Prenatal exposure to bisphenol A disrupts RNA splicing in the prefrontal cortex and promotes behaviors related to autism in offspring
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 pre...
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-09909-9 |
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| author | Pawinee Panjabud Songphon Kanlayaprasit Surangrat Thongkorn Kwanjira Songsritaya Pattanachat Lertpeerapan Kasidit Kasitipradit Thanawin Jantheang Suthathip Sarobol Thanit Saeliw Valerie W. Hu Takeshi Imai Tewarit Sarachana |
| author_facet | Pawinee Panjabud Songphon Kanlayaprasit Surangrat Thongkorn Kwanjira Songsritaya Pattanachat Lertpeerapan Kasidit Kasitipradit Thanawin Jantheang Suthathip Sarobol Thanit Saeliw Valerie W. Hu Takeshi Imai Tewarit Sarachana |
| author_sort | Pawinee Panjabud |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d473f2b64c264e0888d4c9c6ff8f4036 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-d473f2b64c264e0888d4c9c6ff8f40362025-08-20T03:05:21ZengNature PortfolioScientific Reports2045-23222025-07-0115112410.1038/s41598-025-09909-9Prenatal exposure to bisphenol A disrupts RNA splicing in the prefrontal cortex and promotes behaviors related to autism in offspringPawinee Panjabud0Songphon Kanlayaprasit1Surangrat Thongkorn2Kwanjira Songsritaya3Pattanachat Lertpeerapan4Kasidit Kasitipradit5Thanawin Jantheang6Suthathip Sarobol7Thanit Saeliw8Valerie W. Hu9Takeshi Imai10Tewarit Sarachana11The Ph.D. Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn UniversityChulalongkorn Autism Research and Innovation Center of Excellence (ChulaACE), Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn UniversityDepartment of Biotechnology and Biomedicine (DTU), Technical University of DenmarkThe M.Sc. Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn UniversityThe Ph.D. Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn UniversityThe Ph.D. Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn UniversityThe Ph.D. Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn UniversityDepartment of Laboratory Medicine, King Chulalongkorn Memorial HospitalChulalongkorn Autism Research and Innovation Center of Excellence (ChulaACE), Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn UniversityDepartment of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington UniversityDepartment of Developmental Neurophysiology, Graduate School of Medical Sciences, Kyushu UniversityChulalongkorn Autism Research and Innovation Center of Excellence (ChulaACE), Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn UniversityAbstract 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.https://doi.org/10.1038/s41598-025-09909-9Autism spectrum disorderAlternative splicingBisphenol APrefrontal cortexAutism-related behaviorPrenatal exposure |
| spellingShingle | Pawinee Panjabud Songphon Kanlayaprasit Surangrat Thongkorn Kwanjira Songsritaya Pattanachat Lertpeerapan Kasidit Kasitipradit Thanawin Jantheang Suthathip Sarobol Thanit Saeliw Valerie W. Hu Takeshi Imai Tewarit Sarachana Prenatal exposure to bisphenol A disrupts RNA splicing in the prefrontal cortex and promotes behaviors related to autism in offspring Scientific Reports Autism spectrum disorder Alternative splicing Bisphenol A Prefrontal cortex Autism-related behavior Prenatal exposure |
| title | Prenatal exposure to bisphenol A disrupts RNA splicing in the prefrontal cortex and promotes behaviors related to autism in offspring |
| title_full | Prenatal exposure to bisphenol A disrupts RNA splicing in the prefrontal cortex and promotes behaviors related to autism in offspring |
| title_fullStr | Prenatal exposure to bisphenol A disrupts RNA splicing in the prefrontal cortex and promotes behaviors related to autism in offspring |
| title_full_unstemmed | Prenatal exposure to bisphenol A disrupts RNA splicing in the prefrontal cortex and promotes behaviors related to autism in offspring |
| title_short | Prenatal exposure to bisphenol A disrupts RNA splicing in the prefrontal cortex and promotes behaviors related to autism in offspring |
| title_sort | prenatal exposure to bisphenol a disrupts rna splicing in the prefrontal cortex and promotes behaviors related to autism in offspring |
| topic | Autism spectrum disorder Alternative splicing Bisphenol A Prefrontal cortex Autism-related behavior Prenatal exposure |
| url | https://doi.org/10.1038/s41598-025-09909-9 |
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