Effect of Gestational Exposure to Bisphenol A on Neuronal Stem Cell Differentiation in the Neonatal Rat Hippocampus
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Purpose:Neurogenesis in neonatal period after birth occurs consequently through a series of neuronal stem/progenitor cell proliferation and differentiation. This stage is critical for determining of normal development and maturation of the brain throughout the life. Therefore, exposure to a certain physical or chemical factor(s) during pregnancy can result in serious damage in the developing brain. Bisphenol A (BPA), a plasticizer, is generally known as an endocrine disruptor exhibiting adverse effects when exposed to animals under experimental conditions. The purpose of this study was to investigate the changes in neuronal stem cell proliferation and differentiation during neonatal brain development in BPA-exposed pregnant rats. Methods:After exposure of BPA to pregnant rats, infant brains were excised at days 3, 7, and 14 after birth, and tissues were processed for histological and biochemical analyses. Results:Proliferating cell nuclear antigen (PCNA) immunostaining showed that whereas cells in the hippocampus at days 3 and 7 after birth were highly proliferating, the cells at day 14 divided less often. Immunohistochemical staining for nestin in the control group revealed that nestin-positive cells were only observed at day 3 after birth, but the immunoreactivity was not observed at day 14. In addition, glial fibrillary acidic protein (GFAP) immunoreactive cells were observed from days 7 to 14 in control tissues. However, in the BPA-exposed groups, 1) the number of PCNA- positive cells in the BPA-exposed groups at days 3 and 7 were higher than those of the control, 2) nestin-positive cells were observed at day 3 which is earlier than that of control, and 3) GFAP-positive cells were detected in the hippocampus tissue from day 3. Furthermore, western blotting showed that exposure to BPA in pregnant rats resulted in earlier expression of nestin in the neuronal rat brain compared to the controls. Conclusion:Taken together, it is assumed that precocious neurogenesis in the infant rat hippocampus might be due to BPA exposure during the gestational period. Further studies on adult brain perinatally exposed to BPA are needed to evaluate the pathological status of the hippocampus.
Abstract
Purpose:Neurogenesis in neonatal period after birth occurs consequently through a series of neuronal stem/progenitor cell proliferation and differentiation. This stage is critical for determining of normal development and maturation of the brain throughout the life. Therefore, exposure to a certain physical or chemical factor(s) during pregnancy can result in serious damage in the developing brain. Bisphenol A (BPA), a plasticizer, is generally known as an endocrine disruptor exhibiting adverse effects when exposed to animals under experimental conditions. The purpose of this study was to investigate the changes in neuronal stem cell proliferation and differentiation during neonatal brain development in BPA-exposed pregnant rats. Methods:After exposure of BPA to pregnant rats, infant brains were excised at days 3, 7, and 14 after birth, and tissues were processed for histological and biochemical analyses. Results:Proliferating cell nuclear antigen (PCNA) immunostaining showed that whereas cells in the hippocampus at days 3 and 7 after birth were highly proliferating, the cells at day 14 divided less often. Immunohistochemical staining for nestin in the control group revealed that nestin-positive cells were only observed at day 3 after birth, but the immunoreactivity was not observed at day 14. In addition, glial fibrillary acidic protein (GFAP) immunoreactive cells were observed from days 7 to 14 in control tissues. However, in the BPA-exposed groups, 1) the number of PCNA- positive cells in the BPA-exposed groups at days 3 and 7 were higher than those of the control, 2) nestin-positive cells were observed at day 3 which is earlier than that of control, and 3) GFAP-positive cells were detected in the hippocampus tissue from day 3. Furthermore, western blotting showed that exposure to BPA in pregnant rats resulted in earlier expression of nestin in the neuronal rat brain compared to the controls. Conclusion:Taken together, it is assumed that precocious neurogenesis in the infant rat hippocampus might be due to BPA exposure during the gestational period. Further studies on adult brain perinatally exposed to BPA are needed to evaluate the pathological status of the hippocampus.
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