Polyamine metabolite spermidine rejuvenates oocyte quality by enhancing mitophagy during female reproductive aging

亚精胺 卵母细胞 粒体自噬 生物 不育 多胺 男科 内分泌学 医学 细胞生物学 怀孕 遗传学 生物化学 胚胎 细胞凋亡 自噬
作者
Yu Zhang,Jie Bai,Zhaokang Cui,Yu Liu,Qian Gao,Yun Miao,Bo Xiong
出处
期刊:Nature Aging 卷期号:3 (11): 1372-1386 被引量:16
标识
DOI:10.1038/s43587-023-00498-8
摘要

Advanced age is a primary risk factor for female infertility due to reduced ovarian reserve and declining oocyte quality. However, as an important contributing factor, the role of metabolic regulation during reproductive aging is poorly understood. Here, we applied untargeted metabolomics to identify spermidine as a critical metabolite in ovaries to protect oocytes against aging. In particular, we found that the spermidine level was reduced in ovaries of aged mice and that supplementation with spermidine promoted follicle development, oocyte maturation, early embryonic development and female fertility of aged mice. By microtranscriptomic analysis, we further discovered that spermidine-induced recovery of oocyte quality was mediated by enhancement of mitophagy activity and mitochondrial function in aged mice, and this mechanism of action was conserved in porcine oocytes under oxidative stress. Altogether, our findings suggest that spermidine supplementation could represent a therapeutic strategy to ameliorate oocyte quality and reproductive outcome in cis-gender women and other persons trying to conceive at an advanced age. Future work is needed to test whether this approach can be safely and effectively translated to humans. Advanced age is a primary risk factor for female infertility due to declining oocyte quantity and quality. Here Yu Zhang et al. report that supplementation with spermidine rejuvenates the quality of oocytes from aged mice at least in part by enhancing mitophagy and mitochondrial function.
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