Increased Systemic Antioxidant Power Ameliorates the Aging-Related Reduction in Oocyte Competence in Mice

Int J Mol Sci. 2021 Dec 1;22(23):13019. doi: 10.3390/ijms222313019.

Abstract

Ovarian aging is associated with elevated oxidative stress and diminished oocyte developmental competence. We aimed to determine the impact of systemic antioxidant treatment in aged mice. Female outbred CF-1 mice were aged for 9 months prior to an 8-week 45 mg Euterpe oleracea (açaí) daily supplement. The açaí treatment induced a threefold increase in serum antioxidant power (FRAP) compared to both young and aged mice (p < 0.0001). Compared to young mice, aged mice had fewer oocytes and reduced blastocyst development (p < 0.0001); açaí did not affect the oocyte numbers, but improved blastocyst formation (p < 0.05). Additionally, açaí alleviated the aging-related decrease in implantation potential (p < 0.01). The aged mice showed evidence of elevated ovarian ER stress (increased whole-ovary PDIA4 expression, granulosa cell and oocyte GRP78 expression, and oocyte PDIA4 protein), reduced oocyte mitochondrial quality (higher PRKN activation and mitochondrial DNA oxidative damage), and dysregulated uterine glandular epithelium. Antioxidant intervention was sufficient to lessen these effects of ovarian aging, likely in part by the upregulation of NRF2. We conclude that açaí treatment is a promising strategy to improve ER and mitochondrial function in the ovaries, thereby ameliorating the decreased oocyte competence that occurs with ovarian aging.

Keywords: aging; antioxidants; infertility; oocyte competence; oxidative stress.

MeSH terms

  • Aging*
  • Animals
  • Antioxidants / chemistry
  • Antioxidants / metabolism*
  • Blastocyst / cytology
  • Blastocyst / drug effects
  • Blastocyst / metabolism
  • Endoplasmic Reticulum Chaperone BiP / genetics
  • Endoplasmic Reticulum Chaperone BiP / metabolism
  • Endoplasmic Reticulum Stress / drug effects
  • Endoplasmic Reticulum Stress / genetics
  • Euterpe / chemistry
  • Euterpe / metabolism
  • Female
  • Mice
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Oocytes / cytology
  • Oocytes / drug effects
  • Oocytes / metabolism*
  • Oxidative Stress / drug effects
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • Protein Disulfide-Isomerases / genetics
  • Protein Disulfide-Isomerases / metabolism
  • Superoxide Dismutase-1 / genetics
  • Superoxide Dismutase-1 / metabolism

Substances

  • Antioxidants
  • Endoplasmic Reticulum Chaperone BiP
  • Hspa5 protein, mouse
  • Plant Extracts
  • Superoxide Dismutase-1
  • Pdia4 protein, mouse
  • Protein Disulfide-Isomerases