Adenovirus-mediated Sirt1 and Tgfbr2 gene therapy improves fertility in natural ovarian aging and doxorubicin-induced premature ovarian insufficiency mice
Premature ovarian insufficiency (POI) may lead to early menopause, fertility loss and birth defects without effective treatment. Here, we explored the efficacy and safety of gene therapy to rescue ovarian function in both natural ovarian aging and doxorubicin (Dox) induced POI mice. Sirt1 and Tgfbr2...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | Materials & Design |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0264127524000650 |
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| author | Lingwei Ma Huan Lu Xiaofan Gao Yue Su Yanzhi Feng Qianyu Zhang Peiya Fan Qian Chen Jingyi Wen Tong Wu Yan Zhang Bo Wang Xianan Tang Yueyue Gao Yan Li Su Zhou Meng Wu Pengfei Cui Jinjin Zhang Shixuan Wang |
| author_facet | Lingwei Ma Huan Lu Xiaofan Gao Yue Su Yanzhi Feng Qianyu Zhang Peiya Fan Qian Chen Jingyi Wen Tong Wu Yan Zhang Bo Wang Xianan Tang Yueyue Gao Yan Li Su Zhou Meng Wu Pengfei Cui Jinjin Zhang Shixuan Wang |
| author_sort | Lingwei Ma |
| collection | DOAJ |
| description | Premature ovarian insufficiency (POI) may lead to early menopause, fertility loss and birth defects without effective treatment. Here, we explored the efficacy and safety of gene therapy to rescue ovarian function in both natural ovarian aging and doxorubicin (Dox) induced POI mice. Sirt1 and Tgfbr2 were screened out and identified as key genes in both murine and human ovarian tissues. Then, adenovirus (AdV) was selected as a suited carrier for ovarian infection after comparison of multiple viral vectors. In both two models, murine fertility was significantly improved after AdV-Sirt1 and AdV-Tgfbr2 invention individually or in combination, without obvious side effects to themselves and their offspring. Compared with the control group, the successful pregnancy rate in the 9-month-old-AdV-Sirt1 group increased by 60 % (67 % vs 42 %). Meanwhile, the pregnancy rate in the AdV-Tgfbr2 + Dox group increased by 85 % (55.6 % vs 20 %). The biological process of ovarian follicle development and fibrosis was rescued. Our work demonstrated that AdV-Sirt1 and AdV-Tgfbr2 therapy alleviates natural ovarian aging and Dox-associated POI, which may be potentially applicable for female fertility protection. |
| first_indexed | 2024-03-07T23:25:11Z |
| format | Article |
| id | doaj.art-d87e382d069140f4a050e1a91e3c02e1 |
| institution | Directory Open Access Journal |
| issn | 0264-1275 |
| language | English |
| last_indexed | 2024-03-07T23:25:11Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials & Design |
| spelling | doaj.art-d87e382d069140f4a050e1a91e3c02e12024-02-21T05:24:06ZengElsevierMaterials & Design0264-12752024-02-01238112693Adenovirus-mediated Sirt1 and Tgfbr2 gene therapy improves fertility in natural ovarian aging and doxorubicin-induced premature ovarian insufficiency miceLingwei Ma0Huan Lu1Xiaofan Gao2Yue Su3Yanzhi Feng4Qianyu Zhang5Peiya Fan6Qian Chen7Jingyi Wen8Tong Wu9Yan Zhang10Bo Wang11Xianan Tang12Yueyue Gao13Yan Li14Su Zhou15Meng Wu16Pengfei Cui17Jinjin Zhang18Shixuan Wang19Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China; National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan 430030, Hubei, China; Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan 430030, Hubei, ChinaDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan 430030, Hubei, China; Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan 430030, Hubei, ChinaDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan 430030, Hubei, China; Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan 430030, Hubei, ChinaDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan 430030, Hubei, China; Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan 430030, Hubei, ChinaDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan 430030, Hubei, China; Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan 430030, Hubei, ChinaDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan 430030, Hubei, China; Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan 430030, Hubei, ChinaDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan 430030, Hubei, China; Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan 430030, Hubei, ChinaDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan 430030, Hubei, China; Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan 430030, Hubei, ChinaDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan 430030, Hubei, China; Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan 430030, Hubei, ChinaDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan 430030, Hubei, China; Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan 430030, Hubei, ChinaDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan 430030, Hubei, China; Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan 430030, Hubei, ChinaDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan 430030, Hubei, China; Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan 430030, Hubei, ChinaDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan 430030, Hubei, China; Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan 430030, Hubei, ChinaDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan 430030, Hubei, China; Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan 430030, Hubei, ChinaDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan 430030, Hubei, China; Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan 430030, Hubei, ChinaDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan 430030, Hubei, China; Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan 430030, Hubei, ChinaDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan 430030, Hubei, China; Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan 430030, Hubei, ChinaDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan 430030, Hubei, China; Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan 430030, Hubei, ChinaDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan 430030, Hubei, China; Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan 430030, Hubei, China; Corresponding authors at: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China (S. Wang)Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan 430030, Hubei, China; Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan 430030, Hubei, China; Corresponding authors at: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China (S. Wang)Premature ovarian insufficiency (POI) may lead to early menopause, fertility loss and birth defects without effective treatment. Here, we explored the efficacy and safety of gene therapy to rescue ovarian function in both natural ovarian aging and doxorubicin (Dox) induced POI mice. Sirt1 and Tgfbr2 were screened out and identified as key genes in both murine and human ovarian tissues. Then, adenovirus (AdV) was selected as a suited carrier for ovarian infection after comparison of multiple viral vectors. In both two models, murine fertility was significantly improved after AdV-Sirt1 and AdV-Tgfbr2 invention individually or in combination, without obvious side effects to themselves and their offspring. Compared with the control group, the successful pregnancy rate in the 9-month-old-AdV-Sirt1 group increased by 60 % (67 % vs 42 %). Meanwhile, the pregnancy rate in the AdV-Tgfbr2 + Dox group increased by 85 % (55.6 % vs 20 %). The biological process of ovarian follicle development and fibrosis was rescued. Our work demonstrated that AdV-Sirt1 and AdV-Tgfbr2 therapy alleviates natural ovarian aging and Dox-associated POI, which may be potentially applicable for female fertility protection.http://www.sciencedirect.com/science/article/pii/S0264127524000650FertilityGene therapyOvarian agingPremature ovarian insufficiency |
| spellingShingle | Lingwei Ma Huan Lu Xiaofan Gao Yue Su Yanzhi Feng Qianyu Zhang Peiya Fan Qian Chen Jingyi Wen Tong Wu Yan Zhang Bo Wang Xianan Tang Yueyue Gao Yan Li Su Zhou Meng Wu Pengfei Cui Jinjin Zhang Shixuan Wang Adenovirus-mediated Sirt1 and Tgfbr2 gene therapy improves fertility in natural ovarian aging and doxorubicin-induced premature ovarian insufficiency mice Materials & Design Fertility Gene therapy Ovarian aging Premature ovarian insufficiency |
| title | Adenovirus-mediated Sirt1 and Tgfbr2 gene therapy improves fertility in natural ovarian aging and doxorubicin-induced premature ovarian insufficiency mice |
| title_full | Adenovirus-mediated Sirt1 and Tgfbr2 gene therapy improves fertility in natural ovarian aging and doxorubicin-induced premature ovarian insufficiency mice |
| title_fullStr | Adenovirus-mediated Sirt1 and Tgfbr2 gene therapy improves fertility in natural ovarian aging and doxorubicin-induced premature ovarian insufficiency mice |
| title_full_unstemmed | Adenovirus-mediated Sirt1 and Tgfbr2 gene therapy improves fertility in natural ovarian aging and doxorubicin-induced premature ovarian insufficiency mice |
| title_short | Adenovirus-mediated Sirt1 and Tgfbr2 gene therapy improves fertility in natural ovarian aging and doxorubicin-induced premature ovarian insufficiency mice |
| title_sort | adenovirus mediated sirt1 and tgfbr2 gene therapy improves fertility in natural ovarian aging and doxorubicin induced premature ovarian insufficiency mice |
| topic | Fertility Gene therapy Ovarian aging Premature ovarian insufficiency |
| url | http://www.sciencedirect.com/science/article/pii/S0264127524000650 |
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