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Published on: January 8, 2017
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.
Background:
Reduced oocyte quality is a key factor in age-related fertility decline, and there are no effective treatments available. The secretome of mesenchymal stem cells (MSC-sec) contains various bioactive factors and has the potential to improve oocyte quality. This study aimed to investigate the effective component and molecular mechanism of MSC-sec involved in improving oocyte quality from aged mice and humans.
Methods:
Immunofluorescence and chromosome spread were performed to investigate the effects of secretome from human umbilical cord-MSC on spindle assembly and aneuploidy in aged mouse oocytes. Brain-derived neurotrophic factor (BDNF) and its neutralization antibody was supplemented in both in vitro and in vivo experiments to verify the effective component in MSC-sec. RNA-seq analysis was used to reveal the alterations in maternal mRNA degradation in aged mouse oocytes after MSC-sec treatment. In vitro culture of oocytes from aged women was also used to verify the effectiveness of BDNF in improving oocyte quality.
Results:
MSC-sec treatment significantly increased first polar body emission, improved spindle assembly, promoted maternal RNA degradation, and reduced aneuploidy rate in aged mouse oocytes. While the addition of BDNF neutralization antibody blocked the effects of MSC-sec, BDNF alone also increased the oocyte quality from aged mice. Mechanistically, both MSC-sec and BDNF rescued the quality of aged mouse oocytes by activating the ERK1/2 signaling pathway to increase the expression of DAZL and BTG4. In situ injection of MSC-sec or BDNF into aged mouse ovaries significantly improved oocyte quality and early embryonic development. Finally, we demonstrated that BDNF treatment increased both the fertilization rate and blastocyst formation rate of aged human oocytes.
Conclusion:
These findings demonstrate that BDNF secreted by mesenchymal stem cells can improve the quality and development potential of oocytes from both aged mice and humans by activating the ERK1/2 signaling pathway, suggesting that it has the potential to mitigate age-related declines in oocyte quality.
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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