邻苯二甲酸二丁酯致尿道下裂大鼠发育异常和阴茎病理学改变研究

目的邻苯二甲酸二丁酯（DBP）孕晚期染毒诱导子代雄鼠尿道下裂发生和探讨DBP致尿道下裂雄鼠发育异常和阴茎病理学改变。方法雌鼠怀孕14～18d，每天分别灌胃给予大豆油（A组），DBP500（B组）、800（C组）、1200（D组）mg／kg体重，分娩后统计仔鼠数和雄仔鼠体重。出生后（PND）7d测量雄仔鼠肛门生殖器距离（AGD），观察尿道下裂发生率和尿道下裂阴茎病理学改变。PND70,对尿道下裂雄仔鼠称重后解剖，评价发育情况。结果C组仔鼠数和雄仔鼠体重明显减少；D组出现孕鼠死亡和零产仔；尿道下裂仅C组发生。发生率为36．5％。PND7，B、C组雄仔鼠AGD和A组相比明显减小。阴茎连续性病理切片显示典型尿道下裂改变。解剖得尿道下裂雄仔鼠肝、肾、前列腺、睾丸、附睾脏器系数与A组相比明显减小，脑垂体脏器系数明显增大。结论800mg／kg体重DBP孕晚期染毒能高诱导雄仔鼠尿道下裂发生，DBP不仅损害雄仔鼠生殖系统，还引起发育异常。

Pathological changes of penis and development abnormalities in hypospadiac male rats by maternal exposure to di-n-butyl phthalate

Objective To induce hypospadiac male rats by maternal exposure to DBP during late pregnancy and investigate pathological changes of their penis as well as development abnormalities. Methods Timed pregnant rats received DBP by gastric intubation at a dose of 0 (group A),500 (group B), 800 (group C) or 1200 (group D) mg/kg from gestation day (GD) 14 to 18. After delivery the number of pubs and body weight of male offsprings were countered. On postnatal day (PND) 7, the incidence of hyposapdias and the anogenital distance (AGD) were evaluated. Transverse serial histologic changes of hypospadiac genitalia were also observed. On PND 70, after anatomy, the developmental conditions of hy-poapdiac male rats were monitored. Results Significant decrease in number of live pubs and body weight of male offsprings was found in group C. Maternal death and complete resorptions of implanted embryos were observed in group D. The occurance of hypospadias was only found in group C and the incidence was 36.5%. Significant decrease in AGD of male rats was observed in groups B and C. The abnormal pathological changes of hypospadiac genitalia were also observed. Anatomical analyses revealed that the organ/ bodyweight ratio of liver, kidney, prostate, testis and epididymis in hypoapdiac rats was significantly decreased as compared with that in control group, whereas the ratio of pituitary gland significantly increased. Conclusion During the critical period of male sexual differentiation, exposure to DBP at dose of 800 mg/kg might lead to a high incidence of hypospadias and not only the male reproductive system but also the developmental condition were damaged by DBP.