Dose-dependent acceleration in the delayed effects of neonatal oral exposure to low-dose 17α-ethynylestradiol on reproductive functions in female Sprague-Dawley rats
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- Shirota Mariko
- Laboratory of Comparative Toxicology, School of Veterinary Medicine
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- Kawashima Jun
- Laboratory of Comparative Toxicology, School of Veterinary Medicine
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- Nakamura Tomohiro
- Laboratory of Comparative Toxicology, School of Veterinary Medicine
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- Kamiie Junichi
- Laboratory of Veterinary Pathology, Azabu University
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- Shirota Kinji
- Laboratory of Veterinary Pathology, Azabu University Research Institute of Biosciences, Azabu University
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- Yoshida Midori
- Division of Pathology, National Institute of Health Sciences
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抄録
Xenoestrogen exposure during the critical period of sexual differentiation of the brain causes delayed effects on female reproduction. We investigated the internal dose of orally administered ethynylestradiol (EE) during the critical period and its delayed effects by administering 0 (vehicle control), 0.4, or 2 μg/kg EE to female Sprague-Dawley rats for 5 days from postnatal day (PND) 1. Determination of serum EE level 24 hr after the initial dosing and 6 and 24 hr after the final dosing of 2 μg/kg indicated that the administered EE entered the circulation and cleared after every administration. Although the treatment did not affect physical development, including growth, eyelid opening, and vaginal opening, the estrous cycle was arrested from postnatal week (PNW) 12 even with 0.4 μg/kg EE, with an inverse correlation between doses and arresting ages. Although ovarian morphology at PNW 22-23 indicated that the treatment caused long-term anovulation and cystic follicle formation, the number of primordial follicles at PNW 22-23 was similar among the groups. Because this number was lower than that at PND 10 in all groups, primordial follicles may have been consumed under long-term anovulation. The treatment also caused other abnormalities, including mammary gland hyperplasia, increase in pituitary and liver weights, and decrease in the uterine weight. Because the highest circulating EE level in the 2 μg/kg-treated neonates is considered to be comparable to the physiological range of estradiol-17β, we concluded that a slight increase in the circulating estrogens during the neonatal period exerts irreversible delayed effects.
収録刊行物
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- The Journal of Toxicological Sciences
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The Journal of Toxicological Sciences 40 (6), 727-738, 2015
一般社団法人 日本毒性学会
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詳細情報 詳細情報について
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- CRID
- 1390001204903396608
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- NII論文ID
- 130005108876
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- NII書誌ID
- AN00002808
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- ISSN
- 18803989
- 03881350
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- NDL書誌ID
- 026971332
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- PubMed
- 26558453
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可