Effects Of Arsenic Exposure In Male Mice On Offspring Intrauterine Development And After Adulthood Neurobehavioral Development

Objective To study the damaging effects of drinking water arsenic exposure during spermatogenesis of adult male mice on fetal mice intrauterine development and explore its related mechanisms;to study the effects of drinking water arsenic exposure during spermatogenesis of adult male mice on neural behavior development of offspring.Methods This study consists of two parts.In the first part,the effects of arsenic drinking water exposure on spermatogenesis of adult male mice on the intrauterine development of fetal rats were investigated,and their related mechanisms were explored.At 8 weeks,male ICR mice were randomly divided into a control group and an arsenic(As)exposed group.The control group drank three distilled water,and the arsenic exposed group drank arsenic water containing sodium arsenite(15 mg / L).After 35 days of drinking water treatment,male mice in the control group and the arsenic group were mated with male and female ICR female mice at a ratio of 1: 1,and the female mice were examined for vaginal plugs the next morning.Day0 of pregnancy(GD0).Mating was continued for 5 days,and the number of successful matings and the number of successful pregnant mice were recorded.GD18 was used to sacrifice a part of pregnant mice,evaluate the fetal mice’s intrauterine development,and save the placenta for histopathological examination and expression of development-related genes in the placenta.Another batch of 8-week male ICR mice was purchased and randomly divided into the control group and the arsenic group as described above.After drinking water for 35 days,they were mated to ICR female mice.GD10 pregnant rats were sacrificed and the placenta was used to detect epithelial-mesenchymal transition.mesenchymal transition(EMT)-related protein expression.In the second part,the effects of arsenic drinking water exposure on spermatogenesis of adult male mice on the neurobehavioral development of offspring were studied.The first part of 10000 the experiment,GD18,did not sacrifice pregnant rats to give birth naturally.On the fourth day after birth,4 male and female pups in the litter were adjusted,and behavior-related experiments(open field,water maze)were carried out in adulthood.Another part of the F1 generation mice was grown,the control group(Control,C),arsenic group(Arsenic,A),the different groups were mated in four ways to conceive and give birth to F2 generation,F2 generation adult behavioral experiments(Open field,water maze).Result Adult male mice were exposed to arsenic after drinking water for 35 consecutive days,which did not affect the drinking and diet of the mice,but the mice gained weight.The mating rate of arsenic-exposed male mice and the fertility rate of female mice after successful mating were not different from those of the control group.After exposure,pregnant women who had conceived after mating had significantly more abortions and stillbirths than the control group;fetal mice in the arsenic group were lighter than the control group,and the length of the top buttocks was smaller than the control group,resulting in growth restriction;There was no difference in the group,the placenta weight was heavier than that in the control group;the pathological morphology of the placenta was detected,and the placental morphology of the arsenic group was significantly changed.Increased proportion;glycogen staining found that placental glycogen cells in the arsenic group increased in the trophoblast,control glycogen cells were concentrated in the decidua and trophoblast near the decidua,while arsenic group glycogen cells penetrated the entire placenta;arsenic The expression of E-cadherin protein increased,the expression of Vimentin protein decreased,and the EMT process was inhibited in the group.The cluster analysis of sperm DNA methylation level showed that the arsenic group and the control group were clearly divided.Class,arsenic exposure changes its male sperm DNA methylation,while the progeny developed fetal placenta closed first nine imprinted gene expression was also affected.Male arsenic exposure did not significantly affect the anxiety and exploration ability of FI mice,and did not affect the learning ability of F1 and F2 generations,but significantly damaged the males of F1 and F2 A(♂)XC(♀)groups.Mice memory.Conclusion Adult male mice exposed to sodium arsenite in the spermatogenic cycle of drinking water,which inhibited the migration of glycogen cells to decidua by inhibiting the EMT process including glycogen cells and affected the normal development of placenta.Causes abortion,death and growth restriction in fetal mice.Impaired placental development may be that arsenic alters sperm DNA methylation in male mice,which in turn affects the expression of related imprinted genes that play an important role in placental development.Male arsenic exposure impaired the memory ability of the male and female offspring A(♂)XC(♀).