Influence of endocrine disrupting chemicals on the health of future generation

[孕妇队列研究](1)受试者为孕周在26周至35周之间的孕妇，340名受试者被招募至2004年2月。(2)对孕妇进行问卷调查，内容包括饮食、家庭环境等。(3)对婴儿进行神经行为测试：6个月和18个月时采用贝利婴儿发育量表，7个月时采用Fagan婴儿智力测验。(4)测定孕妇及新生儿FT4、TSH水平。(5)检测脐血IgE水平。(6)检测了100名孕妇的二恶英和多氯联苯水平。检测了15对母血和脐带血的全氟辛烷磺酸水平。全氟辛烷磺酸在人体内的蓄积是可以测量的，母血和脐带血中全氟辛烷磺酸浓度之间存在高度的相关性。(7)外源TIN代谢酶基因多态性的研究。(8)观察胎盘中P450的表达及内分泌干扰物的暴露情况。(9)将对这些婴儿进行数年的随访，调查内分泌干扰物对他们神经行为发育和过敏性疾病的影响。[尿道下裂和隐睾症的病例对照研究]在大学医院、札幌市的相关医院和北海道以外的其他医院进行了尿道下裂和隐睾症的病例对照研究。(1)为了研究尿道下裂与类固醇代谢酶基因多态性之间的关系，携带Hsd17b3基因S等位基因(G289S)的男孩患上尿道下裂的风险增加，尤其是远端类型。携带SRD5A2基因V等位基因(L89V)的男孩患尿道下裂的风险降低，但差异不显著。(2)在CYP1A1基因3‘侧翼区MSPL杂合子母亲中，发生尿道下裂的优势比显著降低，与先天性畸形母亲的趋势相似，但差异无统计学意义。

[Cohort study from pregnant women](1) Subjects were pregnant women between gestation weeks 26 and 35, and 340 was recruited until Feb. 2004. (2)Diet, home environment, etc. were included in a questionnaire to pregnant women. (3) Their infants were assessed by neurobehavioral tests : the Bayley Scales of Infant Development at 6 and 18 months old, and the Fagan Test of Infant Intelligence at 7 months old. (4) Levels of FT4 and TSH of pregnant women and newborns were measured. (5) A level of IgE of cord blood was measured. (6) Levels of dioxin and PCBs of 100 pregnant women were measured. Levels of PFOS of fifteen pairs of maternal and cord blood samples were measured. PFOS accumulation could be measured in human and there was a high correlation between PFOS concentrations in maternal and cord blood. (7) Gene polymorphisms of xenobioticTinetabolizing enzymes were investigated. (8) Expression of P450 and exposure of endocrine disrupting chemicals in the placentas were investigated. (9) These infants will be followed up for several years, and influence of endocrine disrupting chemicals on their neurobehavioral development and allergic diseases will be investigated.[Case-control studies of hypospadias and cryptorchidism]Case-control studies of hypospadias and cryptorchidism were performed in the university hospital, its related hospitals in the city of Sapporo, and other hospitals outside Hokkaido. (1) To examine the association between hypospadias and polymorphisms in steroid-metabolizing enzymes, Boys with S allele (G289S) of the HSD17B3 gene had an increased risk of hypospadias, especially distal types. Boys with V allele (L89V) of the SRD5A2 gene had a decreased risk of hypospadias, but not significant. (2) In mothers' heterozygote of Mspl polymorphism in the 3'-flanking region of CYP1A1 gene, odds ratio for hypospadias decreased significantly Similar tendency was observed in mothers' heterozygote of CYP1A1 gene for cryntorchidism, but not significant.