Intravenous human endothelial progenitor cell administration into aged mice enhances embryo development and oocyte quality by reducing inflammation, endoplasmic reticulum stress and apoptosis

J Vet Med Sci. 2018 Dec 26;80(12):1905-1913. doi: 10.1292/jvms.18-0242. Epub 2018 Oct 29.

Abstract

Stem cell therapy has been proposed to restore the function and structure of injured tissues. In the present study, we investigated the ability of human endothelial progenitor cells (hEPCs) to attenuate ovarian aging and dysfunction. Female ICR mice aged 4 and 6 months were injected with cultured hEPCs. Cultured hEPCs were injected intravenously twice with 5 × 104 cells with a 4 day interval. After pregnant mare serum gonadotropin and human chorionic gonadotropin stimulation, oocytes and ovaries of aged mice were collected, cumulus-free oocytes were activated by SrCl2 and gene expression levels related to inflammation, apoptosis, follicle development and endoplasmic reticulum (ER) stress in ovaries were compared. Administration of hEPCs attenuated the level of inflammatory cytokines and adverse apoptotic factor, as well as reducing ER stress in the ovaries. Increased cleavage and blastocyst formation rates and cell numbers in blastocysts from hEPCs-treated aged mice vs. same aged control mice demonstrated a protective function of hEPCs against reproductive aging. Based on these data, we suggest that treatment with hEPCs attenuates reproductive aging and dysfunction potentially via regulation of inflammation, apoptosis and ER stress.

Keywords: endoplasmic reticulum stress; human endothelial progenitor cells; inflammation; ovarian aging.

MeSH terms

  • Aging* / genetics
  • Animals
  • Apoptosis*
  • Cells, Cultured
  • Cytokines / genetics
  • Cytokines / metabolism
  • Embryonic Development*
  • Endoplasmic Reticulum Stress*
  • Endothelial Progenitor Cells / transplantation*
  • Female
  • Fertility
  • Gene Expression
  • Humans
  • Inflammation / prevention & control*
  • Inflammation Mediators / metabolism
  • Mice
  • Mice, Inbred ICR
  • Ovarian Follicle / growth & development
  • Ovary / metabolism
  • Ovary / physiology*
  • Parthenogenesis
  • Transplantation, Heterologous

Substances

  • Cytokines
  • Inflammation Mediators