| Objective: To establish a rat model of human cytomegalovirus(HCMV)infection in early pregnancy,and to investigate the symptoms of autism spectrum disorder(ASD)in the model offspring.Methods: Fourteen pregnant SD rats were randomly divided into control group and experimental group with 7 rats in each group.The experimental group(HCMV group)was intraperitoneally injected with 0.5 m L of 1×10^6TCID50 HCMV virus suspension,while the control group(HELF group)was intraperitoneally injected with 0.5 m L of the same amount of human embryonic lung fibroblast(HELF)supernatant.The reaction of the two groups after inoculation was observed.Meanwhile,6 offspring mice were randomly selected from HCMV group and HELF group,respectively.Evaluate the histopathology in the two groups of young rats(HE staining,electron microscopy)and autistic neuroethology test(including the Morris water maze,stereotyped behavior,open field,suspension,slope and inclined plate experiment),compared two groups of young rats in autism symptoms and neurobehavioral development differences,and statistical analysis,measurement data comparison between the two groups using t test,P< 0.05,with statistical significance.Results:(1)The results of HE staining and pathological examination of electron microscopy showed that the damage of hippocampal myelin sheath was more obvious in the offspring of the experimental group than in the control group.(2)Morris swimming distance: HCMV group 1-4 days total distance(d1:17.97±3.82;d2:15.22 ±2.96;d3:14.22±2.08;d4:10.87±2.34)m,which was higher than that of the HELF group in 1-4 days(d1:9.36±1.95;d2:6.31±1.65;d3:5.36 ±1.23;d4:5.01±1.24)m,the difference was significant(P<0.01).The results indicated that there were differences in motor ability between the two groups,and the motor ability of HCMV group was significantly lower than that of HELF group.(3)Styled behavior results: The number of styled actions in HCMV group(40.7±3.98,38.7±3.4,38.3±4.13,40.2±3.4,39.7±2.01,38.5±3.00)was significantly higher than that in HELF group(18.5±2.70,21.7±3.17,26.4±3.26,20.2±2.29,19.2±2.94,20.9±3.00),with significant difference(P<0.01).The results indicated that there were differences in the detection of stereotyped behaviors between the two groups,and the stereotyped behaviors in HCMV group were significantly more than that in HELF group.(4)The results of open field experiment: the standing times of HCMV group(19.15±3.63)and the number of cells across(41.70±11.05)were significantly lower than those of HELF group(22.05±4.14)and the number of cells across(66.05±12.57)(P<0.05).These results indicated that there were differences between the two groups in the open field test.Compared with the HELF group,the exploratory behavior,tension and autonomous behavior of the newborn mice in the new environment were significantly reduced in the HCMV group.(5)The scores of offspring in HCMV group were significantly lower than those in HELF group in suspension test,slope test and inclined plate test.The results indicated that there was a difference in the development of motor ability between the two groups,and the motor ability of HCMV group lagged behind that of HELF group.Conclusions: HCMV infection in early pregnancy induced autism spectrum symptoms in offspring of SD rats,suggesting that HCMV infection in utero during early pregnancy may be one of the causes of autism spectrum disorders. |
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