Toxic effect window of ovarian development in female offspring mice induced by prenatal prednisone exposure with different doses and time
Abstract Background Prednisone is one of the most used synthetic glucocorticoids during pregnancy. Epidemiological investigations suggested that prenatal prednisone therapy could affect fetal development, but systematic studies on its effects on ovarian development and the “toxic effect window” rema...
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| Format: | Article |
| Language: | English |
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BMC
2023-04-01
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| Series: | Journal of Ovarian Research |
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| Online Access: | https://doi.org/10.1186/s13048-023-01148-8 |
| _version_ | 1797845795932733440 |
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| author | Jing Huang Tiancheng Wu Yating Li Yuanzhen Zhang Xingjiang Yu Dan Xu Hui Wang |
| author_facet | Jing Huang Tiancheng Wu Yating Li Yuanzhen Zhang Xingjiang Yu Dan Xu Hui Wang |
| author_sort | Jing Huang |
| collection | DOAJ |
| description | Abstract Background Prednisone is one of the most used synthetic glucocorticoids during pregnancy. Epidemiological investigations suggested that prenatal prednisone therapy could affect fetal development, but systematic studies on its effects on ovarian development and the “toxic effect window” remained scarce. Methods In this study, by simulating clinical application characteristics, Kunming mice were given prednisone by oral gavage with different doses (0.25 or 1.0 mg/kg·d) or at different time gestational days (GD) (GD0-9, GD10-18, or GD0-18). Blood and ovaries of fetal mice were collected on GD18, and the serum estradiol level and the related function indexes of ovarian granulosa cells and oocytes were detected. Results Compared with the control group, prenatal prednisone exposure (PPE) induced pathological injury and enhanced cell proliferation in fetal mice ovary. Furthermore, the expression of steroid synthesis functional genes in pre-granulosa cells, the oocyte function markers, and developmentally related genes was enhanced with different doses or at different time of PPE. The Hippo signaling was activated in the fetal ovary of PPE groups. The above changes were most significant in the low or high-dose and full-term PPE groups. Conclusion PPE caused various cell developmental toxicity in the fetal ovary, especially in the low or high-dose, full-term exposure groups. The potential mechanism might be related to the activation of the Hippo signaling pathway. |
| first_indexed | 2024-04-09T17:44:42Z |
| format | Article |
| id | doaj.art-230db391ace84228b0e97ee4536a6265 |
| institution | Directory Open Access Journal |
| issn | 1757-2215 |
| language | English |
| last_indexed | 2024-04-09T17:44:42Z |
| publishDate | 2023-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Ovarian Research |
| spelling | doaj.art-230db391ace84228b0e97ee4536a62652023-04-16T11:22:16ZengBMCJournal of Ovarian Research1757-22152023-04-0116111210.1186/s13048-023-01148-8Toxic effect window of ovarian development in female offspring mice induced by prenatal prednisone exposure with different doses and timeJing Huang0Tiancheng Wu1Yating Li2Yuanzhen Zhang3Xingjiang Yu4Dan Xu5Hui Wang6Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan UniversityDepartment of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan UniversityDepartment of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan UniversityDepartment of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan UniversityDepartment of Histology and Embryology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pharmacy, School of Pharmaceutical Sciences, Zhongnan Hospital of Wuhan University, Wuhan UniversityDepartment of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan UniversityAbstract Background Prednisone is one of the most used synthetic glucocorticoids during pregnancy. Epidemiological investigations suggested that prenatal prednisone therapy could affect fetal development, but systematic studies on its effects on ovarian development and the “toxic effect window” remained scarce. Methods In this study, by simulating clinical application characteristics, Kunming mice were given prednisone by oral gavage with different doses (0.25 or 1.0 mg/kg·d) or at different time gestational days (GD) (GD0-9, GD10-18, or GD0-18). Blood and ovaries of fetal mice were collected on GD18, and the serum estradiol level and the related function indexes of ovarian granulosa cells and oocytes were detected. Results Compared with the control group, prenatal prednisone exposure (PPE) induced pathological injury and enhanced cell proliferation in fetal mice ovary. Furthermore, the expression of steroid synthesis functional genes in pre-granulosa cells, the oocyte function markers, and developmentally related genes was enhanced with different doses or at different time of PPE. The Hippo signaling was activated in the fetal ovary of PPE groups. The above changes were most significant in the low or high-dose and full-term PPE groups. Conclusion PPE caused various cell developmental toxicity in the fetal ovary, especially in the low or high-dose, full-term exposure groups. The potential mechanism might be related to the activation of the Hippo signaling pathway.https://doi.org/10.1186/s13048-023-01148-8PrednisonePrenatal exposureOvarian developmental toxicityPre-granulosa cellOocyte |
| spellingShingle | Jing Huang Tiancheng Wu Yating Li Yuanzhen Zhang Xingjiang Yu Dan Xu Hui Wang Toxic effect window of ovarian development in female offspring mice induced by prenatal prednisone exposure with different doses and time Journal of Ovarian Research Prednisone Prenatal exposure Ovarian developmental toxicity Pre-granulosa cell Oocyte |
| title | Toxic effect window of ovarian development in female offspring mice induced by prenatal prednisone exposure with different doses and time |
| title_full | Toxic effect window of ovarian development in female offspring mice induced by prenatal prednisone exposure with different doses and time |
| title_fullStr | Toxic effect window of ovarian development in female offspring mice induced by prenatal prednisone exposure with different doses and time |
| title_full_unstemmed | Toxic effect window of ovarian development in female offspring mice induced by prenatal prednisone exposure with different doses and time |
| title_short | Toxic effect window of ovarian development in female offspring mice induced by prenatal prednisone exposure with different doses and time |
| title_sort | toxic effect window of ovarian development in female offspring mice induced by prenatal prednisone exposure with different doses and time |
| topic | Prednisone Prenatal exposure Ovarian developmental toxicity Pre-granulosa cell Oocyte |
| url | https://doi.org/10.1186/s13048-023-01148-8 |
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