Transcriptomic profile of GLCs of PCOS women highlights metabolic dysregulation as a plausible contributor to PCOS pathophysiology

Polycystic ovary syndrome (PCOS) is a complex heterogeneous disorder with reproductive and metabolic con-sequences whose aetiology is still elusive. To understand the cellular mechanisms that potentially govern follicular defect in women with PCOS, we performed transcriptomic profiles of granulosa-lutein cells (GLCs) by RNA-Seq analysis. We found differential expression of 876 genes in GLCs between PCOS and controls that belonged to various processes such as cell cycle, extracellular matrix organization, angiogenesis, oxidative stress, metabolism, etc. that support folliculogenesis, oocyte development, and maturation. The cross-talk between oocyte and GLCs is a fundamental cornerstone in determining oocyte quality and highly interlinked pathways of metabolism and redox homeostasis may influence this. We found several genes involved in the metabolism of carbohydrates, nucleotides, cholesterol, and lipids were dysregulated, which may impair the supply of metab-olites to the growing oocyte, affecting oocyte development and competence. Additionally, high metabolic ac-tivity during folliculogenesis may augment oxidative damage to cells and macromolecules if not counter-balanced. We observed dysregulation of redox homeostasis and AGE-RAGE signalling in the follicular environ-ment. Among the validated genes, prokineticin-1 and growth differentiation factor-15 were found to be nega-tively regulated, while, S100, calcium-binding protein A9 and angiomotin-like-2 were positively regulated in GLCs of women with PCOS. Comparing our data with previously published relevant transcriptomic studies showed metabolic, cytokine-cytokine receptor interaction, IL-17, and chemokine signalling pathways were most commonly affected in PCOS. Overall, this data can provide insights into mechanisms contributing to PCOS pathophysiology and can be explored as potential indicators for oocyte/embryo quality in IVF settings.

Automated summary

Polycystic ovary syndrome (PCOS) is a complex disorder with reproductive and metabolic consequences. By analyzing the transcriptomic profiles of granulosa-lutein cells (GLCs), we identified differential expression of 876 genes in GLCs between PCOS and controls, involving various processes related to folliculogenesis, oocyte development, and maturation. Metabolic dysregulation and oxidative stress may impair oocyte development and quality in PCOS.