Sex-specific effects of prenatal bisphenol A exposure on transcriptome-interactome profiles of autism candidate genes in neural stem cells from offspring hippocampus
Abstract Bisphenol A (BPA), an endocrine-disrupting chemical, is increasingly linked to the pathogenesis of autism spectrum disorder (ASD). This study investigates the effects of prenatal BPA exposure on neural stem cells (NSCs) from the hippocampi of rat offspring, a brain region critical for neuro...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-025-86392-2 |
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| author | Kasidit Kasitipradit Surangrat Thongkorn Songphon Kanlayaprasit Thanit Saeliw Pattanachat Lertpeerapan Pawinee Panjabud Depicha Jindatip Valerie W. Hu Takako Kikkawa Noriko Osumi Tewarit Sarachana |
| author_facet | Kasidit Kasitipradit Surangrat Thongkorn Songphon Kanlayaprasit Thanit Saeliw Pattanachat Lertpeerapan Pawinee Panjabud Depicha Jindatip Valerie W. Hu Takako Kikkawa Noriko Osumi Tewarit Sarachana |
| author_sort | Kasidit Kasitipradit |
| collection | DOAJ |
| description | Abstract Bisphenol A (BPA), an endocrine-disrupting chemical, is increasingly linked to the pathogenesis of autism spectrum disorder (ASD). This study investigates the effects of prenatal BPA exposure on neural stem cells (NSCs) from the hippocampi of rat offspring, a brain region critical for neurodevelopment and implicated in ASD. Pregnant rats were administered with BPA or vehicle control once daily via oral gavage from gestational day 1 until parturition. NSCs were isolated from the offspring’s hippocampi on postnatal day 1, and RNA sequencing was performed to examine transcriptomic alterations. Differentially expressed genes (DEGs) were identified through RNA-seq and further analyzed using Ingenuity Pathway Analysis (IPA) to explore disrupted pathways. In addition, in vitro proliferation assays were conducted, utilizing immunofluorescence staining for Sox2, a stem cell marker, and BrdU to quantify proliferating NSCs. Our results revealed that prenatal BPA exposure induced sex-specific alterations in NSC gene expression, with ASD-related genes such as Atp1a3, Nefl, and Grin1 being particularly dysregulated in male offspring. Moreover, sex-specific changes in NSC proliferation were observed. The study underscores BPA’s potential as an environmental risk factor for ASD, emphasizing the need for further research into its role in sex-specific neurodevelopmental effects. |
| format | Article |
| id | doaj-art-968896b8725f46b0837c7c7b4e63fb25 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-968896b8725f46b0837c7c7b4e63fb252025-01-26T12:32:22ZengNature PortfolioScientific Reports2045-23222025-01-0115112310.1038/s41598-025-86392-2Sex-specific effects of prenatal bisphenol A exposure on transcriptome-interactome profiles of autism candidate genes in neural stem cells from offspring hippocampusKasidit Kasitipradit0Surangrat Thongkorn1Songphon Kanlayaprasit2Thanit Saeliw3Pattanachat Lertpeerapan4Pawinee Panjabud5Depicha Jindatip6Valerie W. Hu7Takako Kikkawa8Noriko Osumi9Tewarit Sarachana10The Ph.D. Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn UniversityDepartment of Biotechnology and Biomedicine (DTU Bioengineering), Technical University of DenmarkChulalongkorn Autism Research and Innovation Center of Excellence (Chula ACE), Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn UniversityChulalongkorn Autism Research and Innovation Center of Excellence (Chula ACE), 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 UniversityChulalongkorn Autism Research and Innovation Center of Excellence (Chula ACE), 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 Neuroscience, United Centers for Advanced Research and Translational Medicine (ART), Tohoku University Graduate School of MedicineDepartment of Developmental Neuroscience, United Centers for Advanced Research and Translational Medicine (ART), Tohoku University Graduate School of MedicineChulalongkorn Autism Research and Innovation Center of Excellence (Chula ACE), Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn UniversityAbstract Bisphenol A (BPA), an endocrine-disrupting chemical, is increasingly linked to the pathogenesis of autism spectrum disorder (ASD). This study investigates the effects of prenatal BPA exposure on neural stem cells (NSCs) from the hippocampi of rat offspring, a brain region critical for neurodevelopment and implicated in ASD. Pregnant rats were administered with BPA or vehicle control once daily via oral gavage from gestational day 1 until parturition. NSCs were isolated from the offspring’s hippocampi on postnatal day 1, and RNA sequencing was performed to examine transcriptomic alterations. Differentially expressed genes (DEGs) were identified through RNA-seq and further analyzed using Ingenuity Pathway Analysis (IPA) to explore disrupted pathways. In addition, in vitro proliferation assays were conducted, utilizing immunofluorescence staining for Sox2, a stem cell marker, and BrdU to quantify proliferating NSCs. Our results revealed that prenatal BPA exposure induced sex-specific alterations in NSC gene expression, with ASD-related genes such as Atp1a3, Nefl, and Grin1 being particularly dysregulated in male offspring. Moreover, sex-specific changes in NSC proliferation were observed. The study underscores BPA’s potential as an environmental risk factor for ASD, emphasizing the need for further research into its role in sex-specific neurodevelopmental effects.https://doi.org/10.1038/s41598-025-86392-2Autism spectrum disorderBisphenol AEndocrine-disrupting chemicalTranscriptomeInteractomeNeural stem cells |
| spellingShingle | Kasidit Kasitipradit Surangrat Thongkorn Songphon Kanlayaprasit Thanit Saeliw Pattanachat Lertpeerapan Pawinee Panjabud Depicha Jindatip Valerie W. Hu Takako Kikkawa Noriko Osumi Tewarit Sarachana Sex-specific effects of prenatal bisphenol A exposure on transcriptome-interactome profiles of autism candidate genes in neural stem cells from offspring hippocampus Scientific Reports Autism spectrum disorder Bisphenol A Endocrine-disrupting chemical Transcriptome Interactome Neural stem cells |
| title | Sex-specific effects of prenatal bisphenol A exposure on transcriptome-interactome profiles of autism candidate genes in neural stem cells from offspring hippocampus |
| title_full | Sex-specific effects of prenatal bisphenol A exposure on transcriptome-interactome profiles of autism candidate genes in neural stem cells from offspring hippocampus |
| title_fullStr | Sex-specific effects of prenatal bisphenol A exposure on transcriptome-interactome profiles of autism candidate genes in neural stem cells from offspring hippocampus |
| title_full_unstemmed | Sex-specific effects of prenatal bisphenol A exposure on transcriptome-interactome profiles of autism candidate genes in neural stem cells from offspring hippocampus |
| title_short | Sex-specific effects of prenatal bisphenol A exposure on transcriptome-interactome profiles of autism candidate genes in neural stem cells from offspring hippocampus |
| title_sort | sex specific effects of prenatal bisphenol a exposure on transcriptome interactome profiles of autism candidate genes in neural stem cells from offspring hippocampus |
| topic | Autism spectrum disorder Bisphenol A Endocrine-disrupting chemical Transcriptome Interactome Neural stem cells |
| url | https://doi.org/10.1038/s41598-025-86392-2 |
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