Autism-Related Transcription Factors Underlying the Sex-Specific Effects of Prenatal Bisphenol A Exposure on Transcriptome-Interactome Profiles in the Offspring Prefrontal Cortex
Bisphenol A (BPA) is an environmental risk factor for autism spectrum disorder (ASD). BPA exposure dysregulates ASD-related genes in the hippocampus and neurological functions of offspring. However, whether prenatal BPA exposure has an impact on genes in the prefrontal cortex, another brain region h...
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MDPI AG
2021-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/24/13201 |
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| author | Songphon Kanlayaprasit Surangrat Thongkorn Pawinee Panjabud Depicha Jindatip Valerie W. Hu Takako Kikkawa Noriko Osumi Tewarit Sarachana |
| author_facet | Songphon Kanlayaprasit Surangrat Thongkorn Pawinee Panjabud Depicha Jindatip Valerie W. Hu Takako Kikkawa Noriko Osumi Tewarit Sarachana |
| author_sort | Songphon Kanlayaprasit |
| collection | DOAJ |
| description | Bisphenol A (BPA) is an environmental risk factor for autism spectrum disorder (ASD). BPA exposure dysregulates ASD-related genes in the hippocampus and neurological functions of offspring. However, whether prenatal BPA exposure has an impact on genes in the prefrontal cortex, another brain region highly implicated in ASD, and through what mechanisms have not been investigated. Here, we demonstrated that prenatal BPA exposure disrupts the transcriptome–interactome profiles of the prefrontal cortex of neonatal rats. Interestingly, the list of BPA-responsive genes was significantly enriched with known ASD candidate genes, as well as genes that were dysregulated in the postmortem brain tissues of ASD cases from multiple independent studies. Moreover, several differentially expressed genes in the offspring’s prefrontal cortex were the targets of ASD-related transcription factors, including AR, ESR1, and RORA. The hypergeometric distribution analysis revealed that BPA may regulate the expression of such genes through these transcription factors in a sex-dependent manner. The molecular docking analysis of BPA and ASD-related transcription factors revealed novel potential targets of BPA, including RORA, SOX5, TCF4, and YY1. Our findings indicated that prenatal BPA exposure disrupts ASD-related genes in the offspring’s prefrontal cortex and may increase the risk of ASD through sex-dependent molecular mechanisms, which should be investigated further. |
| first_indexed | 2024-03-10T03:57:41Z |
| format | Article |
| id | doaj.art-9f1c7f1fa60d43268e510c8a3ec16408 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:57:41Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9f1c7f1fa60d43268e510c8a3ec164082023-11-23T08:42:44ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-0122241320110.3390/ijms222413201Autism-Related Transcription Factors Underlying the Sex-Specific Effects of Prenatal Bisphenol A Exposure on Transcriptome-Interactome Profiles in the Offspring Prefrontal CortexSongphon Kanlayaprasit0Surangrat Thongkorn1Pawinee Panjabud2Depicha Jindatip3Valerie W. Hu4Takako Kikkawa5Noriko Osumi6Tewarit Sarachana7The Ph.D. Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, ThailandThe Ph.D. Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, ThailandThe Ph.D. Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, ThailandSystems Neuroscience of Autism and PSychiatric Disorders (SYNAPS) Research Unit, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20052, USADepartment of Developmental Neuroscience, United Centers for Advanced Research and Translational Medicine (ART), Tohoku University Graduate School of Medicine, Sendai 980-8577, Miyagi, JapanDepartment of Developmental Neuroscience, United Centers for Advanced Research and Translational Medicine (ART), Tohoku University Graduate School of Medicine, Sendai 980-8577, Miyagi, JapanSystems Neuroscience of Autism and PSychiatric Disorders (SYNAPS) Research Unit, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, ThailandBisphenol A (BPA) is an environmental risk factor for autism spectrum disorder (ASD). BPA exposure dysregulates ASD-related genes in the hippocampus and neurological functions of offspring. However, whether prenatal BPA exposure has an impact on genes in the prefrontal cortex, another brain region highly implicated in ASD, and through what mechanisms have not been investigated. Here, we demonstrated that prenatal BPA exposure disrupts the transcriptome–interactome profiles of the prefrontal cortex of neonatal rats. Interestingly, the list of BPA-responsive genes was significantly enriched with known ASD candidate genes, as well as genes that were dysregulated in the postmortem brain tissues of ASD cases from multiple independent studies. Moreover, several differentially expressed genes in the offspring’s prefrontal cortex were the targets of ASD-related transcription factors, including AR, ESR1, and RORA. The hypergeometric distribution analysis revealed that BPA may regulate the expression of such genes through these transcription factors in a sex-dependent manner. The molecular docking analysis of BPA and ASD-related transcription factors revealed novel potential targets of BPA, including RORA, SOX5, TCF4, and YY1. Our findings indicated that prenatal BPA exposure disrupts ASD-related genes in the offspring’s prefrontal cortex and may increase the risk of ASD through sex-dependent molecular mechanisms, which should be investigated further.https://www.mdpi.com/1422-0067/22/24/13201endocrine-disrupting chemicalbisphenol Aprenatal exposureautism spectrum disordersex differencestranscription factor |
| spellingShingle | Songphon Kanlayaprasit Surangrat Thongkorn Pawinee Panjabud Depicha Jindatip Valerie W. Hu Takako Kikkawa Noriko Osumi Tewarit Sarachana Autism-Related Transcription Factors Underlying the Sex-Specific Effects of Prenatal Bisphenol A Exposure on Transcriptome-Interactome Profiles in the Offspring Prefrontal Cortex International Journal of Molecular Sciences endocrine-disrupting chemical bisphenol A prenatal exposure autism spectrum disorder sex differences transcription factor |
| title | Autism-Related Transcription Factors Underlying the Sex-Specific Effects of Prenatal Bisphenol A Exposure on Transcriptome-Interactome Profiles in the Offspring Prefrontal Cortex |
| title_full | Autism-Related Transcription Factors Underlying the Sex-Specific Effects of Prenatal Bisphenol A Exposure on Transcriptome-Interactome Profiles in the Offspring Prefrontal Cortex |
| title_fullStr | Autism-Related Transcription Factors Underlying the Sex-Specific Effects of Prenatal Bisphenol A Exposure on Transcriptome-Interactome Profiles in the Offspring Prefrontal Cortex |
| title_full_unstemmed | Autism-Related Transcription Factors Underlying the Sex-Specific Effects of Prenatal Bisphenol A Exposure on Transcriptome-Interactome Profiles in the Offspring Prefrontal Cortex |
| title_short | Autism-Related Transcription Factors Underlying the Sex-Specific Effects of Prenatal Bisphenol A Exposure on Transcriptome-Interactome Profiles in the Offspring Prefrontal Cortex |
| title_sort | autism related transcription factors underlying the sex specific effects of prenatal bisphenol a exposure on transcriptome interactome profiles in the offspring prefrontal cortex |
| topic | endocrine-disrupting chemical bisphenol A prenatal exposure autism spectrum disorder sex differences transcription factor |
| url | https://www.mdpi.com/1422-0067/22/24/13201 |
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