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Increasing ovarian NAD+ levels improve mitochondrial functions and reverse ovarian aging.
Free Radical Biology and Medicine ( IF 7.4 ) Pub Date : 2020-05-31 , DOI: 10.1016/j.freeradbiomed.2020.05.003
Qingling Yang 1 , Luping Cong 1 , Yujiao Wang 1 , Xiaoyan Luo 1 , Hui Li 1 , Huan Wang 1 , Jing Zhu 1 , Shanjun Dai 1 , Haixia Jin 1 , Guidong Yao 1 , Senlin Shi 1 , Aaron J Hsueh 2 , Yingpu Sun 1
Affiliation  

Loss of follicles together with decreased oocyte quality and quantity contribute to age-associated ovarian senescence and infertility. Although underlying mechanisms for ovarian senescence are still unknown, mitochondrial dysfunctions have been reported. Here, we showed age-dependent decreases in ovarian Nicotinamide Adenine Dinucleotide (NAD+) levels in mice whereas supplementing aging mice with nicotinamide riboside (NR), an NAD+ precursor, increased ovarian NAD+ content. We found that increases in ovarian NAD+ levels in aging mice led to increased number of ovarian follicles and ovulatory potential as well as increased live birth rate. NR supplementation also reduced levels of reactive oxygen species and decreased spindle anomalies in aging oocytes, together with increased mitochondrial membrane potential (ΔΨm) and decreased mitochondrial clustering. In addition, NR supplementation improved ovarian mitochondrial energy metabolism. Our data suggested that supplementation with NAD+ precursors in vivo and in vitro could be potential therapeutic approaches for treating age-related ovarian infertility.



中文翻译:

卵巢NAD +水平的提高可改善线粒体功能并逆转卵巢衰老。

卵泡的丧失以及卵母细胞质量和数量的下降会导致与年龄相关的卵巢衰老和不育。尽管尚不清楚卵巢衰老的潜在机制,但已经报道了线粒体功能障碍。在这里,我们显示了小鼠中卵巢烟酰胺腺嘌呤二核苷酸(NAD +)水平的年龄依赖性降低,而给衰老小鼠补充NAD +前体烟酰胺核糖(NR)则增加了卵巢NAD +含量。我们发现卵巢NAD +增加衰老小鼠体内的血红蛋白水平导致卵巢卵泡数目和排卵潜能的增加以及活产率的增加。NR补充还降低了衰老的卵母细胞中活性氧的含量,减少了纺锤体异常,并增加了线粒体膜电位(ΔΨm)和线粒体簇集。另外,NR补充改善了卵巢线粒体能量代谢。我们的数据表明,体内体外补充NAD +可能是治疗与年龄相关的卵巢不育症的潜在治疗方法。

更新日期:2020-05-31
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