Our ‘Dataset of the Week’ series features publicly available omics datasets of scientific value, intending to promote data sharing and reuse.

This week’s dataset comprises of microarray data using the Affymetrix platform from the publication titled ‘Pioglitazone Enhances Mitochondrial Biogenesis and Ribosomal Protein Biosynthesis in Skeletal Muscle in Polycystic Ovary Syndrome’1.

Polycystic Ovarian Syndrome (PCOS) is a metabolic disorder that affects around 10% of women worldwide2. The most commonly described symptoms are polycystic ovaries, menstrual irregularities and infertility. Additionally, numerous lines of evidence have shown that women affected by this disorder have high levels of insulin resistance, putting them at risk of developing Type 2 diabetes3,4. The molecular mechanisms by which insulin resistance contributes to PCOS pathogenesis are poorly understood. This publication used a microarray-based approach to examine how insulin sensitivity improves in patients who are treated with thiazolidinediones (TZDs), a class of drugs with anti-diabetic effects.

Key Findings of the Publication:

• Treatment with pioglitazone, a TZD, improved insulin sensitivity in PCOS patients by increasing glucose transport by 36% in skeletal muscles.
• Global transcriptomic profiling and pathway analysis using GenMAPP and GSEA revealed that the top significantly upregulated pathways were related to oxidative phosphorylation (OXPHOS), ribosomal proteins, mRNA processing reactome and electron transport chain.
• Validation with quantitative real-time PCR showed that the observed upregulation of OXPHOS genes was mediated by increased PGC-1a expression.
• Taken together, these results point to a potential mechanism involving mitochondrial oxidative phosphorylation, by which pioglitazone restores insulin sensitivity in PCOS patients.

Significance of the Dataset:

This dataset contains microarray data from skeletal muscle tissues of pioglitazone-treated patients affected with PCOS and healthy controls. Exploring the transcriptomes of these patients could aid the effort to unravel the role of insulin resistance in the molecular pathogenesis of PCOS.

Experimental Design:

Skeletal muscle tissue biopsies from Caucasian PCOS patients and healthy volunteers whose BMIs fell under the obese range were obtained before and after treatment with pioglitazone (30mg/day for 16 weeks, n=10 for PCOS patients, n=13 for healthy volunteers). Total RNA was isolated and microarray analysis was carried out using the Affymetrix platform.

Useful links:

• The dataset (GEO7775): https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE7775
• The publication: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0002466#:~:text=These%20data%20indicate%20that%20pioglitazone,biosynthesis%20in%20muscle%20in%20PCOS.

References:

1. Skov, V., Glintborg, D., Knudsen, S., Tan, Q. & Jensen, T. Pioglitazone Enhances Mitochondrial Biogenesis and Ribosomal Protein Biosynthesis in Skeletal Muscle in Polycystic Ovary Syndrome. PLoS One 3, 2466 (2008).
2. Wolf, W. M., Wattick, R. A., Kinkade, O. N. & Olfert, M. D. Geographical prevalence of polycystic ovary syndrome as determined by region and race/ethnicity. International Journal of Environmental Research and Public Health vol. 15 (2018).
3. Macut, D., Bjekić-Macut, J., Rahelić, D. & Doknić, M. Insulin and the polycystic ovary syndrome. Diabetes Research and Clinical Practice vol. 130 163–170 (2017).
4. Dunaif, A. Insulin Resistance and the Polycystic Ovary Syndrome: Mechanism and Implications for Pathogenesis*. Endocr. Rev. 18, 774–800 (1997).