TY - JOUR
T1 - Sex differences in the effects of prenatal bisphenol A exposure on autism-related genes and their relationships with the hippocampus functions
AU - Thongkorn, Surangrat
AU - Kanlayaprasit, Songphon
AU - Panjabud, Pawinee
AU - Saeliw, Thanit
AU - Jantheang, Thanawin
AU - Kasitipradit, Kasidit
AU - Sarobol, Suthathip
AU - Jindatip, Depicha
AU - Hu, Valerie W.
AU - Tencomnao, Tewin
AU - Kikkawa, Takako
AU - Sato, Tatsuya
AU - Osumi, Noriko
AU - Sarachana, Tewarit
N1 - Funding Information:
This study was supported by a Research Grant for New Scholars by The Thailand Research Fund and Office of the Higher Education Commission (MRG6280121) and partly supported a grant from the National Research University Project, Office of Higher Education Commission (NRU59-031-HR), and Ratchadapisek Somphot Fund for Supporting Research Unit, Chulalongkorn University (GRU 6300437001-1) to TS. The conclusions in this article were made by the authors. The Thailand Research Fund and Office of the Higher Education Commission may not necessarily agree. ST, SK, PP, TSae, TJ, and KK are graduate students in the Ph.D. Programs in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University. We wish to acknowledge Asst. Prof. Dr. Suwanakiet Sawangkoon, Asst. Prof. Dr. Anusak Kijtawornrat, Dr. Nitira Anakkul, Dr. Choopet Nitsakulthong, Ms. Sornsawan Chumjai, Ms. Saifon Sreechomphoe, and Mr. Phanupong Dungkhokkruat of the Chulalongkorn University Laboratory Animal Center for their assistance with the ethical approval process and training ST, SK, PP, TSae, KK, SS, and TS in the proper care and use of laboratory animals. We thank Ms. Bumpenporn Sanannam for her help in cryostat sectioning. We also thank Dr. Ryuichi Kimura, Department of Developmental Neuroscience, Tohoku University, Sendai, Japan, for his help with confocal immunofluorescence analysis. ST received the Royal Golden Jubilee Ph.D. Programme Scholarship (grant no. PHD/0029/2561) from the Thailand Research Fund and National Research Council of Thailand and “The 90th Anniversary Chulalongkorn University Fund (Ratchadaphiseksomphot Endowment Fund: GCUGR1125632108D-108)”, Graduate School, Chulalongkorn University. SK was financially supported by “The 90th Anniversary Chulalongkorn University Fund (Ratchadaphiseksomphot Endowment Fund: GCU-GR1125623067D-67)”, “The 100th Anniversary Chulalongkorn University Fund for Doctoral Scholarship”, and “The Overseas Research Experience Scholarship for Graduate Students from the Graduate School, Chulalongkorn University”. PP and KK were supported by “The 100th Anniversary Chulalongkorn University Fund for Doctoral Scholarship” from the Graduate School, Chulalongkorn University. KK was also supported by “The 90th Anniversary Chulalongkorn University Fund (Ratchadaphiseksomphot Endowment Fund: GCUGR1125632109D-109)”, Graduate School, Chulalongkorn University. TSae and TJ were supported by the Second Century Fund (C2F), Chulalongkorn University. Animal husbandry and housing were financially supported by Chulalongkorn University Laboratory Animal Center (CULAC) Grant (Animal Use Protocol No. 2073011) to TS and KK.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Our recent study has shown that prenatal exposure to bisphenol A (BPA) altered the expression of genes associated with autism spectrum disorder (ASD). In this study, we further investigated the effects of prenatal BPA exposure on ASD-related genes known to regulate neuronal viability, neuritogenesis, and learning/memory, and assessed these functions in the offspring of exposed pregnant rats. We found that prenatal BPA exposure increased neurite length, the number of primary neurites, and the number of neurite branches, but reduced the size of the hippocampal cell body in both sexes of the offspring. However, in utero exposure to BPA decreased the neuronal viability and the neuronal density in the hippocampus and impaired learning/memory only in the male offspring while the females were not affected. Interestingly, the expression of several ASD-related genes (e.g. Mief2, Eif3h, Cux1, and Atp8a1) in the hippocampus were dysregulated and showed a sex-specific correlation with neuronal viability, neuritogenesis, and/or learning/memory. The findings from this study suggest that prenatal BPA exposure disrupts ASD-related genes involved in neuronal viability, neuritogenesis, and learning/memory in a sex-dependent manner, and these genes may play an important role in the risk and the higher prevalence of ASD in males subjected to prenatal BPA exposure.
AB - Our recent study has shown that prenatal exposure to bisphenol A (BPA) altered the expression of genes associated with autism spectrum disorder (ASD). In this study, we further investigated the effects of prenatal BPA exposure on ASD-related genes known to regulate neuronal viability, neuritogenesis, and learning/memory, and assessed these functions in the offspring of exposed pregnant rats. We found that prenatal BPA exposure increased neurite length, the number of primary neurites, and the number of neurite branches, but reduced the size of the hippocampal cell body in both sexes of the offspring. However, in utero exposure to BPA decreased the neuronal viability and the neuronal density in the hippocampus and impaired learning/memory only in the male offspring while the females were not affected. Interestingly, the expression of several ASD-related genes (e.g. Mief2, Eif3h, Cux1, and Atp8a1) in the hippocampus were dysregulated and showed a sex-specific correlation with neuronal viability, neuritogenesis, and/or learning/memory. The findings from this study suggest that prenatal BPA exposure disrupts ASD-related genes involved in neuronal viability, neuritogenesis, and learning/memory in a sex-dependent manner, and these genes may play an important role in the risk and the higher prevalence of ASD in males subjected to prenatal BPA exposure.
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U2 - 10.1038/s41598-020-80390-2
DO - 10.1038/s41598-020-80390-2
M3 - Article
C2 - 33441873
AN - SCOPUS:85099410472
VL - 11
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 1241
ER -