Zhu Zhenye, Lei Min, Guo Ruizhi, Xu Yining, Zhao Yanqing, Wei Chenlu, Yang Qingling, Sun Yingpu
Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
J Ovarian Res. 2025 Jan 20;18(1):9. doi: 10.1186/s13048-025-01596-4.
Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility among women of reproductive age, yet the range of effective treatment options remains limited. Our previous study revealed that reduced levels of nicotinamide adenine dinucleotide (NAD) in ovarian granulosa cells (GCs) of women with PCOS resulted in the accumulation of reactive oxygen species (ROS) and mitochondrial dysfunction. However, it is still uncertain whether increasing NAD levels in the ovaries could improve ovarian function in PCOS. In this study, we demonstrated that supplementation with the NAD precursor nicotinamide riboside (NR) prevented the decrease in ovarian NAD levels, normalized estrous cycle irregularities, and enhanced ovulation potential in dehydroepiandrosterone (DHEA)-induced PCOS mice. Moreover, NR supplementation alleviated ovarian fibrosis and enhanced mitochondrial function in ovarian stromal cells of PCOS mice. Furthermore, NR supplementation improved oocyte quality in PCOS mice, as evidenced by reduced abnormal mitochondrial clustering, enhanced mitochondrial membrane potential, decreased ROS levels, reduced spindle abnormality rates, and increased early embryonic development potential in fertilized oocytes. These findings suggest that supplementing with NAD precursors could be a promising therapeutic strategy for addressing ovarian infertility associated with PCOS.
多囊卵巢综合征（PCOS）是育龄女性无排卵性不孕的主要原因，然而有效的治疗选择范围仍然有限。我们之前的研究表明，PCOS女性卵巢颗粒细胞（GCs）中烟酰胺腺嘌呤二核苷酸（NAD）水平降低导致活性氧（ROS）积累和线粒体功能障碍。然而，卵巢中NAD水平升高是否能改善PCOS患者的卵巢功能仍不确定。在本研究中，我们证明补充NAD前体烟酰胺核糖（NR）可防止卵巢NAD水平降低，使发情周期不规则恢复正常，并增强脱氢表雄酮（DHEA）诱导的PCOS小鼠的排卵潜能。此外，补充NR可减轻PCOS小鼠卵巢纤维化并增强卵巢基质细胞的线粒体功能。此外，补充NR可改善PCOS小鼠的卵母细胞质量，表现为异常线粒体聚集减少、线粒体膜电位增强、ROS水平降低、纺锤体异常率降低以及受精卵早期胚胎发育潜能增加。这些发现表明，补充NAD前体可能是解决与PCOS相关的卵巢性不孕的一种有前景的治疗策略。
