hUMSC transplantation restores ovarian function in POI rats by inhibiting autophagy of theca-interstitial cells via the AMPK/mTOR signaling pathway.

AMP-Activated Protein Kinases / genetics Animals Autophagy Female Humans Mesenchymal Stem Cell Transplantation Primary Ovarian Insufficiency / chemically induced Rats Signal Transduction TOR Serine-Threonine Kinases / genetics
AMPK Autophagy Human umbilical cord-derived mesenchymal stem cells Oxidative stress Primary ovarian insufficiency Theca-interstitial cells

Journal

Stem cell research & therapy
ISSN: 1757-6512
Titre abrégé: Stem Cell Res Ther
Pays: England
ID NLM: 101527581

Informations de publication

Date de publication:
03 07 2020
Historique:
received: 08 12 2019
accepted: 18 06 2020
revised: 05 05 2020
entrez: 5 7 2020
pubmed: 6 7 2020
medline: 22 6 2021
Statut: epublish

Résumé

Previous studies of primary ovarian insufficiency (POI) have focused on granulosa cells (GCs) and ignored the role of theca-interstitial cells (TICs). This study aims to explore the mechanism of the protective effects of human umbilical cord-derived mesenchymal stem cells (hUMSCs) on ovarian function in POI rats by regulating autophagy of TICs. The POI model was established in rats treated with cisplatin (CDDP). The hUMSCs were transplanted into POI rats by tail vein. Enzyme-linked immunosorbent assay (ELISA) analysis, hematoxylin and eosin (HE) staining, and immunohistochemistry were used to measure the protective effects of hUMSCs. The molecular mechanisms of injury and repairment of TICs were assessed by immunofluorescence, transmission electron microscope (TEM), flow cytometry (FCM), western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). In vivo, hUMSC transplantation restored the ovarian function and alleviated the apoptosis of TICs in POI rats. In vitro, hUMSCs reduced the autophagy levels of TICs by reducing oxidative stress and regulating AMPK/mTOR signaling pathway, thereby alleviating the apoptosis of TICs. This study indicates that hUMSCs protected ovarian function in POI by regulating autophagy signaling pathway AMPK/mTOR.

Sections du résumé

BACKGROUND
Previous studies of primary ovarian insufficiency (POI) have focused on granulosa cells (GCs) and ignored the role of theca-interstitial cells (TICs). This study aims to explore the mechanism of the protective effects of human umbilical cord-derived mesenchymal stem cells (hUMSCs) on ovarian function in POI rats by regulating autophagy of TICs.
METHODS
The POI model was established in rats treated with cisplatin (CDDP). The hUMSCs were transplanted into POI rats by tail vein. Enzyme-linked immunosorbent assay (ELISA) analysis, hematoxylin and eosin (HE) staining, and immunohistochemistry were used to measure the protective effects of hUMSCs. The molecular mechanisms of injury and repairment of TICs were assessed by immunofluorescence, transmission electron microscope (TEM), flow cytometry (FCM), western blot, and quantitative real-time polymerase chain reaction (qRT-PCR).
RESULTS
In vivo, hUMSC transplantation restored the ovarian function and alleviated the apoptosis of TICs in POI rats. In vitro, hUMSCs reduced the autophagy levels of TICs by reducing oxidative stress and regulating AMPK/mTOR signaling pathway, thereby alleviating the apoptosis of TICs.
CONCLUSION
This study indicates that hUMSCs protected ovarian function in POI by regulating autophagy signaling pathway AMPK/mTOR.

Identifiants

DOI: 10.1186/s13287-020-01784-7 PMID: 32620136 PMC: PMC7333437
pubmed: 32620136
doi: 10.1186/s13287-020-01784-7
pii: 10.1186/s13287-020-01784-7
pmc: PMC7333437
doi:

Substances chimiques

MTOR protein, human EC 2.7.1.1
mTOR protein, rat EC 2.7.1.1
TOR Serine-Threonine Kinases EC 2.7.11.1
AMP-Activated Protein Kinases EC 2.7.11.31

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

268

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Auteurs

Xueyan Lu (X)

College of Basic Medicine & Institute of Reproductive Diseases, Binzhou Medical University, Yantai, 264003, Shandong, China.
College of Basic Medicine, Binzhou Medical University, Yantai, 264003, Shandong, China.

Hongchu Bao (H)

Department of Clinical Medicine, Yantai Yuhuangding Hospital, Yantai, 264000, Shandong, China.

Linlu Cui (L)

College of Basic Medicine & Institute of Reproductive Diseases, Binzhou Medical University, Yantai, 264003, Shandong, China.
College of Basic Medicine, Binzhou Medical University, Yantai, 264003, Shandong, China.

Wenqian Zhu (W)

College of Basic Medicine & Institute of Reproductive Diseases, Binzhou Medical University, Yantai, 264003, Shandong, China.

Lianshuang Zhang (L)

College of Basic Medicine, Binzhou Medical University, Yantai, 264003, Shandong, China.

Zheng Xu (Z)

College of Basic Medicine, Binzhou Medical University, Yantai, 264003, Shandong, China.

Xuejing Man (X)

Department of Clinical Medicine, Yantai Yuhuangding Hospital, Yantai, 264000, Shandong, China.

Yongli Chu (Y)

Department of Clinical Medicine, Yantai Yuhuangding Hospital, Yantai, 264000, Shandong, China.

Qiang Fu (Q)

College of Basic Medicine, Binzhou Medical University, Yantai, 264003, Shandong, China. qiangfu11@fudan.edu.cn.

Hongqin Zhang (H)

College of Basic Medicine & Institute of Reproductive Diseases, Binzhou Medical University, Yantai, 264003, Shandong, China. byzhhq@bzmc.edu.cn.
College of Basic Medicine, Binzhou Medical University, Yantai, 264003, Shandong, China. byzhhq@bzmc.edu.cn.
ORCID: 0000-0003-1440-7365

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › AMP-Activated Protein Kinases › hUMSC transplantation restores ovarian...
questionsmedicales.fr › Eucaryotes › Animaux › hUMSC transplantation restores ovarian...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Autophagie › hUMSC transplantation restores ovarian...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › hUMSC transplantation restores ovarian...
questionsmedicales.fr › Procédures de chirurgie opératoire › Transplantation › Transplantation cellulaire › Transplantation de cellules souches › Transplantation de cellules souches mésenchymateuses › hUMSC transplantation restores ovarian...
questionsmedicales.fr › Maladies endocriniennes › Troubles gonadiques › Maladies ovariennes › Insuffisance ovarienne primitive › hUMSC transplantation restores ovarian...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › hUMSC transplantation restores ovarian...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › hUMSC transplantation restores ovarian...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Sérine-thréonine kinases TOR › hUMSC transplantation restores ovarian...