hUMSC transplantation restores follicle development in ovary damaged mice via re-establish extracellular matrix (ECM) components
Abstract Objectives Explore the therapeutic role of human umbilical mesenchymal stem cells (hUMSCs) transplantation for regeneration of ECM components and restoration of follicular development in mice. Background The extracellular matrix (ECM) is crucial to maintain ovary function and regulate folli...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-08-01
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| Series: | Journal of Ovarian Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13048-023-01217-y |
| _version_ | 1797557191431946240 |
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| author | Yin Shuyuan Wang Meimei Li Fenghua Zhao Huishan Chu Min Bao Hongchu Liu Xuemei |
| author_facet | Yin Shuyuan Wang Meimei Li Fenghua Zhao Huishan Chu Min Bao Hongchu Liu Xuemei |
| author_sort | Yin Shuyuan |
| collection | DOAJ |
| description | Abstract Objectives Explore the therapeutic role of human umbilical mesenchymal stem cells (hUMSCs) transplantation for regeneration of ECM components and restoration of follicular development in mice. Background The extracellular matrix (ECM) is crucial to maintain ovary function and regulate follicular development, as it participates in important cell signaling and provides physical support to the cells. However, it is unknown how hUMSCs affect the expression of ECM-related genes in ovaries treated with cyclophosphamide (CTX) and busulfan (BUS). Methods In the present study, we used 64 six- to eight-week-old ICR female mice to established mouse model. The mice were randomly divided into four groups (n = 16/group): control, POI, POI + hUMSCs, and POI + PBS group. The premature ovarian insufficiency (POI) mouse model was established by intraperitoneal injection of CTX and BUS for 7days, then, hUMSCs or PBS were respectively injected via the tail vein in POI + hUMSCs or POI + PBS group. Another 7days after injection, the mice were sacrificed to harvest the ovary tissue. The ovaries were immediately frozen with liquid nitrogen or fixed with 4% PFA for subsequent experiments. To screen differentially expressed genes (DEGs), we performed transcriptome sequencing of ovaries. Thereafter, a Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to predict the related biological functions. Retrieval of interacting genes for ECM-related DEGs was performed using the function of STRINGdb (version 2.6.5) to evaluate potential protein-protein interaction (PPI) networks. Furthermore, qRT-PCR and IHC were performed to assess the differential expression of selected DEGs in control, damaged, hUMSCs-transplanted and non-transplanted ovaries. Results Chemotherapy caused mouse ovarian follicular reserve depletion, and hUMSCs transplantation partially restored follicular development. Our results revealed that ECM-receptor interaction and ECM organization were both downregulated in the damaged ovaries. Further investigation showed that ECM-related genes were downregulated in the CTX and BUS treatment group and partially rescued in hUMSCs injection group but not in the PBS group. qRT-PCR and IHC verified the results: collagen IV and laminin gamma 3 were both expressed around follicle regions in normal ovaries, chemotherapy treatment disrupted their expression, and hUMSCs transplantation rescued their localization and expression to some extent. Conclusion Our data demonstrated that ECM-related genes participate in the regulation of ovarian reserve, hUMSCs treatment rescued abnormal expression and localization of collagen IV and laminin gamma 3 in the damaged ovaries. The results suggest that hUMSCs transplantation can maintain ECM-stable microenvironments, which is beneficial to follicular development. |
| first_indexed | 2024-03-10T17:13:52Z |
| format | Article |
| id | doaj.art-2191121d0e6e4496922a4024326a5129 |
| institution | Directory Open Access Journal |
| issn | 1757-2215 |
| language | English |
| last_indexed | 2024-03-10T17:13:52Z |
| publishDate | 2023-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Ovarian Research |
| spelling | doaj.art-2191121d0e6e4496922a4024326a51292023-11-20T10:32:37ZengBMCJournal of Ovarian Research1757-22152023-08-0116111210.1186/s13048-023-01217-yhUMSC transplantation restores follicle development in ovary damaged mice via re-establish extracellular matrix (ECM) componentsYin Shuyuan0Wang Meimei1Li Fenghua2Zhao Huishan3Chu Min4Bao Hongchu5Liu Xuemei6Reproductive Medicine Centre, The Affiliated Yantai Yuhuangding Hospital of Qingdao UniversityReproductive Medicine Centre, The Affiliated Yantai Yuhuangding Hospital of Qingdao UniversityReproductive Medicine Centre, The Affiliated Yantai Yuhuangding Hospital of Qingdao UniversityReproductive Medicine Centre, The Affiliated Yantai Yuhuangding Hospital of Qingdao UniversityReproductive Medicine Centre, The Affiliated Yantai Yuhuangding Hospital of Qingdao UniversityReproductive Medicine Centre, The Affiliated Yantai Yuhuangding Hospital of Qingdao UniversityReproductive Medicine Centre, The Affiliated Yantai Yuhuangding Hospital of Qingdao UniversityAbstract Objectives Explore the therapeutic role of human umbilical mesenchymal stem cells (hUMSCs) transplantation for regeneration of ECM components and restoration of follicular development in mice. Background The extracellular matrix (ECM) is crucial to maintain ovary function and regulate follicular development, as it participates in important cell signaling and provides physical support to the cells. However, it is unknown how hUMSCs affect the expression of ECM-related genes in ovaries treated with cyclophosphamide (CTX) and busulfan (BUS). Methods In the present study, we used 64 six- to eight-week-old ICR female mice to established mouse model. The mice were randomly divided into four groups (n = 16/group): control, POI, POI + hUMSCs, and POI + PBS group. The premature ovarian insufficiency (POI) mouse model was established by intraperitoneal injection of CTX and BUS for 7days, then, hUMSCs or PBS were respectively injected via the tail vein in POI + hUMSCs or POI + PBS group. Another 7days after injection, the mice were sacrificed to harvest the ovary tissue. The ovaries were immediately frozen with liquid nitrogen or fixed with 4% PFA for subsequent experiments. To screen differentially expressed genes (DEGs), we performed transcriptome sequencing of ovaries. Thereafter, a Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to predict the related biological functions. Retrieval of interacting genes for ECM-related DEGs was performed using the function of STRINGdb (version 2.6.5) to evaluate potential protein-protein interaction (PPI) networks. Furthermore, qRT-PCR and IHC were performed to assess the differential expression of selected DEGs in control, damaged, hUMSCs-transplanted and non-transplanted ovaries. Results Chemotherapy caused mouse ovarian follicular reserve depletion, and hUMSCs transplantation partially restored follicular development. Our results revealed that ECM-receptor interaction and ECM organization were both downregulated in the damaged ovaries. Further investigation showed that ECM-related genes were downregulated in the CTX and BUS treatment group and partially rescued in hUMSCs injection group but not in the PBS group. qRT-PCR and IHC verified the results: collagen IV and laminin gamma 3 were both expressed around follicle regions in normal ovaries, chemotherapy treatment disrupted their expression, and hUMSCs transplantation rescued their localization and expression to some extent. Conclusion Our data demonstrated that ECM-related genes participate in the regulation of ovarian reserve, hUMSCs treatment rescued abnormal expression and localization of collagen IV and laminin gamma 3 in the damaged ovaries. The results suggest that hUMSCs transplantation can maintain ECM-stable microenvironments, which is beneficial to follicular development.https://doi.org/10.1186/s13048-023-01217-yFollicular DevelopmentOvarian ReserveTranscriptome sequencingExtracellular matrixMesenchymal stem cells |
| spellingShingle | Yin Shuyuan Wang Meimei Li Fenghua Zhao Huishan Chu Min Bao Hongchu Liu Xuemei hUMSC transplantation restores follicle development in ovary damaged mice via re-establish extracellular matrix (ECM) components Journal of Ovarian Research Follicular Development Ovarian Reserve Transcriptome sequencing Extracellular matrix Mesenchymal stem cells |
| title | hUMSC transplantation restores follicle development in ovary damaged mice via re-establish extracellular matrix (ECM) components |
| title_full | hUMSC transplantation restores follicle development in ovary damaged mice via re-establish extracellular matrix (ECM) components |
| title_fullStr | hUMSC transplantation restores follicle development in ovary damaged mice via re-establish extracellular matrix (ECM) components |
| title_full_unstemmed | hUMSC transplantation restores follicle development in ovary damaged mice via re-establish extracellular matrix (ECM) components |
| title_short | hUMSC transplantation restores follicle development in ovary damaged mice via re-establish extracellular matrix (ECM) components |
| title_sort | humsc transplantation restores follicle development in ovary damaged mice via re establish extracellular matrix ecm components |
| topic | Follicular Development Ovarian Reserve Transcriptome sequencing Extracellular matrix Mesenchymal stem cells |
| url | https://doi.org/10.1186/s13048-023-01217-y |
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