Effects Of Exposure To Fenvalerate During Pregnancy On Neurobehavioral Development In Mouse Offspring And Thyroid Signaling Pathway In Fetal Brain

ObjectivesMany previous studies have shown that fenvalerate exposure during development-critical period causes cognitive and behavioral developmental impairment.However,little is known about whether maternal fenvalerate exposure disturbs neurobehavioral development.The purpose of this study was to examine the effects of gestational fenvalerate exposure on neurobehavioral development in the offspring.Meanwhile,we also studied the role of thyroid signaling pathway in fetal brain during the neurobehavioral development.MethodsEstablishment of model that maternal fenvalerate exposure during pregnancy impairs neurobehavioral development in mouse offspring: The ICR mice(8–10 weeks old;32–34 g in male mice;28–30 g in female mice)were purchased from Beijing Vital River whose primary colonies were all introduced from Charles River Laboratories,Inc.There mice were freely allowed to access to food(Beijing Keao Xieli Feed Co,LTD,Beijing 100107)and water at any time.One week prior to use,They were held in a room that was commanded lighting(12 h light/12 h dark cycle),temperature(20–25C)and humidity(50±5%).For mating purposes,four females and two males spend night together starting at 9:00 PM,and females were examined by 7:00 AM the next morning.If a vaginal plug appeared,gestational day(GD)0 was established.In order to control the effect of the quantity and gender of each litter on the experimental results,three male and female offspring were randomly selected in each litter,and the extra littermates were sacrificed.The tests of general physical and neurobehavioral development were performed during lactation period(PND0-PND21).At adulthood(PND30-PND60),the mouse offspring were given a battery of behavior tests which were comprised of morris water maze,open field and elevated plus maze.Morris water maze was used to assess spatial learning and memory abilities,elevated plus maze and open-field tests were used to assess anxiety-related behaviors and spontaneous movement.To investigate the effect of exposure to fenvalerate during pregnancy on thyroid signaling pathway in fetal brain: Pregnant mice were randomly divided into 4 groups.The experimental groups were administered intragastrically with GD0-GD17 at different doses of fenvalerate(0.2,2.0,20 mg / kg),The control mice were orally administered to corn oil daily.Pregnant mice were sacrificed on GD18 day,fetal and maternal sera were taken for thyroid hormone test.In order to study effect of exposure to fenvalerate during pregnancy on thyroid signaling pathway in fetal brain,fetus cerebral cortex was taken for RT-PCR.ResultsIn the Morris water maze test,the results showed that,the escape latency of offspring whose mother exposed to 20.0 mg / kg fenvalerate during pregnancy was longer than that of the control group in positioning navigation experiment,the difference was statistically significant(F=3.15,P<0.05).Further analysis of single sex found that the prolongation of escape latency only appeared in female mouse(F=4.63,P<0.05.Compared with the control group,there was no significant difference between male mouse(F=0.70,P>0.05).In the space exploration experiment,compared with the control group,there was a significant difference in the number of passing through the target quadrant and the target quadrant in group exposed to fenvalerate(20.0 mg / kg)(F=4.62,F=3.36,P<0.05).Further analysis of single sex found that the differences only appeared in female mouse,meanwhile,the differences were statistically significant(F=8.75,F=4.62,P<0.05).In the open-field experiment,compared with the control,the number of feces and rearing in male mouse were increased in group exposed to fenvalerate(20.0 mg / kg),and the difference was statistically significant(F=5.67,F=3.32,P<0.05),whereas no such difference was found in females mouse.In the elevated plus maze experiment,compared with the control group,the frequency on open arms of male mouse in groups exposed to fenvalerate(0.20 mg / kg and 20.0 mg / kg)were decreased,the difference was statistically significant(P < 0.05).In the study that the effect of exposure to fenvalerate during pregnancy on thyroid signaling pathway in fetal brain.There is no impact on the levels of TT3 and TT4 in both maternal and fetal mouse serum.Compared with the control group,The fetal brain cortex D2 and D3 mRNAs were decreased in group exposed to fenvalerate(2.0 mg / kg,20.0 mg / kg)(P <0.05),and the fetal brain cortex OATP1C1 mRNA was decreased in mouse exposed to fenvalerate(P <0.05),however,the MCT8 mRNA was unchanged,the fetal brain cortex TR?1 mRNA was decreased in group exposed to fenvalerate(20.0 mg / kg)(P <0.05),the fetal brain cortex TR?1mRNA was not decreased in group exposed fenvalerate(P> 0.05),the fetal brain cortex BNDF mRNA was significantly decreased in group exposed fenvalerate(20.0 mg / kg)(P <0.05).ConclusionMaternal fenvalerate exposure during pregnancy impairs neurobehavioral development in mouse offspring through a mechanism of interfering thyroid signaling pathway in fetal brain.