【作者】 李岩；

【导师】 吴德生；

【作者基本信息】 四川大学 ， 劳动卫生与环境卫生学， 2006， 博士

【摘要】 尿道下裂是小儿泌尿外科常见畸形之一，主要见于男性。据国外统计，活产婴儿中发病率近1／250-1／300，我国发病率约为2-3／1000。近三十年来，此病发病率有明显增加的趋势，几乎增加了一倍，这显然是用遗传因素所不能解释的，当然不能排除监测或报告系统逐渐完善外，但病例的增加之迅速应当另有原因。 目前，很多泌尿生殖的领域的学者已把注意力放在外界环境中，一些学者认为环境中广泛存在的环境内分泌干扰污染物可能是造成尿道下裂发病率上升的原因。但环境污染物作用于人，引发尿道下裂的发病的生物效应机制并不十分清楚，有研究者推测，环境污染物可能是通过迫使机体正常内分泌因素改变而发生下裂畸形，因为人们经常摄入或接触有抗雄激素的活性的外源性物质如杀虫剂、塑料制品的副产品、药物等等，导致其出生的后代出现尿道下裂发生。从某种程度上看，环境内分泌干扰物更可能解释全球范围内尿道下裂发生和发病率升高的某些原因。 已有的研究表明，环境中具有抗雄激素活性的物质能与雄激素受体(androgen receptor；AR)相互作用，与雄激素竞争AR，主要是AR拮抗剂，被称为环境抗雄激素。众所周知，雄激素在雄性显型表达中起着关键的作用，以及AR在性分化和发育过程介导雄激素作用的重要性，环境抗雄激素暴露更有可能对雄性生殖系统发育产生不良影响，因此环境抗雄激素的研究受到了广泛的关注。自上世纪九十年代以来，有关环境抗雄激素物质干扰健康效应的报导逐渐增多，研究资料显示，抗雄激素物质能够引起鱼类及多种野生生物的生殖功能下降，动物实验研究结果表明，抗雄激素物质能改变体内的性激素平衡，损伤雄性动物的生殖功能，但有关抗雄激素物质对生殖发育毒更多还原

【Abstract】 Hypospadias is one of common diseas in pedo-urinary surgery from main male. According to overseas statistics,its incidence is 1 / 250-1 / 300 in liveborn infant and 2-3 / 1000 in China. In the past 30 years,its incidence have increased almost one time.This do not explain apparently by inherit.Of course,we do not exclude the cause of the system of monitoring and reporting, we think that the reason of the rapid increasing case should be considered.Now,many scholar put the attention on environment in genito-urinary domain.They consider that the widespread pollutant may produce the increasing reason of hypospasias in environment.But,the elevated mechanism of biological effect is not clear yet in the world.Many suppose that environmental polluant may alter the factor of endocrine in animals to result in hypospasias.It is proved that people usually ingest and contact antiandrogenic substance,such as insecticide,by-product of plastics,medicine etc.In a way environmental polluant can explain the elevated reason of hypospadias in the world.Recently,some investigation manifest antiandrogenic substance can compete AR with androgen,many of them are the antagon of AR.These substance are called the environmental antiandrogen.It is known to all that androgen puts a key role in the expression male phaenotype and AR puts a impotantance in the effect of mediating androgen in sex differentiation and sex development.The exposure of environmental antiandrogen may produce harmful effects all the more on male reproductive systerm.Therefor,people pay close attention to it.Many studies have shown that antiandrogen can impair the reproductive functions of male animals through breaking the internal sex hormone更多还原