The Influence And Mechanism Of PCB118 Exposured During Pregnancy On Depression Behaviors In Mice

Polychlorinated biphenyls(PCBs)are a kind of organic pollutants with estrogenic effects that are widespread in the environment.Because of its good physical and chemical stability,it has been widely used in applications.PCBs are lipophilic and bioaccumulative,so they will accumulate in fat tissue for a long time once they enter the organism through various means.And it causes pollution to fat,blood and breast milk.At the same time,the trancmission of PCBs along the placental barrier affects the growth and development of the next genemiceion.PCB118 is one of the 209 kinds of homologues of PCBs.As one of the most lasting PCBs homologue,it has been detected in both ecological environment and animal bodies.As an indicator PCBs,PCB118 can be used as a direct indicator for the assessment of total PCBs in the environment.At the same time,PCB118 can lead to endocrine disorders,reproductive system diseases and abnormal development of nervous system.Previous studies have shown that exposure to PCB118 during pregnancy can lead to behavioral abnormalities in offspring,our previous research has similar results.;Studies have found that human anxiety,depression and other emotions are associated with structural and functional abnormalities in the hippocampus of the brains.While androgen plays a role in regulating emotions by relying on the androgen receptors in the brain.Therefore,we speculate that the effect of PCB118 on emotions may be related to the mechanisms of androgen.In this experiment,female mice and male mice were mated.The female mice that successfully detected were randomly divided into the solvent control group(corn oil),the low dose group with a PCB118 concentration of 20 μg/kg/day,and the high dose group with a PCB118 concentration of 100 μg/kg/day.From the date of seeing the plug,the pregnant mice were given administration imported intragastric until they were produced.Weighing pregnant mice at regular fixed times during pregnancy,recording the gestational time on the day of delivery,the birth weight of newborn mice,the number of litter and male to female ratio;the weight of F1 male mice was weighed at fixed time every week from birth to eight weeks.On the day of harvesting(PND21d,PND35 d,PND56d),the wet weight of the testes of the mice was weighed and the anal colon was measured.At the time of PND21 d,PND35d and PND56 d,mice in each group were randomly selected for tail suspension test and forced swimming test to observe their behavior changes.Then testicular tissues were taken to detect the expression of Ah R,St AR,P450 scc and 3β-HSD at m RNA level.At the same time,the expression of AR in hippocampus was detected by q PCR and western blot.Results: 1)There was no significant difference in weight gain and pregnancy time between the three dose groups in the pregnant mice;2)There was no significant difference in the birth weight,the number of litter and male to female ratio of the F1 mice did not exist between the three dose groups.3)There was no significant difference between the high-dose group of the F1 male mice and the vehicle control group.The weight of the male mice in the low-dose group was not significantly different from that in the solvent control group on the day of PND0 d,PND7d,PND14 d.But there are significant differences and changes in body weight at PND21 d,PND28d,PND35 d,PND42d,PND49 d and PND56 d.4)The wet weight of testes of F1 generation male mice was measured on the same day,and anal colonization was measured.Compared with the solvent control group,there was no significant difference in the high-dose group at different time points.The wet weight of testes in the low dose group was significantly lower than that in the PND21 d,PND56d,the PND35 d and the anal distance in the PND21 d,PND35d,and the wet weight of the testes in the low dose group was significantly lower than the control group.There was a significant decrease in PND56 d.5)Low-dose F1 male mice showed an immobility time increase in the tail suspension experiment.There was no difference between the high-dose male mice and the solvent control group.In addition to the high dose group in the experiment at PND35,and there was no significant difference in other time periods.6)The testosterone level in the serum of F1 male mice was affected by PCB118;7)The m RNA expression level of Ah R,St AR and P450 scc in the testis of F1 male mice changed,but PCB118 did not affect the expression of 3β-HSD on m RNA;8)The expression of AR in the hippocampus of F1 male mice in the low dose group showed a significant decrease in each time period.In conclusion,the results showed that female mice exposed to low dose of PCB118 during pregnancy could change the behavior of F1 generation male mice,inhibit depression-like behavior,and decrease the testosterone level in serum at the same time.Testosterone synthesis-related enzymes in testis and AR expression in hippocampus were changed.We hypothesized that low-dose PCB118 can affect the expression of testosterone synthesis-related enzymes through the Ah R pathway,it also affect the expression of AR in the hippocampus and the action of testosterone,and ultimately lead to depression-like behavior in mice.