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

作者:Liang, Kuan; Yao, Liangyu; Wang, Shuxian; Zheng, Lu; Qian, Zhang; Ge, Yifeng; Chen, Li; Cheng, Xi; Ma, Rujun; Li, Chuwei; Jing, Jun; Yang, Yang; Yu, Wanwan; Xue, Tongmin; Chen, Qiwei; Cao, Siyuan; Ma, Jinzhao*; Yao, Bing*
来源:AGING CELL, 2021, 20(12): e13508.
DOI:10.1111/acel.13508

摘要

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.

  • 单位
    南京大学; 南方医科大学; 1