Rna analysis of the regulation of expression and alternative splicing in polycystic ovarian syndrome

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder whose pathophysiological mechanisms remain incompletely understood. Alternative splicing of transcription factors (TFs) may lead to significant functional consequences in the pathogenesis of PCOS. This study investigated genome-wide AS patterns and the expression of key TFs in PCOS to identify functionally relevant splicing events in a human dataset and validate them in a mouse model. Bioinformatics analysis of a PCOS RNA-seq dataset revealed 42 differentially spliced TFs, with enrichment in transcriptional regulation and metabolic pathways. Subsequent validation in a PCOS mouse model highlighted significant upregulation of Nfkb1 and Nfkb2, along with a specific exon-skipping event in Nfkb1 ;(Nfkb1-ES1496). Our findings demonstrate altered AS of critical TFs in PCOS, implicating dysregulated NF-κB signalling through splicing modulation as a potential contributor to the disorder, which may offer novel biomarker or therapeutic avenues.