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Nampt affects mitochondrial function in aged oocytes by mediating the downstream effector FoxO3a.

Qingrui Zhuan1, Jun Li2, Xingzhu Du1

  • 1National Engineering Laboratory for Animal Breeding, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China.

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|July 28, 2021
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Summary

Maternal aging impairs oocyte quality, increasing reactive oxygen species and altering protein levels like FoxO3a. Suppressing Nampt further damages mitochondrial function in aged oocytes.

Keywords:
FoxO3aNamptmaternal-agingmitochondriaoocyte

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Area of Science:

  • Reproductive Biology
  • Cellular Aging
  • Mitochondrial Biology

Background:

  • Maternal aging negatively impacts oocyte quality and developmental potential.
  • Oocyte aging is associated with cellular stress, including increased reactive oxygen species (ROS).

Purpose of the Study:

  • To investigate the effects of maternal aging on oocyte quality and mitochondrial function in mice.
  • To explore the roles of Forkhead box O3a (FoxO3a) and nicotinamide-phosphoribosyltransferase (Nampt) in aged oocytes.

Main Methods:

  • Comparative analysis of oocytes from young and aged mice.
  • Measurement of reactive oxygen species (ROS), mitochondrial calcium (Ca2+), and temperature.
  • Assessment of FoxO3a and Nampt expression and localization.
  • Pharmacological manipulation of Nampt activity using P7C3 and FK866.

Main Results:

  • Aged oocytes exhibited compromised germinal vesicle breakdown (GVBD), elevated ROS, and altered mitochondrial Ca2+ and temperature.
  • FoxO3a expression and nuclear localization increased in aged oocytes.
  • Nampt expression was upregulated in aged oocytes and ovaries, peaking during GVBD.
  • FK866 treatment significantly reduced ATP levels and mitochondrial membrane potential in aged oocytes.

Conclusions:

  • Mitochondrial dysfunction in aged oocytes is linked to elevated FoxO3a levels.
  • Suppression of Nampt exacerbates mitochondrial dysfunction in aged oocytes, highlighting its critical role.