Influence of endocrine disrupting chemicals on the health of future generation

[妊娠妇女队列研究]（1）受试者为妊娠26 - 35周的妊娠妇女，截至2004年2月招募340例。（2）对孕妇进行问卷调查，内容包括饮食、家庭环境等。(3)他们的婴儿通过神经行为测试进行评估：6个月和18个月大的贝利婴儿发育量表，7个月大的费根婴儿智力测试。(4)测定孕妇及新生儿血清FT 4、TSH水平。(5)测定脐血IgE水平。(6)检测了100名孕妇体内二恶英和多氯联苯的含量。对15对孕妇和脐带血样本的全氟辛烷磺酸水平进行了测量。全氟辛烷磺酸在人体内的蓄积量可以测量，母体血液和脐带血中的全氟辛烷磺酸浓度之间存在高度相关性。(7)研究了外源物代谢酶基因多态性。(8)研究胎盘中P450的表达和内分泌干扰物的暴露。(9)这些婴儿将被随访数年，研究内分泌干扰物对其神经行为发育和过敏性疾病的影响。[尿道下裂和隐睾的病例对照研究]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的病例对照研究。(1)为了研究尿道下裂与类固醇代谢酶多态性之间的关系，具有HSD 17 B3基因S等位基因（G289 S）的男孩尿道下裂的风险增加，尤其是远端型。SRD 5A 2基因V等位基因（L 89 V）的男孩尿道下裂的风险降低，但不显著。(2)CYP 1A 1基因3 ′侧翼区Msp 1多态性杂合子的母亲患尿道下裂的优势比显著降低。CYP 1A 1基因3 ′侧翼区Msp 1多态性杂合子的母亲患隐睾的优势比也有类似趋势，但不显著。

[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.