Despite polycystic ovary syndrome (PCOS) being highly prevalent, the aetiology of the disease is unclear. Now, new research demonstrates that transcriptional and epigenetic changes in skeletal muscle could contribute to the metabolic abnormalities (such as an increased risk of insulin resistance and type 2 diabetes mellitus) seen in women with PCOS.

Previous work has shown that transcriptional and epigenetic changes are present in the adipose tissue of women with PCOS. “As skeletal muscle accounts for the vast majority of glucose uptake, we decided to investigate differential DNA methylation and gene expression in skeletal muscle in women with PCOS and control individuals matched for weight, BMI and age,” explains corresponding author Elisabet Stener-Victorin.

The researchers took muscle biopsy samples from 17 women with PCOS and 14 control individuals, which were then analysed using array-based DNA methylation and mRNA expression profiling. These analyses revealed that 85 transcripts were differentially expressed between the cases and controls; 66% were upregulated and 34% were downregulated in the women with PCOS. Several of the identified differentially expressed genes are known to be involved in muscle function and metabolism, including COL1A1 and MAP2K6.

In addition, a gene-set enrichment analysis showed that women with PCOS had notable genetic alterations in 16 different pathways, many of which are known to be involved in the immune response or have been implicated in immune-related diseases. “Furthermore, we were able to identify, for the first time, specific changes in skeletal muscle DNA methylation that might affect gene expression,” explains Stener-Victorin. “Thus, we demonstrate that women with PCOS have epigenetic and transcriptional changes in skeletal muscle that, in part, explain the metabolic abnormalities seen in these women.”

Stener-Victorin and her colleagues are now hoping to investigate whether specific therapies can be used to remodel the genetic alterations in PCOS, with the aim of improving whole body glucose homeostasis.