| Backgrounds and Objectives 1-nitropyrene(1-NP),a widely distributed contaminant in the environment,is mutagenic and carcinogenic.It is a typical environmental pollutant that can be exposed to 1-NP through the respiratory tract,digestive tract and skin.The developmental toxicity of 1-NP is still unclear,so the study of its developmental toxicity is more meaningful.This study focused on the effects of 1-NP exposure during pregnancy on the growth and development of its offspring and the target of toxic effects,as well as the presence of exposure window and gender differences,and explored the effects on the neurological behavior of offspring during puberty.Method The pregnant ICR mice were randomly divided into 6 groups: early 1-NP exposure group(n=15)and early control group(n=11),medium 1-NP exposure group(n=10)and The intermediate control group(n=10),the late 1-NP exposure group(n=13)and the late control group(n=14).The mice in the early,middle and late exposure groups were given 1-NP(100 μg/kg)early(GD1-GD6),medium(GD7-GD12)and advanced(GD13-GD17)by intragastric administration of 1% of their body weight during pregnancy.In the early,middle and late control groups,the pregnant mice were intragastrically emulsified with GD1-GD6,GD7-GD12 and GD13-GD17,respectively,and the body weight and feed consumption of the pregnant mice were recorded.The pregnant mice were sacrificed on the morning of GD 18 days,and the number of live births,the number of dead fetuses and the number of implants were recorded.For live births,body weight,length,placental weight and placental diameter,as well as gender(identified by ant colony)were measured.The third trimester ICR mice were randomly divided into 4 groups: control group(n=14),1 μg/kg group(n=13),10 μg/kg group(n=12),100 μg./kg group(n=13).Corn oil emulsion and 1 μg/kg,10 μg/kg,100 μg/kg 1-NP emulsion were intragastrically administered at 1% of body weight in the third trimester.On the morning of GD,the pregnant mice were sacrificed,and the placenta material was taken.The pathological sections of the placenta were treated by immunohistochemistry and H&E staining.The sinusoidal area of the placenta and the expression of KI67 in the cell proliferation were analyzed.ICR pregnant rats were randomly divided into two groups: control group(n=17)and 10μg/kg 1-NP treatment group(n=17),and corn was intragastrically administered at 1% of body weight in the third trimester.Oil emulsion and 10 μg/kg 1-NP emulsion.The weight and feed consumption of pregnant mice were recorded daily.Breastfeeding after natural childbirth,the body weight of each female and male pups was weighed by sex.After weaning(3 weeks old),the male and female were separately raised,and the ratio of male to female was adjusted for each litter.Free diet and drinking water,record changes in the weight of the pups.The offspring were divided into 4 groups: female progeny control group(n=16)and female progeny treatment group(n=14),male offspring control group(n=16)and male offspring treatment group(n =16),in the 6th week of the pups(puberty),the open field experiment,the Morris water maze test was carried out at 7 weeks,and the sugar water preference experiment was carried out at 10 weeks to observe the neurobehavioral changes in the offspring.Results The early 1-NP exposure group and the early control group,the mid-stage 1-NP exposure group and the mid-term control group,the late 1-NP exposure group and the late control group had the fetal weights of(1.40±0.03)g and(1.35,respectively).±0.03)g,(1.36±0.04)g and(1.34±0.03)g,(1.39±0.02)g and(1.29±0.02)g,in which the fetal weight of the control group in the late pregnancy group decreased compared with the control group.Significance(P<0.01);body lengths are(23.79±0.26)cm and(23.26±0.21)mm,(23.63±0.23)mm and(23.19±0.30)mm,(23.76±0.19)mm and(22.82±0.21)Mm,in which the length of the third-stage pregnancy group decreased compared with the control group(P<0.01);the placental weight was(0.10±0.01)g and(0.10±0.01)g,(0.11±0.01)g and(0.10±0.01)g,(0.11±0.01)g and(0.10±0.01)g,in which the placenta weight of the control group was significantly lower than that of the control group(P<0.05);the placental diameter was(7.86 ± 0.10)mm and(7.73 ± 0.15)mm,(7.68 ± 0.09)mm and(7.55 ± 0.13)mm,(8.04 ± 0.11)mm and(7.75 ± 0.08)mm,The placenta diameter of the control group in the late pregnancy group was statistically significant(P<0.05).The weight of female and male rats in the third trimester control group and the third trimester treatment group were(1.36±0.02)g and(1.27±0.02)g,(1.40±0.02)g and(1.32±0.02)g,respectively.The body weight of female progeny and male progeny decreased compared with the control group(P<0.01);the length was(23.22±0.26)mm and(22.81±0.11)mm,(23.98±0.21)mm.And(22.81±0.27)mm,in which the male progeny length of the treatment group decreased compared with the control group,which was statistically significant(P<0.01).The late pregnancy control group,1 μg/kg group,10 μg/kg group,the percentage of sinusoidal area in the 100 μg/kg group was 14.83%,14.94%,10.51%,9.81%,respectively,compared with the control group.The sinusoidal area of the 100 μg/kg group was statistically different(P<0.05);the percentage of KI67 positive cells was 13.76%,12.39%,8.41%,and 6.44%,respectively,compared with the control group,10 μg/kg.The group and the 100 μg/kg group were all reduced,which was statistically different.During the first six days of female pups,the latency of the fourth and fifth days of the females in the exposed group was significantly higher than that of the control group(P<0.05);the females in the exposed group were the first.The exercise distances of the four days,the fifth day and the sixth day were also higher than the control group,and there was a statistical difference(P<0.05).In the spatial memory experiment of female rats on the seventh day,the time of staying in the target quadrant of the female rats in the exposed group was lower than that in the control group(P<0.05).Conclusion This study explored the effects of 1-NP exposure during pregnancy on pregnancy outcomes.The results show that 1-NP exposure during pregnancy induces fetal IUGR in a phase-dependent manner.We found that 1-NP exposure in the third trimester caused placental vascular dysfunction in a dose-dependent manner.Exposure to 1-NP in the third trimester also leads to a decline in the spatial learning ability of offspring during puberty.Our results demonstrate for the first time that 1-NP exposure during pregnancy induces fetal IUGR by interfering with placental vascular distribution and proliferation. |
PDF Full Text Request