miR-125a-5p increases cellular DNA damage of aging males and perturbs stage-specific embryo development via Rbm38-p53 signaling.
miR-125a-5p increases cellular DNA damage of aging males and perturbs stage-specific embryo development via Rbm38-p53 signaling.
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作者：
Liang K;Yao L;Wang S;Zheng L;Qian Z;Ge Y;Chen L;Cheng X;Ma R;Li C;Jing J;Yang Y;Yu W;Xue T;Chen Q;Cao S;Ma J;Yao B
与过去相比，越来越多的男性在更大的年龄生下了孩子。虽然高龄产妇长期以来一直被认为是不良生殖结局的危险因素，但对父方年龄对生殖的影响还没有完全了解。在这里，我们发现miR-125a-5p在老年男性精子中表达上调，并与精子DNA完整性差有关，作为一个不利的预测因子。此外，我们还发现miR-125a-5p抑制了GC2细胞的线粒体功能，增加了细胞DNA损伤。我们还发现miR-125a-5p干扰了特定桑拿期/囊胚期的胚胎发育。从机制上，我们证实miR-125a-5p通过靶向Rbm38和激活p53损伤反应通路来干扰线粒体的功能，并以p21依赖的方式诱导发育延迟。本研究揭示了miR-125a-5p在老年男性精子功能和早期胚胎发育中的重要作用，为理解精子的衰老过程提供了新的视角。MIR-125a-5p在老年男性精子中升高。MiR-125a-5p通过靶向Rbm38，激活P53损伤反应通路，抑制线粒体功能，增加细胞DNA损伤。MiR-125a-5p以p21依赖的方式干扰特定桑拿期/囊胚期的胚胎发育。
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. miR‐125a‐5p was increased in the sperm of aging males. miR‐125a‐5p suppressed mitochondrial function and increased cellular DNA damage by targeting Rbm38 and activating p53 damage response pathway. miR‐125a‐5p perturbed embryo development at specific morula/blastocyst stages in a p21‐dependent manner.
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64.5
作者：
López-Otín C;Blasco MA;Partridge L;Serrano M;Kroemer G
通讯作者：
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通讯作者：
Piasecka, Malgorzata
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