Polycystic ovarian syndrome (PCOS) is a neuroendocrine disorder represented clinically by pathological accumulation of immature and atretic follicles, enlarged ovaries, stromal hyperplasia, and hyperandrogenism (HA). It also includes insulin resistance (IR), an imbalanced ratio of luteinizing hormone (LH) to follicle-stimulating hormone (FSH). PCOS affects more than 20 % of females in their reproductive ages worldwide (Zou et al., 2022) and is a underlying cause of infertility in females (Batóg et al., 2023; Fernandez et al., 2011). Autism spectrum disorder (ASD) is a complex condition marked by repetitive behavioral patterns, difficulties in social communication, linguistic impairments and restricted interest evident in early life (Henderson et al., 2017; Lord et al., 2020). Although PCOS and ASD exhibit unique clinical features, recent studies suggest shared etiology and pathophysiology including a molecular association between both disease conditions (R. Hu et al., 2024; Jiang et al., 2021; Nudel et al., 2022). Moreover, the children born to PCOS women may have somatic and neurodevelopmental complications due to a suboptimal intrauterine environment (Palomba et al., 2015; Hales and Barker, 2001; Kovacs-Nagy et al., 2013) which consequently elevates the risk of ASD in the progeny of PCOS mothers (Jiang et al., 2021). Prenatal hyperandrogenism is a primary hallmark of PCOS, postulated to be linked to neurodevelopmental disorders in offsprings (Baron-Cohen et al., 2011; Cesta et al., 2020). Large genome-wide association studies revealed three signalling networks associated with ASD, i.e., synaptic function, steroidogenesis, and neurite overgrowth (Poelmans et al., 2013). Various genetic studies have found an association between genetic polymorphisms and the development of ASD among children (Lakatošová et al., 2022). The epidemiological studies have shown a positive association between fetal androgen exposure and ASD (Palm et al., 2023), also a corelation has been reported between maternal hyperandrogenic condition in PCOS leading to ASD in progeny (Rotem et al., 2021). Despite of substantial research in the field, there is a limited understanding of the specific shared molecular pathways associated with PCOS and ASD. Moreover, the studies so far do not comprehensively explore gene-environment interactions contributing to both conditions. The utilization of integrated multi-omics data, network analysis, and functional validation holds significant potential in elucidating the molecular underpinnings of these disorders, hence offering novel opportunities for diagnostic and therapeutic interventions (Hossain et al., 2022).

This study serves to identify differentially expressed genes (DEGs) linked to PCOS and ASD in ovarian and brain tissues, respectively, this might provide a valuable basis for identifying potential biomarkers in PCOS-associated ASD by using a bioinformatic approach. By analysing gene expression datasets from NCBI, we identified gene set variability and common hub genes associated with PCOS and ASD by utilizing statistical methods. Additionally, we confirmed protein-protein interaction, transcriptional mechanism, and interaction of miRNA and transcription factor with hub genes. We have also investigated the molecular markers and pathways involved in the development of autism. Elucidating the molecular mechanism underlying diverse signalling pathways may contribute to the development of targeted pharmacotherapeutic strategies for the management or potential treatment of the disorder. This bioinformatic study may aid in the identification of key genes and pathways associated with the phenotype, providing a valuable insight for targeted interventions in PCOS-associated ASD pharmacotherapies.