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

Brayan Braz-Barbosa1,2,3,4, Carmem Gottfried1,2,3,4, Júlio Santos-Terra1,2,3,4

  • 1Translational Research Group in Autism Spectrum Disorder-GETTEA, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.

International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience
|November 11, 2025
PubMed
Summary

Circular RNAs (circRNAs) in the placenta are linked to autism spectrum disorder (ASD) risk. These molecules regulate key pathways involved in both placental development and ASD etiology, suggesting a connection between placental issues and ASD.

Keywords:
ASDbioinformaticscircRNAcircRNA–miRNA–mRNAplacenta

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Area of Science:

  • Neuroscience
  • Genetics
  • Developmental Biology

Background:

  • Autism spectrum disorder (ASD) is a neurodevelopmental condition with complex genetic and environmental factors.
  • Placental abnormalities, including epigenetic changes and structural issues, are increasingly associated with ASD.
  • Circular RNAs (circRNAs) are stable molecules involved in epigenetic regulation via microRNA (miRNA) and messenger RNA (mRNA) interactions, but their role in ASD and the placenta is understudied.

Purpose of the Study:

  • To investigate the interactions among circRNAs, miRNAs, and mRNAs relevant to ASD and placental development.
  • To identify circRNAs associated with ASD and those highly expressed in the placenta.
  • To explore the potential role of circRNAs in linking placental alterations to ASD etiology.

Main Methods:

  • Utilized bioinformatics tools, including circATLAS and miRTargetLink 2.0, for network analysis.
  • Analyzed circRNA, miRNA, and mRNA interactions.
  • Cross-referenced identified genes with the SFARI database for ASD relevance.

Main Results:

  • Identified 71 circRNAs associated with ASD and 30 highly expressed in the placenta.
  • Discovered that these circRNAs regulate pathways like 'immune response,' 'gene transcription,' 'replication,' and 'Notch and AKT signalling pathway'.
  • Found five shared genes (SRSF11, PSMD11, NOTCH1, CREBBP, TBL1X) between ASD and placental groups, with specific circRNA-miRNA interactions identified.

Conclusions:

  • Highly expressed placental circRNAs play a role in regulating pathways critical for both placental development and ASD.
  • circRNAs may serve as a molecular link between placental abnormalities and the development of ASD.
  • These findings highlight circRNAs as potential biomarkers or therapeutic targets for ASD.