title: High dose bisphenol A impairs hippocampal neurogenesis in female mice across generations.
abstract: Bisphenol A (BPA) is used as a monomer during the manufacture of polycarbonate plastics and epoxy resins. However, BPA adversely affects reproductive organ growth and development, and it has been proposed that the detrimental effects of BPA could extend to future generations. The present study was conducted to evaluate the transgenerational effects of BPA on hippocampal neurogenesis and neurocognitive function. Pregnant female C57BL/6 mice (F0) were exposed to BPA (0.1-10 mg/kg) from gestation day 6 to 17, and female offspring (F2) from F1 generation mice were prepared. It was found that exposure of F0 mice to BPA at 10 mg/kg decreased the number of newly generated cells in the hippocampi of F2 female mice. Passive avoidance testing revealed that high-doses BPA (1 mg/kg and 10 mg/kg) decreased cross-over latency time in F2 mice, suggesting a BPA-mediated neurocognitive deficit in terms of memory retention. Furthermore, it was found that levels of phospho-ERK, brain-derived neurotrophic factor (BDNF), and phospho-CREB in hippocampi were significantly lower in F2 mice. Interestingly, the effects of BPA on hippocampal neurogenesis were found to be correlated with altered DNA methylation. In particular, high-dose BPA exposure increased DNA methylation of the CREB regulated transcription coactivator 1 (Crtc1) generated in F2 mice. These findings suggest that BPA exposure of pregnant mothers could adversely affect hippocampal neurogenesis and cognitive function in future generations by modulating the ERK and BDNF-CREB signaling cascades.
authors.affiliation: Department of Pharmacy, College of Pharmacy and Research Institute for Drug Development, Longevity Life Science and Technology Institutes, Pusan National University, Geumjeong-gu, Busan 609-735, Republic of Korea.
authors.forename: Young Jung
authors.initials: YJ
authors.lastname: Jang
authors.forename: Hee Ra
authors.initials: HR
authors.lastname: Park
authors.forename: Tae Hyung
authors.initials: TH
authors.lastname: Kim
authors.forename: Wook-Jin
authors.initials: WJ
authors.lastname: Yang
authors.forename: Jong-Joo
authors.initials: JJ
authors.lastname: Lee
authors.forename: Seon Young
authors.initials: SY
authors.lastname: Choi
authors.forename: Shin Bi
authors.initials: SB
authors.lastname: Oh
authors.forename: Eunjin
authors.initials: E
authors.lastname: Lee
authors.forename: Joo-Hong
authors.initials: JH
authors.lastname: Park
authors.forename: Hyoung-Pyo
authors.initials: HP
authors.lastname: Kim
authors.forename: Hyung Sik
authors.initials: HS
authors.lastname: Kim
authors.forename: Jaewon
authors.initials: J
authors.lastname: Lee
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003071:Cognition / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D052244:Endocrine Disruptors / Q000633:toxicity*; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D007858:Learning / Q000187:drug effects; D008431:Maternal-Fetal Exchange; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000187:drug effects*; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D052244:Endocrine Disruptors; D004968:Estrogens, Non-Steroidal; D010636:Phenols; C492004:Creb1 protein, mouse; C006780:bisphenol A; D000098826:Bisphenol A Compounds