| Project/Area Number |
11557120
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | THE UNIVERSITY OF TOKYO |
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Principal Investigator |
TSUTUMI Osamu THE UNIVERSITY OF TOKYO, DEPARTMENT OF OBSTETRICS AND GYNECOLOGY, PROFESSOR, 医学部附属病院, 教授 (60134574)
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| Co-Investigator(Kenkyū-buntansha) |
遠山 千春 国立環境研究所, 環境健康部, 部長 (10150872)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥12,200,000 (Direct Cost: ¥12,200,000)
Fiscal Year 2001: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1999: ¥5,400,000 (Direct Cost: ¥5,400,000)
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| Keywords | emhryo / low dose effect / in vitro fertilization / preimpaniation exposure / bisphenol A / blastocyst / estrogen receptor / endocrinc disruptor / ビスフェノールA / 多嚢胞性卵巣症候群 / 性差 / 内分泌撹乱化学物質 / 子宮内膜症 / 不妊症 / 卵胞液 / 内分泌撹乱物質 / Ahレセプター |
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| Research Abstract |
Bisphenol A (BPA), an estrogenic compound, is produced at more than 2 billion pounds/year and used in the production of epoxy resins and polycarbonate plastics. Human exposure to BPA may be so important that we investigated human exposure to bisphenol A and measured serum BPA concentrations and analyzed the interrelation of BPA with sex-related hormones. BPA was detected in all human sera by a novel enzyme-linked immunosorbent assay. Serum BPA concentrations were significantly higher in normal men (1.49±0.11 ng/ml; p<0.01) and in women with polycystic ovary syndrome (1.04±0.10 ng/ml; p<0.05) compared with normal women (0.64±0.10 ng/ml). These findings showed that there are gender differences in serum BPA concentrations, possibly due to differences in the androgen-related metabolism of BPA. We applied the preimplantation embryo development model to examine the effect of BPA which has been shown to 'exert effects similar to low-dose effects of endocrine disrupters. For the control group
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that was not exposed to BPA, the rate of in vitro development from two-cell embryos to eight-cell embryos was approximately 88 % (334/378) at 24 hr of culture. This rate was significantly increased by exposure to 3 nM BPA (94 %; 172/182) compared with the rate for the control group. Similarly, the rates of development to the blastocyst stage in 48-hr cultures of two-cell embryos were significantly increased by exposure to BPA at concentrations of 1 nM (69.0 %; 207/300) and 3 nM (69.2 %; 126/182) compared with the unexposed control embryos (58.7 %; 222/378). On the other hand, the frequency of development to the blastocyst stage at 48 hr was significantly decreased by exposure to 100 μM BPA (3 1.2 %; 93/298) compared with that for the control group, although the development to eight-cell embryos at 24 hr was not inhibited by 100 μM BPA. To examine the quality of the embryos -exposed during preimplantation development, we transferred the blastocysts developed with or without BPA exposure to uterine horns of pseudopregnant recipient mice that did not receive BPA treatment. The number of pups in a litter did not differ significantly between mice with and without BPA treatment during the preimplantation period; the pups had similar sex ratios and body weights at birth. At weaning on postnatal day 21, it was found that siblings treated with 1 nM and 100 μM BPA were significantly heavier than controls. Relative to controls without BPA treatment, the weaning weight of siblings exposed to 1 no BPA increased by 39 % and that of siblings with 100 μM exposure increased by 34%. It is of interest to note that not only in utero exposure, but also preimplantation embryo exposure to an environmental dose of BPA, alters postnatal development. Less
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