Human Amniotic Fluid Mesenchymal Stem Cell-Derived Exosomes Inhibit Apoptosis in Ovarian Granulosa Cell via miR-369-3p/YAF2/PDCD5/p53 Pathway

Zixiang Geng; Haiyang Chen; Gang Zou; Long Yuan; Peng Liu; Bingrong Li; Kaiyong Zhang; Fangyuan Jing; Xiaoli Nie; Te Liu; Bimeng Zhang

doi:10.1155/2022/3695848

Human Amniotic Fluid Mesenchymal Stem Cell-Derived Exosomes Inhibit Apoptosis in Ovarian Granulosa Cell via miR-369-3p/YAF2/PDCD5/p53 Pathway

Oxid Med Cell Longev. 2022 Jul 26:2022:3695848. doi: 10.1155/2022/3695848. eCollection 2022.

Authors

Zixiang Geng^{1

2}, Haiyang Chen³, Gang Zou⁴, Long Yuan¹, Peng Liu¹, Bingrong Li¹, Kaiyong Zhang¹, Fangyuan Jing³, Xiaoli Nie³, Te Liu³, Bimeng Zhang¹

Affiliations

¹ Department of Acupuncture and Moxibustion, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200086, China.
² Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
³ Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, China.
⁴ Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, China.

Abstract

Human amniotic fluid stem cell-derived exosome (HuAFSC-exosome) transplantation is considered a promising treatment for premature ovarian failure (POF). However, its mechanism remains unclear. In this study, exosomes were isolated and enriched from HuAFSC subsets of CD44+/CD105+, and the exosomes were transplanted into a POF model in vitro and in vivo. Our results confirmed that the exosomes produced by CD44+/CD105+ HuAFSCs could achieve therapeutic effects in a mouse POF model. Our research also showed that CD44+/CD105+ HuAFSC-exosomes carrying miR-369-3p could specifically downregulate the expression of YAF2, inhibit the stability of PDCD5/p53, and reduce the apoptosis of ovarian granulosa cells (OGCs), thereby exerting therapeutic effects on POF. Knowledge of these mechanisms demonstrates that miRNAs carried by CD44+/CD105+ HuAFSC-exosomes are critical to the therapy of POF. This will be useful for the clinical application of stem cells.

MeSH terms

Amniotic Fluid / metabolism
Animals
Apoptosis
Apoptosis Regulatory Proteins / metabolism
Disease Models, Animal
Exosomes* / metabolism
Female
Granulosa Cells / metabolism
Humans
Mesenchymal Stem Cells* / metabolism
Mice
MicroRNAs* / genetics
MicroRNAs* / metabolism
Muscle Proteins / metabolism
Neoplasm Proteins / metabolism
Primary Ovarian Insufficiency* / genetics
Primary Ovarian Insufficiency* / therapy
Repressor Proteins / metabolism
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / metabolism

Substances

Apoptosis Regulatory Proteins
MIRN369 microRNA, human
MicroRNAs
Muscle Proteins
Neoplasm Proteins
PDCD5 protein, human
Pdcd5 protein, mouse
Repressor Proteins
Tumor Suppressor Protein p53
YAF2 protein, human
Yaf2 protein, mouse