Effects Of Maternal Exposure To Di-(2-ethylhexyl) Phthalate During Pregnancy And Lactation On Hippocampal Synapsis In Offspring

Objective:The study were to explore whether maternal exposure to di-2-ethylhexyl phthalate(DEHP)during pregnancy and lactation affected the development of hippocampal synapsis in offspring,to analyze the effects of DEHP exposure on synaptic plasticity,synaptic morphology and structural changes,and the expression of synaptic proteins in offspring hippocampus.Methods:Female Wistar pregnant rats were randomly divided into Control group,30,300 and 750 mg/kg/day dose group,each group was intragastrically administered with a corresponding concentration of DEHP corn oil solution.In PN80 of the pups,long-term potentiation(LTP)in hippocampus region CA1 were detected by electrophysio logical method.In PN7,PN14 and PN21 of the pups,the ultrastructure of synapses in the hippocampus region CAl was observed by electron microscopy including the width of synaptic cleft and the thickness of postsynaptic density.Immunofluorescence was used to observe the positive expression of hippocampal synaptophysin(SYN)and postsynaptic density protein 95(PSD-95)in each group,and Western Blot method was used to further detect the expression levels of SYN and PSD-95.Results:(1)The results of electrophysiological experiments showed that after the induction of LTP by high-frequency stimulation,compared with the control group,the success rate of LTP induction was significantly reduced in the 3 OOmg/kg/day and 750mg/kg/day dose groups,and the relative values of PS amplitude and EPSP slope were significantly reduced(P<0.05),For female pups,the relative values of PS amplitude and EPSP slope showed no significant difference in each group(P>0.05).(2)Electron microscopy showed that compared with the control group,the width of the synaptic cleft was significantly increased(P<0.05)and the thickness of postsynaptic density was significantly decreased(P<0.05)in male offspring in the 300mg/kg/day and 750mg/kg/day dose groups.While these synaptic structural parameters of female offspring in each group were not significantly changed(P>0.05).(3)The results of immunofluorescence and Western Blot showed that in PN7,PN14 and PN21 of the pups,compared to control group,the expression levels of SYN and PSD-95 in hippocampal tissues of male offspring at 300mg/kg/day and 750mg/kg/day were significantly decreased(P<0.05),while the expression levels of synaptic related proteins in hippocampal tissues of female offspring in each group were not significantly different(P>0.05).Conclusions:(1)Maternal exposure to DEHP during pregnancy and lactation inhibited the induction of LTP in the hippocampus region CA1 of male rats and affected synaptic plasticity.(2)Maternal exposure to DEHP during pregnancy and lactation inhibited the development of synaptic morphological structure in hippocampus region CA1 of male rats and affected the plasticity of synaptic structure.(3)Maternal exposure to DEHP during pregnancy and lactation reduced the expression levels of synapse related proteins SYN and PSD-95 in hippocampal region CA1 of male rats.