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miR-125a-5p 通过 Rbm38-p53 信号增加衰老雄性细胞的 DNA 损伤，并扰乱胚胎发育的特定阶段。

miR-125a-5p increases cellular DNA damage of aging males and perturbs stage-specific embryo development via Rbm38-p53 signaling.

机构信息

Center of Reproductive Medicine, Nanjing Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, China.

Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

出版信息

Aging Cell. 2021 Dec;20(12):e13508. doi: 10.1111/acel.13508. Epub 2021 Nov 9.

DOI:10.1111/acel.13508
PMID:34751998
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8672779/
Abstract

An increasing number of men are fathering children at an older age than in the past. While advanced maternal age has long been recognized as a risk factor for adverse reproductive outcomes, the influence of paternal age on reproduction is incompletely comprehended. Herein, we found that miR-125a-5p was upregulated in the sperm of aging males and was related to inferior sperm DNA integrity as an adverse predictor. Moreover, we demonstrated that miR-125a-5p suppressed mitochondrial function and increased cellular DNA damage in GC2 cells. We also found that miR-125a-5p perturbed embryo development at specific morula/blastocyst stages. Mechanistically, we confirmed that miR-125a-5p disturbed the mitochondrial function by targeting Rbm38 and activating the p53 damage response pathway, and induced a developmental delay in a p21-dependent manner. Our study revealed an important role of miR-125a-5p in sperm function and early embryo development of aging males, and provided a fresh view to comprehend the aging process in sperm.

摘要

越来越多的男性比过去更晚生育孩子。虽然高龄产妇一直被认为是不良生殖结局的一个风险因素，但父亲年龄对生殖的影响还不完全清楚。在这里，我们发现衰老雄性的精子中 miR-125a-5p 上调，并且作为不良预测因子与较差的精子 DNA 完整性有关。此外，我们证明 miR-125a-5p 抑制 GC2 细胞中的线粒体功能并增加细胞 DNA 损伤。我们还发现 miR-125a-5p 在特定的桑葚胚/囊胚阶段扰乱胚胎发育。从机制上讲，我们通过靶向 Rbm38 并激活 p53 损伤反应途径证实 miR-125a-5p 通过干扰线粒体功能，并以 p21 依赖的方式诱导发育延迟。我们的研究揭示了 miR-125a-5p 在衰老雄性精子功能和早期胚胎发育中的重要作用，并为理解精子衰老过程提供了新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c333/8672779/0e57c5e7982f/ACEL-20-e13508-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c333/8672779/567989aa9417/ACEL-20-e13508-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c333/8672779/ff2660ad672d/ACEL-20-e13508-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c333/8672779/6cb317e580dc/ACEL-20-e13508-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c333/8672779/579e95e79622/ACEL-20-e13508-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c333/8672779/0e57c5e7982f/ACEL-20-e13508-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c333/8672779/567989aa9417/ACEL-20-e13508-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c333/8672779/ff2660ad672d/ACEL-20-e13508-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c333/8672779/6cb317e580dc/ACEL-20-e13508-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c333/8672779/579e95e79622/ACEL-20-e13508-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c333/8672779/0e57c5e7982f/ACEL-20-e13508-g002.jpg

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