The landscape of alternative splicing in granulosa cells and a potential novel role of YAP1 in PCOS

Polycystic ovary syndrome (PCOS) is a prevalent yet complex reproductive endocrine disorder affecting 11-13% of women worldwide. Its main symptoms include elevated androgen levels, irregular menstrual cycles, and long-term metabolic and offspring health implications. Despite the disease's multifaceted nature involving genetic, epigenetic, and environmental factors, the role of alternative splicing in ovarian granulosa cells remains relatively unexplored. This study aims to investigate the transcriptional and alternative splicing characteristics of granulosa cells in PCOS patients and to elucidate the potential functional consequences of these changes. Analysis of previous published transcriptome sequencing data identified 491 upregulated and 401 downregulated genes in granulosa cells of PCOS patients, significantly involved in immune-related processes. Additionally, 1250 differential splicing events, predominantly involving exon skipping and affecting 947 genes, were detected. These genes with alternative splicing patterns were found to be enriched in endoplasmic reticulum stress and protein post-translational modification processes, suggesting their role in PCOS pathology. Moreover, the study highlighted that the utilization of different splice isoforms of the YAP1 gene may impact its interaction in the Hippo signaling pathway, influencing the pathogenesis of PCOS. These findings underscore substantial alterations in alternative splicing in granulosa cells of PCOS patients, providing a novel viewpoint for comprehending the molecular underpinnings of PCOS and suggesting potential avenues for therapeutic intervention.