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, 2021 12.
Article
em En
| MEDLINE
| ID: mdl-34751998
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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
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Proteínas de Ligação a RNA
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MicroRNAs
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Desenvolvimento Embrionário
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article