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Studies on adverse effects of endocrine disruptors on male reproduction and next generation.

内分泌干扰物对男性生殖及下一代不良影响的研究。

基本信息

批准号：
11839013
负责人：
MORI Chisato
金额：
$ 2.3万
依托单位：
Chiba University (2000)Kyoto University (1999)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

Disturbances of hormonal regulation during fetal or postnatal development in humans have been thought to induce adverse effects on health. But adverse effects of endocrine disruptors on humans are less clear, and difficult to detect. Therefore, we have continued to investigate fetal exposure to endocrine disruptors in Japan by analyzing umbilical cords or cord serum. Our recent studies indicate the increasing importance of biological markers and DNA microarray analysis for assessing fetal exposure of endocrine disruptors. Here, we summarize our data on fetal exposure of endocrine disruptors in Japan, temporal changes of testis-weight and our new projects on analysis of gene expression changed by endocrine disruptors in male reproductive organs.A.Fetal exposure of endocrine disruptors :Our studies have been approved by the "Congress of Medical Bioethics" of Chiba University.We detected dioxins (PCDDs+PCDFs+CO-PCBs), PCBs, DDTs, DDEs, endostulfan, hexachlorocyclohexane (HCH), chlordanes, … More hexachlorobenzene (HCB), heavy metals (Cd and Pb), bisphenol A and phytoestrogens (genistein, daidzein and equol) in human umbilical cords and cord serum. By studying umbilical cord tissue and cord serum, we found that fetuses in Japan were exposed to several EDs.B.Subtle male reproductive disorders : Temporal changes of testis-weightOur analyses indicates that the development of testis-weight over the last fifty years has followed two marked phenomena : (a) the age at which testis-weight reaches its maximum has become younger, and (b) the weight at peak had become generally higher, until a decline in peak-weight beginning after 1960 birth years.C.Analysis of gene-expression changed by endocrine disruptors in male reproductive organs :1. Postnatal exposure of diethylstilbestrol (DES) induces the long-term changes of morphological structure of epididymal ducts, estrogen receptor and lactoferrin (estrogen responsive gene) expression pattern in mouse epididymis.2. Using cDNA microarray antalysis, we examined a large number of genes induced/suppressed by DES, Genistein or Bisphenol A treatment in mouse testis. Neonatal exposure of DES, Genistein and Bisphenol A causes altered expression of many genes in adult mouse testis. Our results indicate that DNA microarray analysis is useful method by which a large number of altered genes are simultaneously detected.We must investigate more about assessing fetal exposure and effects of endocrine disruptors Less

人类在胎儿或出生后发育过程中荷尔蒙调节的紊乱被认为会对健康造成不利影响。但内分泌干扰物对人类的不利影响不太清楚，也很难检测到。因此，我们继续通过分析脐带或脐带血清来调查日本胎儿暴露于内分泌干扰物的情况。我们最近的研究表明，生物标志物和DNA微阵列分析在评估胎儿内分泌干扰物暴露方面的重要性日益增加。在这里，我们总结了我们关于日本胎儿暴露于内分泌干扰物的数据、睾丸重量的时间变化以及我们在男性生殖组织中分析内分泌干扰物改变基因表达的新项目。A.胎儿内分泌干扰物的暴露：我们的研究已经得到千叶大学医学生物伦理学会议的批准。我们检测到二恶英(PCDDs+PCDFS+CO-PCbs)、多氯联苯(PCbs)、DDT、DDES、硫丹、六六六、氯丹、…人脐血和脐血中的六氯苯(HCB)、重金属(Cd和Pd)、双酚A和植物雌激素(染料木素、大豆苷元和马酚)含量较高。通过对脐带组织和脐带血清的研究，我们发现日本的胎儿暴露于几种ED。B.男性生殖障碍：睾丸重量的时间变化我们的分析表明，在过去的50年里，睾丸重量的发展遵循了两个显著的现象：(A)睾丸重量达到最大值的年龄变得更年轻，(B)峰值重量普遍变高，直到1960年出生后体重峰值开始下降。C.男性生殖器官内分泌干扰物改变基因表达的分析：1.出生后暴露于己烯雌酚(DES)可诱导小鼠附睾管形态结构、雌激素受体和乳铁蛋白(雌激素反应基因)表达模式的长期变化。利用基因芯片技术，我们检测了DES、Genistein和双酚A对小鼠睾丸的大量诱导/抑制基因。新生小鼠暴露于DES、Genistein和双酚A可引起成年小鼠睾丸中许多基因表达的改变。我们的结果表明，DNA微阵列分析是一种有用的方法，通过它可以同时检测大量改变的基因。我们需要更多地研究评估胎儿暴露和内分泌干扰物的影响