Sex-specific effects of prenatal bisphenol A exposure on transcriptome-interactome profiles of autism candidate genes in neural stem cells from offspring hippocampus

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.
Surangrat Thongkorn, Department of Biotechnology and Biomedicine (DTU Bioengineering), Technical University of Denmark, 2800, Kgs. Lyngby, Denmark.
Songphon Kanlayaprasit, Chulalongkorn Autism Research and Innovation Center of Excellence (Chula ACE), Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, 154 Soi Chula 12, Rama 1 Road, Wangmai, Pathumwan, Bangkok, 10330, Thailand.
Thanit Saeliw, Chulalongkorn Autism Research and Innovation Center of Excellence (Chula ACE), Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, 154 Soi Chula 12, Rama 1 Road, Wangmai, Pathumwan, 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.
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.
Depicha Jindatip, Chulalongkorn Autism Research and Innovation Center of Excellence (Chula ACE), Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, 154 Soi Chula 12, Rama 1 Road, Wangmai, Pathumwan, Bangkok, 10330, Thailand.
Valerie W. Hu, Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, 20052, USA.
Takako Kikkawa, Department of Developmental Neuroscience, United Centers for Advanced Research and Translational Medicine (ART), Tohoku University Graduate School of Medicine, Sendai, Miyagi, 980-8577, Japan.
Noriko Osumi, Department of Developmental Neuroscience, United Centers for Advanced Research and Translational Medicine (ART), Tohoku University Graduate School of Medicine, Sendai, Miyagi, 980-8577, Japan.
Tewarit Sarachana, Chulalongkorn Autism Research and Innovation Center of Excellence (Chula ACE), Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, 154 Soi Chula 12, Rama 1 Road, Wangmai, Pathumwan, Bangkok, 10330, Thailand. tewarit.sa@chula.ac.th.

Document Type

Journal Article

Publication Date

1-22-2025

Journal

Scientific reports

Volume

15

Issue

1

DOI

10.1038/s41598-025-86392-2

Keywords

Autism spectrum disorder; Bisphenol A; Endocrine-disrupting chemical; Hippocampus; Interactome; Neural stem cells; Sex difference; Transcriptome

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.

Department

Biochemistry and Molecular Medicine

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