title: Perinatal exposure to bisphenol-A inhibits synaptogenesis and affects the synaptic morphological development in offspring male mice.
abstract: Our previous study indicated that perinatal exposure to low-dose BPA, one of the most common environmental endocrine disrupters, alters behavioral development in offspring mice. Given that synaptic structure of the hippocampus is closely related to behaviors, in the present study, we examined the effects of perinatal exposure to BPA (0.04, 0.4, and 4.0 mg kg(-1) day(-1)) on the synaptic density and the synaptic structural modification of pyramidal cells in hippocampus region CA1 and the expressions of synaptic proteins such as synapsin I and PSD-95 and glutamate NMDA and AMPA receptors in male offspring mice on postnatal day (PND) 14, 21, and 56. The results of electron microscope measurement showed that BPA significantly reduced the numeric synaptic density and altered the structural modification of synaptic interface of pyramidal cells with the enlarged synaptic cleft, the shortened active zone, and the thinned postsynaptic density (PSD) on PND 14, 21, and 56 and the increased curvature of synaptic interface on PND 14 and 21. Further analyses of Western blot indicated that BPA markedly reduced the levels of synapsin I and PSD-95 on PND 14, 21, and 56 and down-regulated NMDA receptor subunit NR1 and AMPA receptor subunit GluR1 during development and young adulthood. These results suggest that perinatal exposure to low level of BPA inhibits synaptogenesis and affects synaptic structural modification after birth. The reduced expressions of synaptic proteins synapsin I and PSD-95 and glutamate NMDA and AMPA receptors may be involved in the negative changes in the synaptic plasticity.
authors.affiliation: Chemistry and Life Science College, Zhejiang Normal University, Jinhua 321004, China. xuxh63@zjnu.cn
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Xu
authors.forename: Lingdan
authors.initials: L
authors.lastname: Xie
authors.forename: Xing
authors.initials: X
authors.lastname: Hong
authors.forename: Qin
authors.initials: Q
authors.lastname: Ruan
authors.forename: Hongfei
authors.initials: H
authors.lastname: Lu
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhang
authors.forename: Guangxia
authors.initials: G
authors.lastname: Zhang
authors.forename: Xingyi
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism; D001559:Benzhydryl Compounds / Q000633:toxicity*; D052244:Endocrine Disruptors / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D008297:Male; D051379:Mice; D055495:Neurogenesis / Q000187:drug effects*; D010636:Phenols / Q000633:toxicity*; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism; D016704:Synapsins / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D010636:Phenols; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D016704:Synapsins; C409466:NR1 NMDA receptor; C006780:bisphenol A; D000098826:Bisphenol A Compounds