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目的采用塑化剂邻苯二甲酸二(2-乙基)己酯(DEHP)宫内暴露诱导建立大鼠尿道下裂模型,观察DEHP的外生殖器毒性作用。方法孕鼠40只,完全随机分成4组:正常对照组和DEHP低中高3个剂量组[分别为500、750、1 000 mg/(kg.d)]。在怀孕天数(GD)第12～19天连续灌胃,出生后(PND)第1天即对新生鼠进行计数,称体质量和测量肛门至生殖器之间的距离(AGD);PND30测量阴茎长度,观察每组雄性仔鼠的尿道开口位置,判断有无尿道下裂及其严重程度并切取整个阴茎进行病理组织HE染色。结果与对照组相比,随着DEHP暴露剂量增大,每窝产活仔数及雄性活仔数均较对照组有显著减少;同时仔鼠的体质量减轻、AGD和阴茎长度缩短明显(P<0.05,P<0.01)。DEHP低、中、高剂量组诱导出雄性仔鼠尿道下裂发生率分别为10.7%、30.6%和37.0%,与正常对照组比较,差异显著(P<0.05,P<0.01);重型尿道下裂发生率分别为0、8.3%和22.2%;阴茎组织横截面石蜡切片HE染色予以验证。结论 DEHP大鼠宫内暴露成功建立尿道下裂模型,且对子代具有一定的发育和外生殖器毒性效应。
OBJECTIVE: To establish the model of hypospadias induced by intrauterine exposure of plasticizer di-2-ethyl hexyl phthalate (DEHP) and to observe the genital toxicity of DEHP. Methods Forty pregnant rats were randomly divided into 4 groups: normal control group and DEHP low, medium and high dose groups [500, 750 and 1 000 mg / (kg · d), respectively]. The newborn mice were counted on the first day after birth (PND), and the body mass was measured and the distance from the anus to the genitals (AGD) was measured. The penis length was measured by PND30 The position of urethral opening in each group of male offspring was observed to determine the presence or absence of hypospadias and its severity and the entire penis was cut for HE staining. Results Compared with the control group, the number of live births per litter and the number of live pups in the litter significantly decreased as the dose of DEHP increased. At the same time, the weight of the offspring was reduced, and AGD and penile length shortened significantly (P <0.05, P <0.01). The rates of hypospadias induced by DEHP in low, medium and high dose groups were 10.7%, 30.6% and 37.0%, respectively, which were significantly different from those in normal control group (P <0.05, P <0.01) The incidence of cleft was 0, 8.3% and 22.2%, respectively. Paraffin sections of penile tissue sections were verified by HE staining. Conclusion The model of hypospadias was successfully established in intrauterine exposure of DEHP rats and had some developmental and genital toxicity effects on offspring.