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

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.

SUBMITTER: Liang K 

PROVIDER: S-EPMC8672779 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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

Liang Kuan K   Yao Liangyu L   Wang Shuxian S   Zheng Lu L   Qian Zhang Z   Ge Yifeng Y   Chen Li L   Cheng Xi X   Ma Rujun R   Li Chuwei C   Jing Jun J   Yang Yang Y   Yu Wanwan W   Xue Tongmin T   Chen Qiwei Q   Cao Siyuan S   Ma Jinzhao J   Yao Bing B  

Aging cell 20211109 12

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 in  ...[more]