Cyclopiazonic acid suppresses the function of Leydig cells in prepubertal male rats by disrupting mitofusin 1-mediated mitochondrial function
This research investigated the impact of cyclopiazonic acid (CPA), a mycotoxin, on the function of progenitor Leydig cells (PLCs) in prepubertal male rats, focusing on its potential disruption of mitochondrial integrity through mitofusin 1 (MFN1) modulation. In vivo, Sprague Dawley rats received CPA...
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Elsevier
2025-01-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651324015793 |
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| author | Hang Lin Ming Su He Zhu Yang Yu Jianmin Sang Yiyan Wang Qiqi Zhu Yang Zhu Xiaoheng Li Xingwang Li Ren-Shan Ge Huitao Li |
| author_facet | Hang Lin Ming Su He Zhu Yang Yu Jianmin Sang Yiyan Wang Qiqi Zhu Yang Zhu Xiaoheng Li Xingwang Li Ren-Shan Ge Huitao Li |
| author_sort | Hang Lin |
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| description | This research investigated the impact of cyclopiazonic acid (CPA), a mycotoxin, on the function of progenitor Leydig cells (PLCs) in prepubertal male rats, focusing on its potential disruption of mitochondrial integrity through mitofusin 1 (MFN1) modulation. In vivo, Sprague Dawley rats received CPA (0.2, 1, 5 mg/kg/day) via gavage from postnatal days 21–28 to evaluate PLC function and mitochondrial morphology using serum hormone levels, histology, qPCR, and Western blot analyses. In vitro, rat R2C cells were treated with CPA (0.1, 1, 10 μM) alone or in combination with 100 μM leflunomide to assess PLC development through testosterone measurements, Western blotting, flow cytometry, and Mito-Tracker Green Staining. The findings from in vivo experiments showed that CPA reduced serum testosterone and progesterone levels at 1 mg/kg/day. The qPCR and Western blotting analyses revealed significant alterations in the expression of genes and proteins pertinent to PLC function, such as Scarb1, Star, Cyp11a1, and Cyp17a1. Immunofluorescence staining further revealed a reduction in MFN1 expression following exposure to CPA. In vitro experiments corroborated these observations, demonstrating that CPA induced mitochondrial fragmentation by downregulating SIRT1, PGC1-α, MFN1, and OPA1, increase reactive oxygen species, and inhibit testosterone synthesis in R2C cells. The administration of leflunomide was shown to mitigate the detrimental effects of CPA on PLCs. In conclusion, this research sheds new light on the deleterious effects of CPA on the reproductive development of prepubertal males. |
| format | Article |
| id | doaj-art-0f2459cbfb5d4b43b1e8a564e4202550 |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-0f2459cbfb5d4b43b1e8a564e42025502025-01-23T05:25:48ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01289117503Cyclopiazonic acid suppresses the function of Leydig cells in prepubertal male rats by disrupting mitofusin 1-mediated mitochondrial functionHang Lin0Ming Su1He Zhu2Yang Yu3Jianmin Sang4Yiyan Wang5Qiqi Zhu6Yang Zhu7Xiaoheng Li8Xingwang Li9Ren-Shan Ge10Huitao Li11Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Environment and Male Reproductive Medicine of Wenzhou, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, ChinaDepartment of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Environment and Male Reproductive Medicine of Wenzhou, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, ChinaDepartment of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Environment and Male Reproductive Medicine of Wenzhou, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, ChinaDepartment of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Environment and Male Reproductive Medicine of Wenzhou, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, ChinaDepartment of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Environment and Male Reproductive Medicine of Wenzhou, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, ChinaDepartment of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Environment and Male Reproductive Medicine of Wenzhou, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, ChinaDepartment of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Environment and Male Reproductive Medicine of Wenzhou, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, ChinaDepartment of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Environment and Male Reproductive Medicine of Wenzhou, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, ChinaDepartment of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Environment and Male Reproductive Medicine of Wenzhou, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, ChinaDepartment of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325000, ChinaDepartment of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Environment and Male Reproductive Medicine of Wenzhou, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Correspondence to: Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital the Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Zhejiang Engineering Research Center for Innovation and Application of Intelligent Radiotherapy Technology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Wenzhou key Laboratory of basic science and translational research of radiation oncology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Key Laboratory of Environment and Male Reproductive Medicine of Wenzhou, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Correspondence to: Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital the Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.This research investigated the impact of cyclopiazonic acid (CPA), a mycotoxin, on the function of progenitor Leydig cells (PLCs) in prepubertal male rats, focusing on its potential disruption of mitochondrial integrity through mitofusin 1 (MFN1) modulation. In vivo, Sprague Dawley rats received CPA (0.2, 1, 5 mg/kg/day) via gavage from postnatal days 21–28 to evaluate PLC function and mitochondrial morphology using serum hormone levels, histology, qPCR, and Western blot analyses. In vitro, rat R2C cells were treated with CPA (0.1, 1, 10 μM) alone or in combination with 100 μM leflunomide to assess PLC development through testosterone measurements, Western blotting, flow cytometry, and Mito-Tracker Green Staining. The findings from in vivo experiments showed that CPA reduced serum testosterone and progesterone levels at 1 mg/kg/day. The qPCR and Western blotting analyses revealed significant alterations in the expression of genes and proteins pertinent to PLC function, such as Scarb1, Star, Cyp11a1, and Cyp17a1. Immunofluorescence staining further revealed a reduction in MFN1 expression following exposure to CPA. In vitro experiments corroborated these observations, demonstrating that CPA induced mitochondrial fragmentation by downregulating SIRT1, PGC1-α, MFN1, and OPA1, increase reactive oxygen species, and inhibit testosterone synthesis in R2C cells. The administration of leflunomide was shown to mitigate the detrimental effects of CPA on PLCs. In conclusion, this research sheds new light on the deleterious effects of CPA on the reproductive development of prepubertal males.http://www.sciencedirect.com/science/article/pii/S0147651324015793Cyclopiazonic acidProgenitor Leydig cellMitofusin 1Mitochondrial functionLeflunomide |
| spellingShingle | Hang Lin Ming Su He Zhu Yang Yu Jianmin Sang Yiyan Wang Qiqi Zhu Yang Zhu Xiaoheng Li Xingwang Li Ren-Shan Ge Huitao Li Cyclopiazonic acid suppresses the function of Leydig cells in prepubertal male rats by disrupting mitofusin 1-mediated mitochondrial function Ecotoxicology and Environmental Safety Cyclopiazonic acid Progenitor Leydig cell Mitofusin 1 Mitochondrial function Leflunomide |
| title | Cyclopiazonic acid suppresses the function of Leydig cells in prepubertal male rats by disrupting mitofusin 1-mediated mitochondrial function |
| title_full | Cyclopiazonic acid suppresses the function of Leydig cells in prepubertal male rats by disrupting mitofusin 1-mediated mitochondrial function |
| title_fullStr | Cyclopiazonic acid suppresses the function of Leydig cells in prepubertal male rats by disrupting mitofusin 1-mediated mitochondrial function |
| title_full_unstemmed | Cyclopiazonic acid suppresses the function of Leydig cells in prepubertal male rats by disrupting mitofusin 1-mediated mitochondrial function |
| title_short | Cyclopiazonic acid suppresses the function of Leydig cells in prepubertal male rats by disrupting mitofusin 1-mediated mitochondrial function |
| title_sort | cyclopiazonic acid suppresses the function of leydig cells in prepubertal male rats by disrupting mitofusin 1 mediated mitochondrial function |
| topic | Cyclopiazonic acid Progenitor Leydig cell Mitofusin 1 Mitochondrial function Leflunomide |
| url | http://www.sciencedirect.com/science/article/pii/S0147651324015793 |
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