Nicotinamide Mononucleotide Supplementation Reverses the Declining Quality of Maternally Aged Oocytes

Cell Rep. 2020 Aug 4;32(5):107987. doi: 10.1016/j.celrep.2020.107987.


Advanced maternal age is highly associated with a decline in oocyte quality, but effective approaches to improve it have still not been fully determined. Here, we report that in vivo supplementation of nicotinamide mononucleotide (NMN) efficaciously improves the quality of oocytes from naturally aged mice by recovering nicotinamide adenine dinucleotide (NAD+) levels. NMN supplementation not only increases ovulation of aged oocytes but also enhances their meiotic competency and fertilization ability by maintaining the normal spindle/chromosome structure and the dynamics of the cortical granule component ovastacin. Moreover, single-cell transcriptome analysis shows that the beneficial effect of NMN on aged oocytes is mediated by restoration of mitochondrial function, eliminating the accumulated ROS to suppress apoptosis. Collectively, our data reveal that NMN supplementation is a feasible approach to protect oocytes from advanced maternal age-related deterioration, contributing to the improvement of reproductive outcome of aged women and assisted reproductive technology.

Keywords: NAD; NMN; maternal age; mitochondrial function; oocyte quality.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Animals
  • Apoptosis / drug effects
  • Cellular Senescence* / drug effects
  • Chromosomes, Mammalian / metabolism
  • Cytoplasmic Granules / drug effects
  • Cytoplasmic Granules / metabolism
  • DNA Damage
  • Dietary Supplements
  • Embryonic Development / drug effects
  • Embryonic Development / genetics
  • Female
  • Fertilization / drug effects
  • Kinetochores / drug effects
  • Kinetochores / metabolism
  • Male
  • Meiosis / drug effects
  • Metalloproteases / metabolism
  • Mice, Inbred ICR
  • Microtubules / drug effects
  • Microtubules / metabolism
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • NAD / metabolism
  • Nicotinamide Mononucleotide / pharmacology*
  • Oocytes / cytology*
  • Oocytes / drug effects
  • Reactive Oxygen Species / metabolism
  • Spermatozoa / drug effects
  • Spermatozoa / metabolism
  • Spindle Apparatus / drug effects
  • Spindle Apparatus / metabolism
  • Transcriptome / genetics


  • Reactive Oxygen Species
  • NAD
  • Nicotinamide Mononucleotide
  • Astl protein, mouse
  • Metalloproteases