妊娠中末期邻苯二甲酸(2-乙基己基)酯暴露对母鼠妊娠结局及子鼠生长发育的影响

Effects of maternal exposure to Di(2-ethylhexyl) phthalate during mid-to late pregnancy on pregnancy outcome and offspring development

目的观察妊娠中末期邻苯二甲酸(2-乙基己基)酯(DEHP)经口染毒对母鼠妊娠结局及子鼠生长发育的影响。方法 50只Wistar雌鼠妊娠12 d时随机分入4个染毒组(DEHP浓度分别为1、250、750、1 000 mg/kg,n=10)和1个对照组(n=10);染毒组DEHP灌胃染毒至妊娠17 d,对照组仅给予玉米油。观察DEHP对母鼠行为、体质量、妊娠结局、脏器系数的影响,以及DEHP对子鼠体质量和雌性子鼠阴道开口的影响。结果染毒期间,各DEHP染毒组母鼠体质量增加,各染毒组每窝活胎数量与对照组比较,差异均无统计学意义(P>0.05);未观察到死胎、畸胎。子鼠出生第22天,各染毒组母鼠子宫、卵巢、肝脏、脾脏、肾脏、胸腺、下丘脑、脑、肾上腺的脏器系数与对照组比较,差异均无统计学意义(P>0.05)。各染毒组子鼠出生后1～22 d体质量增加值与对照组比较,差异均无统计学意义(P>0.05)。出生后66 d,750 mg/kg及1 000 mg/kg DEHP染毒组雌性子鼠出现阴道闭锁畸形,分别占62.50%和81.25%,其余各组雌性子鼠阴道全部正常开口。结论 750、1 000 mg/kg DEHP妊娠中末期经口染毒未导致大鼠母体、胚胎一般毒性,可观察到雌性子代成年后阴道闭锁现象。

Objective To investigate the effects of maternal exposure to Di(2-ethylhexyl) phthalate(DEHP) during mid-to late pregnancy on pregnancy outcome and offspring development. Methods Fifty pregnant Wistar rats were randomly assigned to 1 mg/kg DEHP treatment group,250 mg/kg DEHP treatment group,750 mg/kg DEHP treatment group,1 000 mg/kg DEHP treatment group and control group(n=10) on pregnancy day 12.Treatment groups were managed with 1 mg/kg,250 mg/kg,750 mg/kg and 1 000 mg/kg DEHP through day 17,respectively,and control group were administered with corn oil.The effects of DEHP on behavior,body weight,pregnancy outcome and organ coefficient of pregnant rats,and the effects of DEHP on body weight of offsprings and on vaginal orifice of female offsprings were observed. Results The weight gain of rats in DEHP treatment groups were not affected during exposure period(P>0.05).There was no significant difference in average viable litter size between each treatment group and control group(P>0.05),and no fetal malformation and stillbirth was observed.Twenty-two days after delivery,there was no significant difference in organ coefficient of uterus,ovary,liver,spleen,kidney,thymus,hypothalamus,brain and adrenal gland between treatment groups and control group(P>0.05).There was no significant difference in weight gain of offsprings from day 1 to day 22 after birth between each treatment group and control group(P>0.05).Sixty-six days after birth,62.5% of female offsprings of 750 mg/kg DEHP treatment group and 81.25% of female offsprings of 1 000 mg/kg DEHP treatment group developed vaginal atresia,while no such abnormality occurred in the other groups. Conclusion Maternal exposure to 750 mg/kg and 1000 mg/kg DEHP during mid-to late pregnancy may not cause significant maternal toxicity,while high incidence of vaginal atresia in adult offsprings can be observed.