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

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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