Increasing ovarian NAD + levels improve mitochondrial functions and reverse ovarian aging

Free Radic Biol Med. 2020 Aug 20;156:1-10. doi: 10.1016/j.freeradbiomed.2020.05.003. Epub 2020 May 31.

Abstract

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.

Keywords: Infertility; Mitochondria; NAD(+); Ovary aging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging
  • Animals
  • Energy Metabolism
  • Female
  • Mice
  • Mitochondria* / metabolism
  • NAD* / metabolism
  • Niacinamide / metabolism
  • Reactive Oxygen Species / metabolism

Substances

  • Reactive Oxygen Species
  • NAD
  • Niacinamide