Nicotinamide mononucleotide improves the ovarian reserve of POI by inhibiting NLRP3-mediated pyroptosis of ovarian granulosa cells
Abstract Background Premature ovarian insufficiency (POI) is a common clinical problem, but there is currently no effective treatment. NLRP3 inflammasome-induced pyroptosis is thought to be a possible mechanism of POI. Nicotinamide mononucleotide (NMN) has a certain anti-inflammatory effect, providi...
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| Language: | English |
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BMC
2024-11-01
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| Series: | Journal of Ovarian Research |
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| Online Access: | https://doi.org/10.1186/s13048-024-01534-w |
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| author | Yue Ma Weihua Nong Ou Zhong Ke Liu Siyuan Lei Chen Wang Xi Chen Xiaocan Lei |
| author_facet | Yue Ma Weihua Nong Ou Zhong Ke Liu Siyuan Lei Chen Wang Xi Chen Xiaocan Lei |
| author_sort | Yue Ma |
| collection | DOAJ |
| description | Abstract Background Premature ovarian insufficiency (POI) is a common clinical problem, but there is currently no effective treatment. NLRP3 inflammasome-induced pyroptosis is thought to be a possible mechanism of POI. Nicotinamide mononucleotide (NMN) has a certain anti-inflammatory effect, providing a promising approach for the treatment of POI. Methods Thirty female Sprague Dawley rats were randomly divided into a control group (n = 10) and a POI group (n = 20). Cyclophosphamide (CTX) was administered for 2 weeks to induce POI. Then the POI group was divided into two groups: the CTX-POI group (n = 10), which was given saline; and the CTX-POI + NMN group (n = 10), which was given NMN at a dose of 500 mg/kg/day for 21 consecutive days. At the end of the study, the serum hormone concentrations of each group were determined, and each group was subjected to biochemical, histopathological, and immunohistochemical analyses. In the in vitro experiment, cell pyroptosis was simulated by using lipopolysaccharide (LPS) and nigricin (Nig), and then KGN cells were treated with NMN, MCC950, and AGK2, and the levels of Nicotinamide adenine dinucleotide (NAD+) and inflammatory factors Interleukin-18(IL-18) and Interleukin-1β(IL-1β) in the cell supernatants were detected, and the levels of pyroptosis-related factors in the cells were determined. Results In POI rats, NMN treatments can improve blood hormone levels and partially improve the number of follicles, enhance ovarian reserve function and ovarian index.The evidence is that the increase in NAD+ levels and the activation of SIRT2 expression can reduce the expression of NLRP3, Gasdermin D (GSDMD), Caspase-1, IL-18, and IL-1β in the ovary. Conclusion NMN improves CTX-induced POI by inhibiting NLRP3-mediated pyroptosis, providing a new therapeutic strategy and drug target for clinical POI patients. |
| format | Article |
| id | doaj-art-52df2a48ace64a868c7633e4ecc08998 |
| institution | Kabale University |
| issn | 1757-2215 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Ovarian Research |
| spelling | doaj-art-52df2a48ace64a868c7633e4ecc089982024-12-01T12:40:06ZengBMCJournal of Ovarian Research1757-22152024-11-0117111410.1186/s13048-024-01534-wNicotinamide mononucleotide improves the ovarian reserve of POI by inhibiting NLRP3-mediated pyroptosis of ovarian granulosa cellsYue Ma0Weihua Nong1Ou Zhong2Ke Liu3Siyuan Lei4Chen Wang5Xi Chen6Xiaocan Lei7Institute of Clinical Anatomy & Reproductive Medicine, Department of Histology and Embryology Hengyang Medical School, University of South China HengyangKey Laboratory of Research on Clinical Molecular Diagnosis for High Incidence Diseases in Western Guangxi, Department of Obstetrics and Gynecology, Department of Reproductive Medicine Center, Affiliated Hospital of Youjiang Medical University for NationalitiesInstitute of Clinical Anatomy & Reproductive Medicine, Department of Histology and Embryology Hengyang Medical School, University of South China HengyangInstitute of Clinical Anatomy & Reproductive Medicine, Department of Histology and Embryology Hengyang Medical School, University of South China HengyangInstitute of Clinical Anatomy & Reproductive Medicine, Department of Histology and Embryology Hengyang Medical School, University of South China HengyangInstitute of Clinical Anatomy & Reproductive Medicine, Department of Histology and Embryology Hengyang Medical School, University of South China HengyangInstitute of Clinical Anatomy & Reproductive Medicine, Department of Histology and Embryology Hengyang Medical School, University of South China HengyangInstitute of Clinical Anatomy & Reproductive Medicine, Department of Histology and Embryology Hengyang Medical School, University of South China HengyangAbstract Background Premature ovarian insufficiency (POI) is a common clinical problem, but there is currently no effective treatment. NLRP3 inflammasome-induced pyroptosis is thought to be a possible mechanism of POI. Nicotinamide mononucleotide (NMN) has a certain anti-inflammatory effect, providing a promising approach for the treatment of POI. Methods Thirty female Sprague Dawley rats were randomly divided into a control group (n = 10) and a POI group (n = 20). Cyclophosphamide (CTX) was administered for 2 weeks to induce POI. Then the POI group was divided into two groups: the CTX-POI group (n = 10), which was given saline; and the CTX-POI + NMN group (n = 10), which was given NMN at a dose of 500 mg/kg/day for 21 consecutive days. At the end of the study, the serum hormone concentrations of each group were determined, and each group was subjected to biochemical, histopathological, and immunohistochemical analyses. In the in vitro experiment, cell pyroptosis was simulated by using lipopolysaccharide (LPS) and nigricin (Nig), and then KGN cells were treated with NMN, MCC950, and AGK2, and the levels of Nicotinamide adenine dinucleotide (NAD+) and inflammatory factors Interleukin-18(IL-18) and Interleukin-1β(IL-1β) in the cell supernatants were detected, and the levels of pyroptosis-related factors in the cells were determined. Results In POI rats, NMN treatments can improve blood hormone levels and partially improve the number of follicles, enhance ovarian reserve function and ovarian index.The evidence is that the increase in NAD+ levels and the activation of SIRT2 expression can reduce the expression of NLRP3, Gasdermin D (GSDMD), Caspase-1, IL-18, and IL-1β in the ovary. Conclusion NMN improves CTX-induced POI by inhibiting NLRP3-mediated pyroptosis, providing a new therapeutic strategy and drug target for clinical POI patients.https://doi.org/10.1186/s13048-024-01534-wNicotinamide mononucleotidePremature ovarian insufficiencyPyroptosis |
| spellingShingle | Yue Ma Weihua Nong Ou Zhong Ke Liu Siyuan Lei Chen Wang Xi Chen Xiaocan Lei Nicotinamide mononucleotide improves the ovarian reserve of POI by inhibiting NLRP3-mediated pyroptosis of ovarian granulosa cells Journal of Ovarian Research Nicotinamide mononucleotide Premature ovarian insufficiency Pyroptosis |
| title | Nicotinamide mononucleotide improves the ovarian reserve of POI by inhibiting NLRP3-mediated pyroptosis of ovarian granulosa cells |
| title_full | Nicotinamide mononucleotide improves the ovarian reserve of POI by inhibiting NLRP3-mediated pyroptosis of ovarian granulosa cells |
| title_fullStr | Nicotinamide mononucleotide improves the ovarian reserve of POI by inhibiting NLRP3-mediated pyroptosis of ovarian granulosa cells |
| title_full_unstemmed | Nicotinamide mononucleotide improves the ovarian reserve of POI by inhibiting NLRP3-mediated pyroptosis of ovarian granulosa cells |
| title_short | Nicotinamide mononucleotide improves the ovarian reserve of POI by inhibiting NLRP3-mediated pyroptosis of ovarian granulosa cells |
| title_sort | nicotinamide mononucleotide improves the ovarian reserve of poi by inhibiting nlrp3 mediated pyroptosis of ovarian granulosa cells |
| topic | Nicotinamide mononucleotide Premature ovarian insufficiency Pyroptosis |
| url | https://doi.org/10.1186/s13048-024-01534-w |
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