Placental Alterations in Autism Spectrum Disorder: An In Silico Approach to circRNA-miRNA-mRNA Networks.

Scientists used computer analysis to study how the placenta might be connected to autism. They found special molecules called circular RNAs in the placenta that control genes linked to autism. These molecules affect important processes like immune function and brain development. The research identified five specific genes that appear important for both placenta development and autism. This suggests problems in the placenta during pregnancy might contribute to autism development.

This bioinformatics study investigated the role of circular RNA (circRNA) in linking placental alterations to autism spectrum disorder (ASD). Using computational analysis tools, researchers mapped interactions between circRNA, microRNA, and messenger RNA networks. They identified 71 circRNAs linked to ASD and 30 highly expressed in placenta, which regulate critical pathways including immune response, gene transcription, and ASD-associated Notch and AKT signalling. The analysis revealed five shared genes (SRSF11, PSMD11, NOTCH1, CREBBP, TBL1X) between ASD and placental groups, with specific circRNA-miRNA interactions identified.

The findings suggest placental circRNAs may play important epigenetic roles in ASD development through posttranscriptional regulation of gene expression networks critical for both placental development and autism aetiology.

While preliminary, this research identifies potential biomarkers and therapeutic targets linking placental function to ASD. The circRNA-miRNA-mRNA networks could inform future prenatal screening approaches and guide research into early intervention strategies. However, experimental validation is essential before clinical applications.

This is a purely computational study using bioinformatics tools without experimental validation. No actual placental tissue or clinical samples were analyzed. The findings require laboratory confirmation and clinical validation to establish real-world relevance.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication and repetitive behaviours with an aetiology involving genetic and environmental risk factors. Placental alterations, such as epigenetic DNA methylation and structural abnormalities, have been associated with ASD. Circular RNA (circRNA), covalently closed and highly stable molecules, play an epigenetic role by sequestering microRNA (miRNA) and modulating messenger RNA (mRNA) translation, forming posttranscriptional networks essential for gene expression. However, there is a lack of evidence in the literature regarding the involvement of circRNA, the placenta and ASD.

To address this gap, the study aimed to map the interactions among circRNA, miRNA and mRNA, investigating their relevance to ASD and placental development using bioinformatics tools, such as circATLAS and miRTargetLink 2.0. The analysis identified 71 circRNA linked to ASD and 30 highly expressed in the placenta, which regulate pathways such as 'immune response,' 'gene transcription,' and 'replication,' and others previously associated with ASD, such as 'Notch and AKT signalling pathway'. Searches in the SFARI database revealed 11 relevant genes in the ASD group, nine in the placenta group and five shared genes (SRSF11, PSMD11, NOTCH1, CREBBP and TBL1X). Further analysis identified the interaction of the circRNA hsa-MAN1A2_0008 with miRNA associated with these genes.

These findings suggest that highly expressed circRNA in the placenta regulate critical pathways for placental development and ASD aetiology, underscoring their role in linking placental alterations to ASD.