Polycystic ovary syndrome (PCOS) is a complex heterogeneous disorder with reproductive and metabolic consequences 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 metabolites to the growing oocyte, affecting oocyte development and competence. Additionally, high metabolic activity 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 environment. Among the validated genes, prokineticin-1 and growth differentiation factor-15 were found to be negatively 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.

多囊卵巢综合征（PCOS）是一种复杂的异质性疾病，会影响生殖和代谢，其病因仍不清楚。为了了解可能控制 PCOS 女性卵泡缺陷的细胞机制，我们通过 RNA-Seq 分析对颗粒叶黄素细胞 (GLC)进行了转录组分析。我们发现 PCOS 和对照之间 GLC 中 876 个基因存在差异表达，这些基因属于支持卵泡发生、卵母细胞发育和成熟的各种过程，如细胞周期、细胞外基质组织、血管生成、氧化应激、代谢等。卵母细胞和 GLC 之间的串扰是决定卵母细胞质量的基本基石，高度相互关联的代谢和氧化还原稳态途径可能会影响这一点。我们发现一些参与碳水化合物、核苷酸、胆固醇和脂质代谢的基因失调，这可能会损害生长中卵母细胞的代谢物供应，影响卵母细胞的发育和能力。此外，如果不平衡，卵泡发生期间的高代谢活动可能会增加对细胞和大分子的氧化损伤。我们观察到卵泡环境中氧化还原稳态和 AGE-RAGE 信号传导的失调。在经验证的基因中，PCOS 女性 GLC 中，prokineticin-1 和生长分化因子 15 呈负向调节，而 S100、钙结合蛋白 A9 和血管动蛋白样 2 呈正向调节。将我们的数据与之前发表的相关转录组研究进行比较表明，代谢、细胞因子-细胞因子受体相互作用、IL-17 和趋化因子信号通路在 PCOS 中最常受到影响。总体而言，这些数据可以深入了解 PCOS病理生理学机制，并可作为 IVF 环境中卵母细胞/胚胎质量的潜在指标进行探索。