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目的研究妊娠期甲醛和苯联合染毒对小鼠胚胎发育的影响。方法将妊娠0天的昆明小鼠随机分为对照组、低剂量组、中剂量组、高剂量组,并分别于妊娠第6天开始进行吸入式染毒,连续15 d,甲醛和苯的剂量为国家室内空气标准的0倍、1倍、50倍和100倍。仔鼠出生后,记录正常生产孕鼠数、产仔数、流产孕鼠数及出生24 h后存活的仔鼠数。仔鼠称重后分离肝及脑组织并进行RT-PCR,检测部分脑、肝发育相关基因在组织内的表达情况。取仔鼠肝组织,固定后免疫组化检测IGF-1的表达情况。结果高剂量组的流产孕鼠数高于对照组、低剂量组及中剂量组(P<0.05);高剂量组的产仔数、存活数低于其余各组(P<0.05);中剂量组、高剂量组仔鼠体重低于对照组和低剂量组(P<0.05);高剂量组发育相关基因Peg3和IGF-1的表达强度低于对照组、低剂量组及中剂量组(P<0.05)。免疫组化结果显示仔鼠肝组织中IGF-1表达降低。结论妊娠期接触甲醛与苯混合气体可导致孕鼠流产率上升、产仔数、仔鼠存活数、仔鼠体重下降,同时也会导致胚胎发育过程中重要基因IGF-1和Peg3表达下调。
Objective To study the effects of combination of formaldehyde and benzene during pregnancy on embryonic development in mice. Methods Kunming mice at 0 days of gestation were randomly divided into control group, low dose group, middle dose group and high dose group. The mice were inoculated by inhalation on the 6th day of gestation. The doses of formaldehyde and benzene 0 times, 1 times, 50 times and 100 times as the national indoor air standard. After the pups were born, the number of normal pregnant rats, litter size, the number of pregnant rats born aborted and the number of pups alive after 24 hours of birth were recorded. The pups were weighed and then isolated from the liver and brain tissues for RT-PCR to detect the expression of some brain and liver development related genes in the tissues. The offspring liver tissues were harvested and fixed for immunohistochemistry to detect the expression of IGF-1. Results The numbers of aborted pregnant rats in high dose group were higher than those in control group, low dose group and middle dose group (P <0.05). The number of litter size and survival in high dose group were lower than those in other groups (P <0.05) (P <0.05). The expression of Peg3 and IGF-1 in the high-dose group was lower than that in the control group, the low-dose group and the middle-dose group <0.05). Immunohistochemistry results showed that the IGF-1 expression in the offspring liver tissue decreased. Conclusions Exposure to formaldehyde and benzene during pregnancy may lead to the increase of abortion rate, litter size, offspring surviving number and offspring weight in offspring mice, and may also lead to the down-regulation of IGF-1 and Peg3 expression during embryogenesis.