PMID- 37038227 OWN - NLM STAT- MEDLINE DCOM- 20230412 LR - 20230413 IS - 1757-2215 (Electronic) IS - 1757-2215 (Linking) VI - 16 IP - 1 DP - 2023 Apr 11 TI - Toxic effect window of ovarian development in female offspring mice induced by prenatal prednisone exposure with different doses and time. PG - 71 LID - 10.1186/s13048-023-01148-8 [doi] LID - 71 AB - 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. CI - (c) 2023. The Author(s). FAU - Huang, Jing AU - Huang J AD - Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. AD - Department of Otorhinolaryngology Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. AD - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China. FAU - Wu, Tiancheng AU - Wu T AD - Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. AD - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China. FAU - Li, Yating AU - Li Y AD - Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. AD - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China. FAU - Zhang, Yuanzhen AU - Zhang Y AD - Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. AD - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China. FAU - Yu, Xingjiang AU - Yu X AD - Department of Histology and Embryology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. yuxingjiang@hust.edu.cn. FAU - Xu, Dan AU - Xu D AD - Department of Pharmacy, School of Pharmaceutical Sciences, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, China. xuyidan70188@whu.edu.cn. AD - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China. xuyidan70188@whu.edu.cn. FAU - Wang, Hui AU - Wang H AD - Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. wanghui19@whu.edu.cn. AD - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, 430071, China. wanghui19@whu.edu.cn. AD - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China. wanghui19@whu.edu.cn. LA - eng GR - No. 2020YFA0803900/National Key Research and Development Program of China/ GR - No. 81903729, 82030111/National Natural Science Foundation of China/ PT - Journal Article DEP - 20230411 PL - England TA - J Ovarian Res JT - Journal of ovarian research JID - 101474849 RN - 4TI98Z838E (Estradiol) RN - VB0R961HZT (Prednisone) RN - Kunming mice SB - IM MH - Mice MH - Pregnancy MH - Female MH - Animals MH - *Estradiol MH - Prednisone/metabolism/pharmacology MH - *Ovary MH - Oocytes/metabolism PMC - PMC10088227 OTO - NOTNLM OT - Oocyte OT - Ovarian developmental toxicity OT - Pre-granulosa cell OT - Prednisone OT - Prenatal exposure COIS- On behalf of all authors, the corresponding author states that there is no conflict of interest. EDAT- 2023/04/11 06:00 MHDA- 2023/04/12 06:41 PMCR- 2023/04/11 CRDT- 2023/04/10 23:50 PHST- 2022/12/14 00:00 [received] PHST- 2023/03/29 00:00 [accepted] PHST- 2023/04/12 06:41 [medline] PHST- 2023/04/10 23:50 [entrez] PHST- 2023/04/11 06:00 [pubmed] PHST- 2023/04/11 00:00 [pmc-release] AID - 10.1186/s13048-023-01148-8 [pii] AID - 1148 [pii] AID - 10.1186/s13048-023-01148-8 [doi] PST - epublish SO - J Ovarian Res. 2023 Apr 11;16(1):71. doi: 10.1186/s13048-023-01148-8.