Effect Of Hypoxia During Pregnancy On Autism-like Behavior In Offspring Rats

Objectives: To figure out the effects of different degrees of hypoxia during pregnancy on the nervous system of offspring and the relationship between hypoxia and autism-like behavior of offspring,and to explore whether HIF-1α plays a role in the pathological process.Methods: Pregnant rats were divided into control group,VPA group and prenatal hypoxia group randomly.The prenatal hypoxia group was further divided into PH 1 group,PH 2 group,PH 3 group,and PH 4 group.The group of PH 1 was hypoxic for 3 hours on the 13 th day of pregnancy(E13d),the group of PH 2 was hypoxic for 6 hours on E13 d,the group of PH 3 was hypoxic for 3 hours on E17 d,and the group of PH 4 was hypoxic for 6 hours on E17 d.After hypoxia,the pregnant rats were fed normally until delivery.Three chamber test and open field test were used to conduct behavioral analysis of the offspring,we use Morris water maze test was conducted to evaluate the offspring rats’ learning and memory ability.Quantitative real-time reverse transcription PCR(q RT-PCR)was used to detect the m RNA expression of TNF-α in the hippocampus.The expression of HIF-1α,PTEN,Glu R2,NR2 A and other proteins in the hippocampus were detected by western blotting.Results: Open field test results indicate that the grooming time of VPA,PH 3 group and PH 4 groups in open field increased significantly compared with control group.In the three-chamber test,the VPA group,PH 3 group and PH 4 spent more time in the object zone than the control group but less in the rat area,while PH 1 group and PH 2 group are no different from control group statistically.Then we analyzed the results by sex and found that there is no gender difference in the stereotype behaviors.In Morris water maze test,there was no difference in the distance that the rats in each group traveled on the first day.In the water maze navigation training days,the incubation period of the rats in finding the platform was shortened with the increase of training days.In the final day,except for the control group,the times of crossing the area where the original island was located decreased in all groups when the platform was removed.Besides,the reduction of VPA group,PH 3 group and PH 4group were statistically different from that of the control group.PCR results showed that TNF-α was significantly increased in VPA group and PH 4 group,Western blot results showed that HIF-1α expression was up-regulated in PH 4 group and PTEN expression was down-regulated in PH 4 group,and the expressions of synaptic related proteins Gl UR2 and NR2 A were increased in PH 4 group compared with control group,while there are no difference of other groups compared to control group.Conclusions: Late hypoxia in pregnant rats is more likely to induce autism-like behavior in offspring and HIF-1α plays a role in the mechanism,which may be accomplished by synaptic associated proteins.