| アイテムタイプ |
itemtype_ver1(1) |
| 公開日 |
2024-07-03 |
| タイトル |
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タイトル |
Brca2^(p.T1942fs/+) dissipates ovarian reserve in rats through oxidative stress in follicular granulosa cells |
|
言語 |
en |
| 著者 |
Tanaka, Hideaki
Motooka, Yashiro
Maeda, Yuki
Sonehara, Reina
Nakamura, Tomoko
Kajiyama, Hiroaki
Mashimo, Tomoji
Toyokuni, Shinya
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| アクセス権 |
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アクセス権 |
open access |
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アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 権利 |
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|
権利情報 |
This is an Accepted Manuscript of an article published by Taylor & Francis Group in Free Radical Research on 29/02/2024, available online: http://www.tandfonline.com/10.1080/10715762.2024.2320405. |
|
言語 |
en |
| 内容記述 |
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内容記述タイプ |
Abstract |
|
内容記述 |
Pathogenic variants of BRCA1/2 constitute hereditary breast and ovarian cancer (HBOC) syndrome, and BRCA1/2 mutant is a risk for various cancers. Whereas the clinical guideline for HBOC patients has been organized for the therapy and prevention of cancer, there is no recommendation on the female reproductive discipline. Indeed, the role of BRCA1/2 pathogenic variants in ovarian reserve has not been established due to the deficiency of appropriate animal models. Here, we used a rat model of Brca2^(p.T1942fs/+) mutant of Sprague-Dawley strain with CRISPR-Cas9 editing to evaluate ovarian reserve in females. Fertility and ovarian follicles were evaluated and anti-Müllerian hormone (AMH) was measured at 8–32 weeks of age with a comparison between the wild-type and the mutant rats (MUT). MUT revealed a significantly smaller number of deliveries with fewer total pups. Furthermore, MUT showed a significant decrease in primordial follicles at 20 weeks and a low AMH level at 28 weeks. RNA-sequencing of the ovary at 10 weeks detected acceleration of the DNA damage repair pathway, which was accompanied by oxidative stress-induced DNA double-strand breaks, a decrease in PTEN, and an increase in mTOR in follicular granulosa cells. In conclusion, Brca2^(p.T1942fs/+) dissipates primordial follicles via early activation of granulosa cells through oxidative stress, leading to earlier termination of fertility. |
|
言語 |
en |
| 出版者 |
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出版者 |
Taylor & Francis |
|
言語 |
en |
| 言語 |
|
|
言語 |
eng |
| 資源タイプ |
|
|
資源タイプresource |
http://purl.org/coar/resource_type/c_6501 |
|
タイプ |
journal article |
| 出版タイプ |
|
|
出版タイプ |
AM |
|
出版タイプResource |
http://purl.org/coar/version/c_ab4af688f83e57aa |
| 関連情報 |
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|
関連タイプ |
isVersionOf |
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|
識別子タイプ |
DOI |
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|
関連識別子 |
https://doi.org/10.1080/10715762.2024.2320405 |
| 収録物識別子 |
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収録物識別子タイプ |
PISSN |
|
収録物識別子 |
1071-5762 |
| 書誌情報 |
en : Free Radical Research
巻 58,
号 2,
p. 130-143,
発行日 2024-02-29
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| ファイル公開日 |
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|
日付 |
2025-02-28 |
|
日付タイプ |
Available |
Tanaka_FFR_revised_102323.pdf (35.1 MB)
