| ObjectivesFenvalerate(FEN),as a typical pyrethroid insecticide,is widely used in daily life and planting.Previous studies have shown that maternal fenvalerate exposure during pregnancy induces anxiety-like behavior in offspring,but whether paternal exposure induces anxiety-like behavior in offspring remains unclear.In this study,an animal model of paternal fenvalerate exposure was established to analyze the effects of paternal fenvalerate exposure on anxiey-like behavior of offspring mice,and to explore the damage effect of paternal fenvalerate exposure on prefrontal cortex synapses of offspring mice.Through this study,the effects of paternal pyrethroid exposure on the emotional and behavioral development of offspring were further studied,and the effects on prefrontal synaptic damage of progeny were preliminarily discussed,providing a theoretical basis for the subsequent exploration of the molecular mechanism of paternal fenvalerate exposure.MethodsAnimal models of paternal fenvalerate exposure were established.Clean grade ICR mice were purchased from Beijing Vitong Lihua Co.,LTD.(Certificate batch No.:SCXK(Beijing)2015-0001),including 45 7-week-old male mice(30-35g)and 457-week-old female mice(26-30g).After one week of adaptive feeding in a standard hygienic mouse house before the formal experiment,male mice were randomly divided into three groups(15 in each group),namely,fenvalerate high-dose group,fenvalerate low-dose group and control group.The male rats in the poisoned group were given the drug by oral intragastric administration every day for five weeks.After poisoning,male rats and untreated female rats were combined in a ratio of 1:1.Offspring mice were normally fed until adulthood.On day 61 of PND61,open field and elevated cross maze behavior experiments were conducted to observe the anxiety-like behavior of offspring mice.Histological samples(whole brain and prefrontal lobe)were taken from the offspring that did not undergo behavioral experiments.In this study,pathological changes of prefrontal cortex of progeny mice were observed by HE staining,Nissl staining and Golgi staining,and the effects of paternal fenvalerate exposure on prefrontal synapses of progeny were investigated by molecular biological experiments such as protein immunoblotting and RT-PCR.ResultsDuring fenvalerthrin administration,there were no significant differences in food intake and body weight of paternal male mice,and there was no difference in body weight of offspring mice from birth to adulthood.In open field experiment,the central activity time of male offspring in fenvalerthrin treated group was significantly lower than that in the control group(P < 0.01),but there was no significant difference in the central activity time of female offspring compared with the control group(P > 0.05).Secondly,the standing times of male offspring mice in fenvalerthrin treatment group were significantly higher than those in control group(P < 0.01),while the standing times of female offspring mice in fenvalerthrin treatment group had no significant difference compared with control group(P > 0.05).In the elevated cross maze experiment,the arm opening time of male offspring mice in fenvalerthrin treatment group was significantly lower than that in control group(P < 0.05),and the arm opening times of male offspring mice in fenvalerthrin treatment group was significantly lower than that in control group(P < 0.05).Compared with the control group,there were no significant differences in the open arm time and open arm times of female progeny(P > 0.05).HE staining results showed that the number of normal neuron cells in the control group was more,and the cytoplasmic staining was uniform and orderly,while the number of normal neuron cells in the fenvalerate treatment group was reduced.The results of Nissl staining showed that the shape of neuron cells in the control group was complete,the cytoplasmic blue staining was uniform,the cells were arranged neatly and tightly,and there were fewer nucleolystic neurons.In the fenvalerthrin treatment group,the number of neuron cells in the prefrontal cortex was reduced,with irregular shape and irregular arrangement.The number of progeny prefrontal nucleus neurons increased significantly in fenvalerate treatment group(P <0.01).Golgi staining results showed that,compared with the control group,the distribution of neuronal dendritic spines was sparse in the fenvalerate high-dose and low-dose groups,and the number of mature dendritic spines was less.Quantitative analysis using Image J software showed that the density of dendritic spines of male prefrontal cortex neurons in the fenvalerate treatment group was significantly lower than that in the control group(P < 0.01).The results of western blotting showed that the level of PSD95 protein in prefrontal cortex of male offspring in fenvalerate high-dose group was significantly lower than that in control group(P < 0.05).The Gephyrin protein level in prefrontal cortex of male offspring in fenvalerate low dose group was significantly lower than that in control group(P < 0.05);There were no significant differences in the expressions of PSD95 and Gephyrin proteins in the prefrontal cortex of female progeny compared with the control group(P > 0.05).The protein level of male progenitor’s prefrontal cortex BDNF(Brain-derived neurotrophic factor)in fenvalerate low dose and high dose groups was significantly lower than that in unexposed group(P < 0.05);There was no significant difference in the expression of BDNF protein in the prefrontal lobe of female offspring mice.The results of RT-PCR showed that BDNF m RNA level in the prefrontal cortex of male offspring in fenvalerthrin high-dose group was significantly decreased(P < 0.05),but there was no significant difference in the level of BDNF m RNA in the prefrontal cortex of female offspring(P > 0.05).ConclusionsPaternal fenvalerate exposure induces anxiety-like behavior in offspring mice in a sex-dependent manner(mainly affecting male offspring),and prefrontal synaptic damage may play a key role in offspring mice. |
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