論文 - 詳細
| RRC ID | 81959 |
|---|---|
| 著者 | Sun F, Ali NN, Londoño-Vásquez D, Simintiras CA, Qiao H, Ortega MS, Agca Y, Takahashi M, Rivera RM, Kelleher AM, Sutovsky P, Patterson AL, Balboula AZ. |
| タイトル | Increased DNA damage in full-grown oocytes is correlated with diminished autophagy activation. |
| ジャーナル | Nat Commun |
| Abstract |
Unlike mild DNA damage exposure, DNA damage repair (DDR) is reported to be ineffective in full-grown mammalian oocytes exposed to moderate or severe DNA damage. The underlying mechanisms of this weakened DDR are unknown. Here, we show that moderate DNA damage in full-grown oocytes leads to aneuploidy. Our data reveal that DNA-damaged oocytes have an altered, closed, chromatin state, and suggest that the failure to repair damaged DNA could be due to the inability of DDR proteins to access damaged loci. Our data also demonstrate that, unlike somatic cells, mouse and porcine oocytes fail to activate autophagy in response to DNA double-strand break-inducing treatment, which we suggest may be the cause of the altered chromatin conformation and inefficient DDR. Importantly, autophagy activity is further reduced in maternally aged oocytes (which harbor severe DNA damage), and its induction is correlated with reduced DNA damage in maternally aged oocytes. Our findings provide evidence that reduced autophagy activation contributes to weakened DDR in oocytes, especially in those from aged females, offering new possibilities to improve assisted reproductive therapy in women with compromised oocyte quality. |
| 巻・号 | 15(1) |
| ページ | 9463 |
| 公開日 | 2024-11-1 |
| DOI | 10.1038/s41467-024-53559-w |
| PII | 10.1038/s41467-024-53559-w |
| PMID | 39487138 |
| PMC | PMC11530536 |
| MeSH | Aneuploidy Animals Autophagy* / genetics Chromatin / metabolism DNA Breaks, Double-Stranded* DNA Damage* DNA Repair* Female Mice Oocytes* / metabolism Swine |
| IF | 12.121 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 40 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC02975 |