL http://hdl.handle.net/10536/DRO/DU:30161739

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
Open Access Collection
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.