Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Henan Provincial Obstetrical and Gynecological Diseases (Reproductive Medicine) Clinical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Henan Engineering Laboratory of Preimplantation Genetic Diagnosis and Screening, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Henan Provincial Obstetrical and Gynecological Diseases (Reproductive Medicine) Clinical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Henan Engineering Laboratory of Preimplantation Genetic Diagnosis and Screening, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Free Radic Biol Med. 2020 Aug 20;156:1-10. doi: 10.1016/j.freeradbiomed.2020.05.003. Epub 2020 May 31.
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.
卵泡的损耗以及卵母细胞质量和数量的减少导致与年龄相关的卵巢衰老和不孕。尽管卵巢衰老的潜在机制尚不清楚，但已经报道了线粒体功能障碍。在这里，我们显示了小鼠卵巢烟酰胺腺嘌呤二核苷酸（NAD）水平随年龄的依赖性下降，而补充衰老小鼠烟酰胺核糖（NR），一种 NAD 前体，增加了卵巢 NAD 含量。我们发现，衰老小鼠卵巢 NAD 水平的增加导致了卵巢卵泡数量和排卵能力的增加，以及活产率的增加。NR 补充还降低了衰老卵母细胞中的活性氧水平和纺锤体异常，同时增加了线粒体膜电位（ΔΨm）和减少了线粒体聚集。此外，NR 补充改善了卵巢线粒体能量代谢。我们的数据表明，体内和体外补充 NAD 前体可能是治疗与年龄相关的卵巢不孕的潜在治疗方法。
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