論文 - 詳細
| RRC ID | 86106 |
|---|---|
| 著者 | Tatebe T, Pham DQ, Ogura A, Inoue K. |
| タイトル | mTORC1-dependent suppression of autophagic activity in somatic cell nuclear transfer mouse embryos. |
| ジャーナル | Reproduction |
| Abstract |
IN BRIEF:The non-genomic factors responsible for developmental arrest in SCNT embryos remain poorly understood. Using live-cell fluorescence imaging, we revealed that autophagic activity is impaired in preimplantation SCNT embryos, possibly due to ectopic activation of the mTORC1 signaling pathway, providing new insights into cytoplasmic barriers to cloning efficiency. ABSTRACT:Activation of autophagy after fertilization is essential for mammalian embryonic development, as it supplies embryos with nutrients and energy. Somatic cell nuclear transfer (SCNT) embryos frequently exhibit developmental arrest, largely because of incomplete genomic reprogramming; however, the role of non-genomic factors remains unclear. Here, we investigated autophagy dynamics in mouse SCNT embryos using immunostaining and live-cell fluorescence imaging. In fertilized embryos, autophagy increased markedly from the late 2-cell stage and peaked at the morula stage. SCNT embryos followed a similar timeline but consistently showed reduced autophagic activity. Notably, the autophagic activity levels varied among SCNT embryos and positively correlated with their developmental potential. Attempts to enhance genomic reprogramming, including the removal of somatic histone methylation, did not restore autophagy. Instead, transcriptome analysis revealed ectopic activation of mTORC1 signaling as a likely cause of impaired autophagy. Consistently, treatment with an mTORC1 inhibitor successfully rescued autophagic activity in SCNT embryos. These findings identify a persistent autophagy defect during preimplantation development in SCNT embryos and suggest that modulation of non-genomic pathways, such as mTORC1 signaling, could improve SCNT efficiency. |
| 巻・号 | 170(6) |
| 公開日 | 2025-12-1 |
| DOI | 10.1530/REP-25-0338 |
| PII | e250338 |
| PMID | 41150827 |
| MeSH | Animals Autophagy* / physiology Blastocyst* / metabolism Embryo, Mammalian* / cytology Embryo, Mammalian* / metabolism Embryonic Development* Female Gene Expression Regulation, Developmental Mechanistic Target of Rapamycin Complex 1* / antagonists & inhibitors Mechanistic Target of Rapamycin Complex 1* / genetics Mechanistic Target of Rapamycin Complex 1* / metabolism Mice Nuclear Transfer Techniques* Signal Transduction |
| IF | 3.206 |
| リソース情報 | |
| 遺伝子材料 | pcDNA3-GFP-LC3-RFP-LC3 deltaG (RDB19804) |