@article{oai:az.repo.nii.ac.jp:00004688,
 author = {代田, 欣二 and 村上, 賢 and 赤堀, 文昭 and 代田, 眞理子 and 櫻田, 陽右 and 早坂, 恵子 and 笠井, 豊 and 澤井, 政善 and Shirota, Kinji and Murakami, Masaru and Akahori, Humiaki and Shirota, Mariko and Sakurada, Yosuke and Hayasaka, Keiko and Kasai, Yutaka and Sawai, Masayoshi},
 journal = {麻布大学雑誌, Journal of Azabu University},
 month = {Mar},
 note = {妊娠15日のSD系ラットにコーン油,あるいはPCB126を10,30または100μg/kgの用量で経口投与し,5,10,15,21,24日齢の雌出生子の卵巣におけるAhR,CYP1A1,inhibinαサブユニットおよびβA,βBサブユニット,aromatase,FSH受容体,LH受容体,c-kit,BMP-15,GDF-9の遺伝子発現量を定量した。残りの一部の動物は,膣開口日まで飼育して,初回排卵数を測定した。その結果,卵巣重量は30μg/kg以上で,初回排卵数は,100μg/kgで対照群と比較して,有意な減少が認められた。CYP1A1は,暴露動物において5日齢で既に有意な増加が認められ,その後次第に減少した。inhibinβA,βBサブユニット,aromataseおよびLH受容体の遺伝子発現量は,30または100μg/kg動物で10日齢以降に,またinhibinαの遺伝子は5日齢から,同日齢の対照と比べて有意な低値を示した。一方,GDF-9,BMP-15の各遺伝子は,15日齢以降の100μg/kg群で発現量は高値であった。本実験の結果から,PCB126の暴露が幼若期卵巣における卵胞を構成する体細胞に発現する遺伝子の発現量を減少させること,また,発育開始後の卵胞がPCB暴露の標的となっていることが示唆された。また,24日齢のSD系雌ラットにコーン油,または160,320μg/kgのPCB126を経口投与し,投与後24時間にPMSG 5IUを皮下投与して,その約76時間後に排卵を検査した。一部の動物はPCB126投与時(0h),6h,24h(PMSG投与時),72hに解剖した。肝臓及び胸腺の重量は,それぞれ24h,72hから対照群と比較して有意に減少し,卵巣には6hをピークとしてCYP1A1 mRNAの増加が認められことから,PCB126はPMSG投与前から卵巣に影響を及ぼしていることが明らかとなった。また,卵巣におけるinhibinα,aromataseならびにFSH及びLHの各受容体mRNAsの発現量,卵巣重量,および排卵にはPCB126の影響が認められなかった。以上から,PCB126暴露時期および暴露期間が卵巣に及ぼす影響の有無に重要で,この時期の大型の胞状卵胞はPCBの標的ではないことが示唆された。, The pregnant female SD rats were single-administered orally corn oil or 10, 30 and 100μg/kg B.W. of PCB126 on gestational day 15 (GD 15). Their offspring were sacrificed on the post-natal day (PND) 5, 10, 15, 21 and 24, and the ovaries were collected for quantification of the gene expression of CYP1A1, AhR, inhibins (α, βA and βB), FSH receptor (FSHR), LH receptor (LHR), aromatase, GDF-9, BMP-15, c-kit and kit ligand. The remaining offspring of each dam were sacrificed at the day of virginal opening (VO) and the number of oocytes shed was counted. The gene expression of CYP1A1 in the ovaries of exposed offspring was significantly increased on PND 5 with dose dependent manner and decreased with age. Inhibin α subunit mRNA was decreased from PND 5. The gene expression of βA and βB subunits, aromatase and LHR was also decreased in 30 and 100μg/kg-dosed groups from PND 10. The levels of mRNA of GDF-9 and BMP-15 in the ovaries of 100μg/kg-exposed group were higher than those in controls. Ovarian weight of 30 and 100μg/kg-dosed groups at PND 15 and PND 24 were lower than that of controls. In the 100μg/kg-dosed group the number of oocytes shed at the first ovulation was lower than that in the control group. These results suggest that the exposure to PCB126 decreases the levels of gene expression in the somatic cells composing ovarian follicles before puberty and the ovarian follicles entering into developing stage might be the target of PCB126 toxicity. Furthermore, female SD rats aged 24 days were single-administered orally corn oil or 160, 320μg/kg B.W. of PCB126. The rats were also injected subcutaneously 5IU of PMSG 24 hours after PCB126 administration to induce ovulation. Then, the number of shedding oocytes induced by PMSG was counted 76 hours after PMSG injection. Some rats were sacrificed 0, 24 and 72 hours after PCB126 administration. The weight of liver and thymus were significantly decreased 24 and 72 hours after PCB126 exposure, respectively. The level of CYP1A1 mRNA in the ovaries significantly increased and peaked 6 hours after PCB126 administration. These indicate that PCB126 affected the ovary before PMSG treatment. However, there were no effects of PCB126 exposure on the level of gene expression of inhibinα, aromatase, FSHR and LHR in the ovaries. These results suggest that the timing of PCB126 exposure might be critical for ovarian toxicity and the large follicles in the ovary at this age might not be the targets of PCB126., 麻布大学ハイテク・リサーチ・センター研究プロジェクト 研究サブ・グループ1, P(論文), 特集, application/pdf, FEATURE ARTICLES},
 pages = {234--236},
 title = {Co-PCBsの次世代に及ぼす影響},
 volume = {9/10},
 year = {2005},
 yomi = {シロタ, キンジ and ムラカミ, マサル and アカホリ, フミアキ and シロタ, マリコ and サクラダ, ヨウスケ and ハヤサカ, ケイコ and カサイ, ユタカ and サワイ, マサヨシ}
}