Dataset Information

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

ACCESS DATA

Publications

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]

PMID: 34751998

Similar Datasets

Project description:Maximal oxygen uptake and exercise performance typically decline with age. However, there are indications of preserved vascular function and blood flow regulation during arm exercise. Yet, it is unknown if this potential physiological preservation with age is mirrored in peripheral metabolic capacity and V̇o2/W ratio. Thus, to investigate the effects of aging in the arms, we measured metabolic and vascular responses to 6-min bouts of dynamic handgrip exercise at 40% and 80% of maximal work rate (WRmax) in 11 young (26 ± 2 yr) and 12 old (80 ± 6 yr) males, applying Doppler-ultrasound combined with blood samples from a deep forearm vein. At baseline, the old had a larger arterial diameter compared with young (P < 0.001). During exercise, the two groups reached the same WRmax. V̇o2, blood flow, and oxygen supply were higher (40%WRmax; 80%WRmax, all P < 0.01), and arteriovenous oxygen difference was lower (80%WRmax, P < 0.02), in old compared with young. Old also had a higher oxygen excess at 80%WRmax (P < 0.01) than young, whereas no difference in muscle diffusion or oxygen extraction was detected. Only young exhibited an increase in intensity-induced arterial dilation (P < 0.05), and they had a lower mean arterial pressure than old at 80%WRmax (P < 0.001). V̇o2/W (40%WRmax; 80%WRmax) was reduced in old compared with young (both P < 0.05). In conclusion, in old and young males with a similar handgrip WRmax, old had a higher V̇o2 during 80%WRmax intensity, achieved by an increased blood flow. This may be a result of the available cardiac output reserve, compensating for reduced work efficiency and attenuated vascular response observed in old.NEW & NOTEWORTHY Contrasting the typically observed decline in V̇o2max with age, the current study reveals an age-related increase in forearm metabolic capacity during handgrip exercise in old, mediated by an increased forearm blood flow. Exercise with a small muscle mass in arms, where central components of the oxygen transport are not limiting, allows old to attain a similar maximal work rate as young despite their increased V̇o2/W ratio.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets