PMID- 38008334 OWN - NLM STAT- MEDLINE DCOM- 20240118 LR - 20240118 IS - 1879-1026 (Electronic) IS - 0048-9697 (Linking) VI - 912 DP - 2024 Feb 20 TI - Gestodene causes masculinization of the western mosquitofish (Gambusia affinis): Insights from ovary metabolomics. PG - 168693 LID - S0048-9697(23)07321-7 [pii] LID - 10.1016/j.scitotenv.2023.168693 [doi] AB - Gestodene (GES) is a common synthetic progesterone frequently detected in aquatic environments. Chronic exposure to GES can cause masculinization of a variety of fish; however, whether metabolism is closely related to the masculinization has yet to be explored. Hence, the ovary metabolome of adult female western mosquitofish (Gambusia affinis) after exposing to GES (0.0, 5.0, 50.0, and 500.0 ng/L) for 40 days was analyzed by using high-performance liquid chromatography ionization with quadrupole time-of-flight tandem mass spectrometry (HPLC-QTOF-MS). The results showed that GES increased the levels of cysteine, taurine, ophthalmic acid and cAMP while decreased methionine, these metabolites changes may owing to the oxidative stress of the ovaries; while taurcholic acid and uric acid were decreased along with induced oocyte apopotosis. Steroids hormone metabolism was also significantly affected, with progesterone and cortisol being the most affected. Enzyme-linked immunoassay results showed that estradiol levels were decreased while testosterone levels were increased with GES exposure. In addition, correlation analysis showed that the differential metabolites of some amino acids (e.g. leucine) were strongly correlated with the levels of steroids hormones secreted by the pituitary gland. The results of this study suggest that GES affects ovarian metabolism via the hypothalamus-pituitary-gonad and hypothalamic-pituitary-adrenal axes, impair antioxidant capacity, induce apoptosis in the ovary of G. affinis, and finally caused masculinization. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Li, Yelin AU - Li Y AD - School of Life Sciences, Guangzhou University, Guangzhou 510006, China. FAU - Tan, Zhiqing AU - Tan Z AD - School of Life Sciences, Guangzhou University, Guangzhou 510006, China; School of Life Sciences, Zhaoqing University, Zhaoqing 526000, China. FAU - Zuo, Peiyu AU - Zuo P AD - School of Life Sciences, Guangzhou University, Guangzhou 510006, China. FAU - Li, Maorong AU - Li M AD - School of Life Sciences, Guangzhou University, Guangzhou 510006, China. FAU - Hou, Liping AU - Hou L AD - School of Life Sciences, Guangzhou University, Guangzhou 510006, China. Electronic address: houliping7710@163.com. FAU - Wang, Xiaolan AU - Wang X AD - School of Life Sciences, Guangzhou University, Guangzhou 510006, China. Electronic address: wxl1972@gzhu.edu.cn. LA - eng PT - Journal Article DEP - 20231124 PL - Netherlands TA - Sci Total Environ JT - The Science of the total environment JID - 0330500 RN - 4G7DS2Q64Y (Progesterone) RN - 1664P6E6MI (Gestodene) RN - 0 (Steroids) RN - 0 (Norpregnenes) SB - IM MH - Animals MH - Female MH - *Ovary MH - Progesterone/metabolism MH - Steroids/metabolism MH - *Cyprinodontiformes/metabolism MH - *Norpregnenes OTO - NOTNLM OT - Gambusia affinis OT - Gestodene OT - HPA axis OT - HPG axis OT - Metabolism OT - Ovary COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/11/27 00:43 MHDA- 2024/01/18 06:42 CRDT- 2023/11/26 19:27 PHST- 2023/09/22 00:00 [received] PHST- 2023/11/07 00:00 [revised] PHST- 2023/11/17 00:00 [accepted] PHST- 2024/01/18 06:42 [medline] PHST- 2023/11/27 00:43 [pubmed] PHST- 2023/11/26 19:27 [entrez] AID - S0048-9697(23)07321-7 [pii] AID - 10.1016/j.scitotenv.2023.168693 [doi] PST - ppublish SO - Sci Total Environ. 2024 Feb 20;912:168693. doi: 10.1016/j.scitotenv.2023.168693. Epub 2023 Nov 24.