粒体自噬
胚胎干细胞
胚胎发生
细胞生物学
铜
纳米颗粒
新陈代谢
纳米技术
生物
胚胎
材料科学
化学
自噬
生物化学
细胞凋亡
冶金
基因
作者
Yunyao Luo,Xi Zeng,Dai Xue,Tian Yin,Jie Li,Qi Zhang,Qiang Dong,Lifeng Qin,Guoning Huang,Qi Gu,Jianyu Wang,Jingyu Li
出处
期刊:ACS Nano
[American Chemical Society]
日期:2024-11-02
标识
DOI:10.1021/acsnano.4c09734
摘要
Copper oxide nanoparticles (CuONPs) have been widely applied, posing potential risks to human health. Although the toxicity of CuONPs on the liver and spleen has been reported, their effects on reproductive health remain unexplored. In this study, we investigate the effects of CuONPs on embryonic development and their potential mechanisms. Our results demonstrate that CuONPs exposure impairs mouse preimplantation embryonic development, particularly affecting the morula-to-blastocyst transition. Additionally, CuONPs were found to reduce the pluripotency of the inner cell mass (ICM) and mouse embryonic stem cells (mESCs). Mechanistically, CuONPs block autophagic flux and impair mitophagy, leading to the accumulation of damaged mitochondria. This mitochondrial dysfunction leads to reduced tricarboxylic acid (TCA) cycle activity and decreased α-ketoglutarate (α-KG) production. Insufficient α-KG induces the failure of DNA demethylation, reducing corresponding chromatin accessibility and consequently inhibiting ICM-specific genes expressions. Similar reduced development and inhibitions of pluripotency gene expression were observed in CuONPs-treated human blastocysts. Moreover, in women undergoing assisted reproductive technology (ART), a negative correlation was found between urinary Cu ion concentrations and clinical outcomes. Collectively, our study elucidates the mitophagy-mediated metabolic mechanisms of CuONPs embryotoxicity, improving our understanding of the potential reproductive toxicity associated with it.
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