Placental mesenchymal stem cells ameliorate NLRP3 inflammasome-induced ovarian insufficiency by modulating macrophage M2 polarization
Abstract Background Premature ovarian insufficiency (POI) is a common clinical problem, however, there are currently no effective therapies. Pyroptosis induced by the NLRP3 inflammasome is considered a possible mechanism of POI. Placental mesenchymal stem cells (PMSCs) have excellent immunomodulator...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | Journal of Ovarian Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13048-023-01136-y |
| _version_ | 1797863904351617024 |
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| author | Dongmei Chen Na Hu Shasha Xing Li Yang Feiyan Zhang Songlin Guo Shudan Liu Xiaona Ma Xueyun Liang Huiming Ma |
| author_facet | Dongmei Chen Na Hu Shasha Xing Li Yang Feiyan Zhang Songlin Guo Shudan Liu Xiaona Ma Xueyun Liang Huiming Ma |
| author_sort | Dongmei Chen |
| collection | DOAJ |
| description | Abstract Background Premature ovarian insufficiency (POI) is a common clinical problem, however, there are currently no effective therapies. Pyroptosis induced by the NLRP3 inflammasome is considered a possible mechanism of POI. Placental mesenchymal stem cells (PMSCs) have excellent immunomodulatory potential and offer a promising method for treating POI. Methods Female Sprague–Dawley rats were randomly divided into four treatment groups: control (no POI), POI with no PMSCs, POI with PMSCs transplant, and POI with hormones (estrogen + progesterone) as positive control. POI was induced by exposure to 4-vinylcyclohexene diepoxide (VCD) for 15 days. After four weeks, all animals were euthanized and examined for pathology. Hormone levels were measured and ovarian function was evaluated in relation to the estrous cycle. Levels of NLRP3 inflammasome pathway proteins were determined by immunohistochemistry and western blot. Results VCD significantly damaged rat follicles at different estrous stages. Injection of human PMSCs improved ovarian function and reproductive ability of POI rats compared to the sham and hormone groups. Our data also showed that PMSCs markedly suppress cell pyroptosis via downregulation of the NLRP3 inflammasome, caspase-1, IL-1β and IL-18 compared to the other two groups. The human PMSCs increased the expression of IL-4 and IL-10 and decreased pro-inflammatory factors by phenotypic changes in macrophages. Conclusions Our findings revealed a novel mechanism of follicular dysfunction and ovarian fibrosis via activation of the NLRP3 inflammasome followed by secretion of pro-inflammatory factors. Transplantation of PMSCs into POI rats suppressed pro-inflammatory factor production, NLRP3 inflammasome formation and pyroptosis, and improved ovarian function. |
| first_indexed | 2024-04-09T22:43:03Z |
| format | Article |
| id | doaj.art-d4c044bbffd84232acae117fad316864 |
| institution | Directory Open Access Journal |
| issn | 1757-2215 |
| language | English |
| last_indexed | 2024-04-09T22:43:03Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Ovarian Research |
| spelling | doaj.art-d4c044bbffd84232acae117fad3168642023-03-22T12:03:51ZengBMCJournal of Ovarian Research1757-22152023-03-0116111610.1186/s13048-023-01136-yPlacental mesenchymal stem cells ameliorate NLRP3 inflammasome-induced ovarian insufficiency by modulating macrophage M2 polarizationDongmei Chen0Na Hu1Shasha Xing2Li Yang3Feiyan Zhang4Songlin Guo5Shudan Liu6Xiaona Ma7Xueyun Liang8Huiming Ma9Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Sciences, General Hospital of Ningxia Medical UniversityKey Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical UniversityKey Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical UniversityLaboratory Animal Center, Ningxia Medical UniversityKey Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Sciences, General Hospital of Ningxia Medical UniversityKey Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Sciences, General Hospital of Ningxia Medical UniversityKey Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Sciences, General Hospital of Ningxia Medical UniversityKey Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Sciences, General Hospital of Ningxia Medical UniversityKey Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Sciences, General Hospital of Ningxia Medical UniversityKey Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical UniversityAbstract Background Premature ovarian insufficiency (POI) is a common clinical problem, however, there are currently no effective therapies. Pyroptosis induced by the NLRP3 inflammasome is considered a possible mechanism of POI. Placental mesenchymal stem cells (PMSCs) have excellent immunomodulatory potential and offer a promising method for treating POI. Methods Female Sprague–Dawley rats were randomly divided into four treatment groups: control (no POI), POI with no PMSCs, POI with PMSCs transplant, and POI with hormones (estrogen + progesterone) as positive control. POI was induced by exposure to 4-vinylcyclohexene diepoxide (VCD) for 15 days. After four weeks, all animals were euthanized and examined for pathology. Hormone levels were measured and ovarian function was evaluated in relation to the estrous cycle. Levels of NLRP3 inflammasome pathway proteins were determined by immunohistochemistry and western blot. Results VCD significantly damaged rat follicles at different estrous stages. Injection of human PMSCs improved ovarian function and reproductive ability of POI rats compared to the sham and hormone groups. Our data also showed that PMSCs markedly suppress cell pyroptosis via downregulation of the NLRP3 inflammasome, caspase-1, IL-1β and IL-18 compared to the other two groups. The human PMSCs increased the expression of IL-4 and IL-10 and decreased pro-inflammatory factors by phenotypic changes in macrophages. Conclusions Our findings revealed a novel mechanism of follicular dysfunction and ovarian fibrosis via activation of the NLRP3 inflammasome followed by secretion of pro-inflammatory factors. Transplantation of PMSCs into POI rats suppressed pro-inflammatory factor production, NLRP3 inflammasome formation and pyroptosis, and improved ovarian function.https://doi.org/10.1186/s13048-023-01136-yPlacental mesenchymal stem cellsPremature ovarian insufficiencyMacrophageInflammasomeNLRP3Interferon-γ |
| spellingShingle | Dongmei Chen Na Hu Shasha Xing Li Yang Feiyan Zhang Songlin Guo Shudan Liu Xiaona Ma Xueyun Liang Huiming Ma Placental mesenchymal stem cells ameliorate NLRP3 inflammasome-induced ovarian insufficiency by modulating macrophage M2 polarization Journal of Ovarian Research Placental mesenchymal stem cells Premature ovarian insufficiency Macrophage Inflammasome NLRP3 Interferon-γ |
| title | Placental mesenchymal stem cells ameliorate NLRP3 inflammasome-induced ovarian insufficiency by modulating macrophage M2 polarization |
| title_full | Placental mesenchymal stem cells ameliorate NLRP3 inflammasome-induced ovarian insufficiency by modulating macrophage M2 polarization |
| title_fullStr | Placental mesenchymal stem cells ameliorate NLRP3 inflammasome-induced ovarian insufficiency by modulating macrophage M2 polarization |
| title_full_unstemmed | Placental mesenchymal stem cells ameliorate NLRP3 inflammasome-induced ovarian insufficiency by modulating macrophage M2 polarization |
| title_short | Placental mesenchymal stem cells ameliorate NLRP3 inflammasome-induced ovarian insufficiency by modulating macrophage M2 polarization |
| title_sort | placental mesenchymal stem cells ameliorate nlrp3 inflammasome induced ovarian insufficiency by modulating macrophage m2 polarization |
| topic | Placental mesenchymal stem cells Premature ovarian insufficiency Macrophage Inflammasome NLRP3 Interferon-γ |
| url | https://doi.org/10.1186/s13048-023-01136-y |
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