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

First Author  Liang K Year  2021
Journal  Aging Cell Volume  20
Issue  12 Pages  e13508
PubMed ID  34751998 Mgi Jnum  J:316775
Mgi Id  MGI:6841044 Doi  10.1111/acel.13508
Citation  Liang K, et al. (2021) miR-125a-5p increases cellular DNA damage of aging males and perturbs stage-specific embryo development via Rbm38-p53 signaling. Aging Cell 20(12):e13508
abstractText  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.
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