Deciphering the molecular connections between polycystic ovarian syndrome and autism spectrum disorder using...

Epidemiological studies show a positive association between polycystic ovarian syndrome (PCOS) and autism spectrum disorder (ASD), potentially due to elevated prenatal testosterone levels, supporting the prenatal sex steroid theory. However, the molecular mechanisms behind this association remain unclear. This study investigates the association between PCOS and ASD by identifying shared hub genes and exploring molecular mechanisms using publicly available gene expression datasets (GSE1615, GSE5850, GSE10946, GSE80432, and GSE28521). We analysed these datasets for identifying differentially expressed genes (DEGs) and pathways using bioinformatic tools such as GEO2R, STRING, Enrichr, and Cytoscape. Sixty-three overlapping DEGs were identified, along with shared pathways related to hormone receptor signalling, synaptic function, and metabolic regulation. Network analysis highlighted hub genes (TP53, MAPK1, MAPK14, AR, ESR1, CCND1, EP300), regulatory microRNAs and transcription factors with potential roles in both disorders. Drug signature enrichment via DSigDB identified candidate small molecules through hypothesis generating prediction, including celecoxib, N-acetylcysteine and other drug molecules. Elevated maternal androgens are proposed as a shared environmental factor that may interact with molecularly regulated pathways, contributing to the observed molecular convergence. While the study integrates multiple well-curated datasets, sample sizes were modest, and analysis were performed exclusively in silico without experimental validation. These findings provide insight into the potential mechanistic overlap between PCOS and ASD, highlighting the molecular targets for future functional and translational studies, while underscoring the need for careful interpretation in maternal-fetal health contexts.