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

人类在胎儿或出生后发育过程中激素调节的紊乱被认为会对健康产生不利影响。但内分泌干扰物对人类的不利影响尚不清楚，也难以检测。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记和DNA微阵列分析对评估胎儿内分泌干扰物暴露的重要性日益增加。在此，我们总结了我们在日本胎儿内分泌干扰物暴露、睾丸体重的时间变化以及我们在男性生殖器官中内分泌干扰物改变基因表达分析方面的新项目。a .胎儿内分泌干扰物暴露：我们的研究已获得千叶大学“医学生物伦理学大会”的批准。我们在人脐带和脐带血清中检测到二恶英（pcdd + pcdf +CO-PCBs）、多氯联苯、DDTs、DDEs、endostulfan、六氯环己烷（HCH）、氯丹、多氯联苯（HCB）、重金属（Cd和Pb）、双酚A和植物雌激素（染料木素、大豆苷元和雌马酚）。通过对脐带组织和脐带血清的研究，我们发现日本胎儿暴露于几种edb。b .男性生殖障碍的细微变化：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)峰值体重普遍变得更高，直到1960出生年之后开始出现峰值体重下降。产后暴露己烯雌酚（DES）可引起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）表达谱的长期变化。通过基因芯片分析，我们检测了小鼠睾丸中DES、染料木素或双酚a诱导/抑制的大量基因。新生儿暴露于DES、染料木素和双酚A会改变成年小鼠睾丸中许多基因的表达。我们的结果表明，DNA微阵列分析是一种有效的方法，通过它可以同时检测到大量的改变基因。我们必须研究更多关于评估胎儿暴露和影响内分泌干扰物

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