Mitochondrial DNA mutation exacerbates female reproductive aging via impairment of the NADH/NAD<sup>+</sup> redox

Yang, Liang; Lin, Xiao-Lu; Tang, Huazhong; Fan, Yuting; Zeng, Sheng; Lu, Jia; Li, Yukun; Shi, Yanan; He, Shujing; Wang, Hao; Hu, Zhongliang; Gong, Xiao; Liang, Xiaoyan; Yang, Yi; Liu, Xingguo

doi:10.1111/acel.13206

Cited by 62 publications

(64 citation statements)

References 72 publications

(87 reference statements)

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“…Ovarian aging is related to reduced oocyte mtDNA content, and studies have shown that the mtDNA copy number per oocyte of young women is significantly higher than that of aged women or those of the same age with DOR ( Pasquariello et al, 2019 ). In addition, the accumulation of female mouse germline mtDNA mutations exacerbates ovarian aging and reduces lifespan ( Ross et al, 2014 ; Yang et al, 2020 ). Evidence for this is that the mitochondrial content of GCs and oocytes was significantly decreased in a mouse model of fragile X primary ovarian insufficiency ( Conca Dioguardi et al, 2016 ).…”

Section: Effects Of Oxidative Stress On Mitochondria In the Ovariesmentioning

confidence: 99%

The Role of Oxidative Stress and Natural Antioxidants in Ovarian Aging

et al. 2021

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The ovarian system comprises vital organs in females and is of great significance for the maintenance of reproductive potential and endocrine stability. Although complex pathogenesis undoubtedly contributes to ovarian aging, increasing attention is being paid to the extensive influence of oxidative stress. However, the role of oxidative stress in ovarian aging is yet to be fully elucidated. Exploring oxidative stress-related processes might be a promising strategy against ovarian aging. In this review, compelling evidence is shown that oxidative stress plays a role in the etiology of ovarian aging and promotes the development of other ovarian aging-related etiologies, including telomere shortening, mitochondrial dysfunction, apoptosis, and inflammation. In addition, some natural antioxidants such as quercetin, resveratrol, and curcumin have a protective role in the ovaries through multiple mechanisms. These findings raise the prospect of oxidative stress modulator-natural antioxidants as therapeutic interventions for delaying ovarian aging.

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Section: Effects Of Oxidative Stress On Mitochondria In the Ovariesmentioning

confidence: 99%

The Role of Oxidative Stress and Natural Antioxidants in Ovarian Aging

et al. 2021

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“…Consistent with this idea, enriched GO terms for downregulated genes included oxidoreductase activity, cellular respiration, and cellular response to stress ( S13 and S14 Figs). These pathways have been recently shown to be important for the generation of high quality oocytes in mammals [ 59 – 61 ].…”

Section: Discussionmentioning

confidence: 99%

Zebrafish Ski7 tunes RNA levels during the oocyte-to-embryo transition

et al. 2021

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Post-transcriptional regulation of gene expression is crucial during the oocyte-to-embryo transition, a highly dynamic process characterized by the absence of nuclear transcription. Thus, changes to the RNA content are solely dependent on RNA degradation. Although several mechanisms that promote RNA decay during embryogenesis have been identified, it remains unclear which machineries contribute to remodeling the maternal transcriptome. Here, we focused on the degradation factor Ski7 in zebrafish. Homozygous ski7 mutant fish had higher proportions of both poor quality eggs and eggs that were unable to develop beyond the one-cell stage. Consistent with the idea that Ski7 participates in remodeling the maternal RNA content, transcriptome profiling identified hundreds of misregulated mRNAs in the absence of Ski7. Furthermore, upregulated genes were generally lowly expressed in wild type, suggesting that Ski7 maintains low transcript levels for this subset of genes. Finally, GO enrichment and proteomic analyses of misregulated factors implicated Ski7 in the regulation of redox processes. This was confirmed experimentally by an increased resistance of ski7 mutant embryos to reductive stress. Our results provide first insights into the physiological role of vertebrate Ski7 as a post-transcriptional regulator during the oocyte-to-embryo transition.

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“…Regardless of the cell type, it is well known that mitochondrial DNA is more sensitive to mutation than nuclear DNA and that aging is an important risk factor. In mammalian oocytes, mitochondrial DNA mutations increase with age and are inversely correlated with oocyte quality [97][98][99]. In mice, oocyte mitochondrial DNA content increases during in vivo oogenesis without difference according to mice age [100].…”

Section: Discussionmentioning

confidence: 99%

Maternal age affects equine Day 8 embryo gene expression both in trophoblast and inner cell mass

Derisoud

Jouneau

Dubois³

et al. 2021

Preprint

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Background: Increased embryo loss as mares become older is a major consideration for breeders as older animals are currently used for reproduction in the equine industry. Lower embryo quality has been pointed out as partly responsible for this reduced fertility. Here, the effect of mare's age on blastocysts' gene expression was explored. Day 8 post ovulation embryos were collected by uterine flushing from multiparous young (YM, 6-year-old, N = 5) and older (OM, > 10-year-old, N = 6) non-nursing Saddlebred mares, inseminated with the semen of one stallion. Pure (TE_part) or inner cell mass enriched (ICMandTE) trophoblast were obtained by embryo bisection and paired end, non-oriented RNA sequencing (Illumina, NextSeq500) was performed on each hemi-embryo. To discriminate gene expression in the ICM from that in the TE, deconvolution (DeMixT R package) was used on the ICMandTE dataset. Differential expression was analyzed (DESeq2) with embryo sex and diameter as cofactors using a false discovery rate < 0.05 cutoff. Functional annotation and classification of differentially expressed genes and gene set enrichment analysis were also performed. Results: Maternal aging did not affect embryo recovery rate, embryo diameter nor total RNA quantity but modified gene expression in equine D8 embryos. The expression of genes in the ICM seemed to be more altered by maternal aging than in the TE. In both compartments, the expression of genes involved in mitochondrial function, translation and transcription due to chromatin modification were disturbed by maternal age. Mitosis, signaling and adhesion pathways and embryo development were particularly decreased in the ICM hemi-embryos from old mares. Finally, in TE, ion movement related genes were affected. Conclusions: This is the first study showing an effect of maternal age on gene expression in the equine blastocyst at Day 8 post ovulation. Maternal age, even for mares as young as 10 years old, disturbs mitosis, translation and transcription, cell signaling and adhesion as well as mitochondrial function and cell commitment of horse embryos. These perturbations may affect further embryo development and contribute to decreased fertility due to aging.

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Mitochondrial DNA mutation exacerbates female reproductive aging via impairment of the NADH/NAD⁺ redox

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 62 publications

References 72 publications

The Role of Oxidative Stress and Natural Antioxidants in Ovarian Aging

The Role of Oxidative Stress and Natural Antioxidants in Ovarian Aging

Zebrafish Ski7 tunes RNA levels during the oocyte-to-embryo transition

Maternal age affects equine Day 8 embryo gene expression both in trophoblast and inner cell mass

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Mitochondrial DNA mutation exacerbates female reproductive aging via impairment of the NADH/NAD+ redox

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 62 publications

References 72 publications

The Role of Oxidative Stress and Natural Antioxidants in Ovarian Aging

The Role of Oxidative Stress and Natural Antioxidants in Ovarian Aging

Zebrafish Ski7 tunes RNA levels during the oocyte-to-embryo transition

Maternal age affects equine Day 8 embryo gene expression both in trophoblast and inner cell mass

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Mitochondrial DNA mutation exacerbates female reproductive aging via impairment of the NADH/NAD⁺ redox