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

## TL;DR

This study explores how alternative splicing of transcription factors contributes to the development of polycystic ovary syndrome (PCOS), identifying key splicing events that may lead to new diagnostic or therapeutic approaches.

## Contribution

The study identifies novel alternative splicing events in transcription factors, particularly in Nfkb1, which may contribute to PCOS pathogenesis.

## Key findings

- 42 differentially spliced transcription factors were identified in PCOS, enriched in transcriptional regulation and metabolic pathways.
- Nfkb1 and Nfkb2 were significantly upregulated in a PCOS mouse model, with a specific exon-skipping event in Nfkb1 (Nfkb1-ES1496).
- Altered splicing of transcription factors implicates dysregulated NF-κB signaling in PCOS pathogenesis.

## Abstract

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.