BDNF secreted by mesenchymal stem cells improves aged oocyte quality and development potential by activating the

Jing Zhou1,2,3,4,5,6,7,8, Cheng Li1,2,3,4,5,6,7, Xin Mi1,2,3,4,5,6,7

  • 1State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, Shandong, 250012, China.

Abstract

Insights

Mesenchymal stem cell secretome improves oocyte quality in aged mice and humans. Brain-derived neurotrophic factor (BDNF) is the key component, enhancing oocyte development via ERK1/2 pathway activation.

Area of Science:

  • Reproductive biology
  • Stem cell research
  • Molecular mechanisms of aging

Background:

  • Age-related decline in oocyte quality significantly impacts fertility.
  • Current treatments for reduced oocyte quality are limited.
  • Mesenchymal stem cell secretome (MSC-sec) shows potential for improving oocyte quality.

Purpose of the Study:

  • Identify the active component within MSC-sec responsible for improving oocyte quality.
  • Elucidate the molecular mechanisms by which MSC-sec enhances oocyte quality in aged individuals.
  • Investigate the efficacy of MSC-sec and its components in both mouse and human oocytes.

Main Methods:

  • Immunofluorescence and chromosome spread analysis on aged mouse oocytes.
  • In vitro and in vivo experiments using BDNF and its neutralization antibody.
  • RNA-sequencing to analyze maternal mRNA degradation.
  • In vitro culture of aged human oocytes.

Main Results:

  • MSC-sec treatment improved spindle assembly and reduced aneuploidy in aged mouse oocytes.
  • BDNF was identified as the key component in MSC-sec that enhances oocyte quality.
  • BDNF activated the ERK1/2 signaling pathway, increasing DAZL and BTG4 expression.
  • BDNF treatment improved fertilization and blastocyst formation rates in aged human oocytes.

Conclusions:

  • BDNF secreted by MSCs effectively improves oocyte quality and developmental potential in aged mice and humans.
  • The ERK1/2 signaling pathway is crucial for BDNF-mediated oocyte quality enhancement.
  • BDNF presents a promising therapeutic strategy to counteract age-related oocyte quality decline.

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