Materials & Design (Feb 2024)
Adenovirus-mediated Sirt1 and Tgfbr2 gene therapy improves fertility in natural ovarian aging and doxorubicin-induced premature ovarian insufficiency mice
- 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
Affiliations
- Lingwei Ma
- Department 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, China
- Huan Lu
- 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
- Xiaofan Gao
- 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
- Yue Su
- 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
- Yanzhi Feng
- 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
- Qianyu Zhang
- 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
- Peiya Fan
- 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
- Qian Chen
- 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
- Jingyi Wen
- 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
- Tong Wu
- 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
- Yan Zhang
- 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
- Bo 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
- Xianan Tang
- 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
- Yueyue Gao
- 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
- Yan Li
- 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
- Su Zhou
- 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
- Meng Wu
- 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
- Pengfei Cui
- 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
- Jinjin Zhang
- 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)
- Shixuan 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)
- Journal volume & issue
-
Vol. 238
p. 112693
Abstract
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.
