Prenatal exposure to bisphenol A disrupts RNA splicing in the prefrontal cortex and promotes behaviors related to autism in offspring

Authors

• Pawinee Panjabud, The Ph.D. Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.
• Songphon Kanlayaprasit, Chulalongkorn Autism Research and Innovation Center of Excellence (ChulaACE), Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.
• Surangrat Thongkorn, Department of Biotechnology and Biomedicine (DTU), Technical University of Denmark, Lyngby, 2800, Denmark.
• Kwanjira Songsritaya, The M.Sc. Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.
• Pattanachat Lertpeerapan, The Ph.D. Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.
• Kasidit Kasitipradit, The Ph.D. Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.
• Thanawin Jantheang, The Ph.D. Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.
• Suthathip Sarobol, Department of Laboratory Medicine, King Chulalongkorn Memorial Hospital, Bangkok, 10330, Thailand.
• Thanit Saeliw, Chulalongkorn Autism Research and Innovation Center of Excellence (ChulaACE), Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.
• Valerie W. Hu, Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, 20037, USA.
• Takeshi Imai, Department of Developmental Neurophysiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
• Tewarit Sarachana, Chulalongkorn Autism Research and Innovation Center of Excellence (ChulaACE), Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, 10330, Thailand. tewarit.sa@chula.ac.th.

Document Type

Journal Article

Publication Date

7-17-2025

Journal

Scientific reports

Volume

15

Issue

1

DOI

10.1038/s41598-025-09909-9

Keywords

Alternative splicing; Autism spectrum disorder; Autism-related behavior; Bisphenol A; Prefrontal cortex; Prenatal exposure

Abstract

Prenatal exposure to bisphenol A (BPA), a common endocrine disruptor, has been increasingly implicated in neurodevelopmental disorders, including autism spectrum disorder. This study explores the molecular mechanisms by which prenatal BPA exposure affects alternative RNA splicing in the prefrontal cortex and investigates the potential link between alternative RNA splicing and autism-related behaviors in rat offspring. Using RNA sequencing and high-resolution melting real-time PCR, we identified differentially alternative splicing events associated with autism candidate genes. Gene ontology and pathway analyses revealed significant enrichment of differentially alternative splicing genes and neurological pathways relevant to autism. BPA appears to act through autism-related transcription factors, affecting RNA-binding proteins. Altered expressions of these RNA-binding proteins influenced alternative RNA splicing events within key autism-related genes, implicating them in disrupted synaptogenesis. Behavioral analyses of offspring exposed to BPA revealed autism-associated traits, including hyperactivity, anxiety, and aggression, which correlated with the observed sex-specific alternative RNA splicing patterns. These findings suggest that BPA-induced alterations of transcription factors and RNA-binding proteins affect alternative RNA splicing and synaptic development, potentially contributing to autism pathophysiology. This research underscores the role of environmental factors in autism etiology and highlights the importance of awareness and preventive measures against prenatal BPA exposure.

APA Citation

Panjabud, Pawinee; Kanlayaprasit, Songphon; Thongkorn, Surangrat; Songsritaya, Kwanjira; Lertpeerapan, Pattanachat; Kasitipradit, Kasidit; Jantheang, Thanawin; Sarobol, Suthathip; Saeliw, Thanit; Hu, Valerie W.; Imai, Takeshi; and Sarachana, Tewarit, "Prenatal exposure to bisphenol A disrupts RNA splicing in the prefrontal cortex and promotes behaviors related to autism in offspring" (2025). GW Authored Works. Paper 7573.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/7573

Department

Biochemistry and Molecular Medicine