Affiliation:
1. Center for Reproductive Medicine The First Affiliated Hospital of Zhengzhou University Zhengzhou China
2. Henan Key Laboratory of Reproduction and Genetics The First Affiliated Hospital of Zhengzhou University Zhengzhou China
3. Henan Provincial Obstetrical and Gynecological Diseases (Reproductive Medicine) Clinical Research Center The First Affiliated Hospital of Zhengzhou University Zhengzhou China
Abstract
AbstractRecent advances highlight the pivotal role of nicotinamide adenine dinucleotide (NAD+) in ovarian aging. However, the roles of de novo NAD+ biosynthesis on ovarian aging are still unknown. Here, we found that genetic ablation of Ido1 (indoleamine‐2,3‐dioxygenase 1) or Qprt (Quinolinate phosphoribosyl transferase), two critical genes in de novo NAD+ biosynthesis, resulted in decreased ovarian NAD+ levels in middle‐aged mice, leading to subfertility, irregular estrous cycles, reduced ovarian reserve, and accelerated aging. Moreover, we observed impaired oocyte quality, characterized by increased reactive oxygen species and spindle anomalies, which ultimately led to reduced fertilization ability and impaired early embryonic development. A transcriptomic analysis of ovaries in both mutant and wild‐type mice revealed alterations in gene expression related to mitochondrial metabolism. Our findings were further supported by the observation of impaired mitochondrial distribution and decreased mitochondrial membrane potential in the oocytes of knockout mice. Supplementation with nicotinamide riboside (NR), an NAD+ booster, in mutant mice increased ovarian reserve and improved oocyte quality. Our study highlights the importance of the NAD+ de novo pathway in middle‐aged female fertility.
Funder
National Natural Science Foundation of China
Cited by
2 articles.
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