Transcriptome Analysis of Mesenchymal Progenitor Cells Revealed Molecular Insights into Metabolic Dysfunction and Inflammation in Polycystic Ovary Syndrome

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Jul 27

PMID 39063189

Authors

Mei-Chi Huang

Pei-Lung Chen

Chia-Lang Hsu

Affiliations

Soon will be listed here.

Abstract

Polycystic ovary syndrome (PCOS) is a female endocrine disorder with metabolic issues. Hyperandrogenism combined with hyperinsulinemia exacerbates the reproductive, metabolic, and inflammatory problems in PCOS patients. The etiology of PCOS is unclear. Patient-specific induced pluripotent stem cells (iPSCs) offer a promising model for studying disease mechanisms and conducting drug screening. Here, we aim to use mesenchymal progenitor cells (MPCs) derived from PCOS iPSCs to explore the mechanism of PCOS. We compared the transcriptome profiles of PCOS and healthy control (HC) iPSC-derived MPCs (iPSCMs). Moreover, we assess the impact of androgens on iPSCMs. In the comparison between PCOS and HC, the expression levels of 1026 genes were significantly different. A gene set enrichment analysis (GSEA) revealed that adipogenesis- and metabolism-related genes were downregulated, whereas inflammation-related genes were upregulated in the PCOS iPSCMs. Dysregulation of the TGF-β1 and Wnt signaling pathways was observed in the PCOS iPSCMs. Furthermore, there was impaired adipogenesis and decreased lipolysis in the PCOS iPSCMs-derived adipocytes. With testosterone treatment, genes related to metabolism were upregulated in the HC iPSCMs but downregulated in the PCOS iPSCMs. The impact of testosterone varied among HCs and PCOS iPSCMs, possibly because of a genetic predisposition toward PCOS. This study found specific signaling pathways that could serve as therapeutic targets for PCOS.

Citing Articles

Gut microbiota and gut-derived metabolites are altered and associated with dietary intake in women with polycystic ovary syndrome.

da Silva T, Marchesan L, Rampelotto P, Longo L, de Oliveira T, Landberg R J Ovarian Res. 2024; 17(1):232.

PMID: 39578890 PMC: 11583432. DOI: 10.1186/s13048-024-01550-w.

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