p38 mediates T-2 toxin-induced Leydig cell testosterone synthesis disorder

T-2 toxin is an unavoidable food and feed contaminant that seriously threatens human and animal health. Exposure to T-2 toxin can cause testosterone synthesis disorder in male animals, but the molecular mechanism is still not completely clear. The MAPK pathway participates in the regulation of testo...

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Main Authors: Xu Yang, Wenxi Song, Kefei Zhang, Youshuang Wang, Fengjuan Chen, Yunhe Chen, Tingyu Huang, Yibao Jiang, Xuebing Wang, Cong Zhang
Format: Article
Language:English
Published: Elsevier 2023-03-01
Series:Ecotoxicology and Environmental Safety
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0147651323001999
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author Xu Yang
Wenxi Song
Kefei Zhang
Youshuang Wang
Fengjuan Chen
Yunhe Chen
Tingyu Huang
Yibao Jiang
Xuebing Wang
Cong Zhang
author_facet Xu Yang
Wenxi Song
Kefei Zhang
Youshuang Wang
Fengjuan Chen
Yunhe Chen
Tingyu Huang
Yibao Jiang
Xuebing Wang
Cong Zhang
author_sort Xu Yang
collection DOAJ
description T-2 toxin is an unavoidable food and feed contaminant that seriously threatens human and animal health. Exposure to T-2 toxin can cause testosterone synthesis disorder in male animals, but the molecular mechanism is still not completely clear. The MAPK pathway participates in the regulation of testosterone synthesis by Leydig cells, but it is unclear whether the MAPK pathway participates in T-2 toxin-induced testosterone synthesis disorders. In this research, testosterone synthesis capacity, testosterone synthase expression and MAPK pathway activation were examined in male mice and TM3 cells exposed to T-2 toxin. The results showed that T-2 toxin exposure decreased testicular volume and caused pathological changes in the microstructure and ultrastructure of testicular Leydig cells. T-2 toxin exposure also decreased testicular testosterone content and the protein expression of testosterone synthase. In vitro, T-2 toxin inhibited cell viability and decreased the expression of testosterone synthase in TM3 cells, and it decreased the testosterone contents in cell culture supernatants. Moreover, T-2 toxin activated the MAPK pathway by increasing the expression of p38, JNK and ERK as well as the expression of p-p38, p-JNK and p-ERK in testis and TM3 cells. The p38 molecular inhibitor (SB203580) significantly alleviated the T-2 toxin-induced decrease in testosterone synthase expression in TM3 cells and the T-2 toxin-induced reduction in testosterone content in TM3 cell culture supernatants. In summary, p38 mediates T-2 toxin-induced Leydig cell testosterone synthesis disorder.
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spelling doaj.art-4e9cf79cae7e4f0ab17691c342911d902023-03-16T05:01:25ZengElsevierEcotoxicology and Environmental Safety0147-65132023-03-01253114695p38 mediates T-2 toxin-induced Leydig cell testosterone synthesis disorderXu Yang0Wenxi Song1Kefei Zhang2Youshuang Wang3Fengjuan Chen4Yunhe Chen5Tingyu Huang6Yibao Jiang7Xuebing Wang8Cong Zhang9College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan, ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan, ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan, ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan, ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan, ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan, ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan, ChinaCollege of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450002, Henan, ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan, ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan, China; International Joint Research Center of National Animal Immunology, College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China; Correspondence to: College of Veterinary Medicine, Henan Agricultural University, No. 15, Longzihu University Park, Zhengdong New District, Zhengzhou 450046, People’s Republic of China.T-2 toxin is an unavoidable food and feed contaminant that seriously threatens human and animal health. Exposure to T-2 toxin can cause testosterone synthesis disorder in male animals, but the molecular mechanism is still not completely clear. The MAPK pathway participates in the regulation of testosterone synthesis by Leydig cells, but it is unclear whether the MAPK pathway participates in T-2 toxin-induced testosterone synthesis disorders. In this research, testosterone synthesis capacity, testosterone synthase expression and MAPK pathway activation were examined in male mice and TM3 cells exposed to T-2 toxin. The results showed that T-2 toxin exposure decreased testicular volume and caused pathological changes in the microstructure and ultrastructure of testicular Leydig cells. T-2 toxin exposure also decreased testicular testosterone content and the protein expression of testosterone synthase. In vitro, T-2 toxin inhibited cell viability and decreased the expression of testosterone synthase in TM3 cells, and it decreased the testosterone contents in cell culture supernatants. Moreover, T-2 toxin activated the MAPK pathway by increasing the expression of p38, JNK and ERK as well as the expression of p-p38, p-JNK and p-ERK in testis and TM3 cells. The p38 molecular inhibitor (SB203580) significantly alleviated the T-2 toxin-induced decrease in testosterone synthase expression in TM3 cells and the T-2 toxin-induced reduction in testosterone content in TM3 cell culture supernatants. In summary, p38 mediates T-2 toxin-induced Leydig cell testosterone synthesis disorder.http://www.sciencedirect.com/science/article/pii/S0147651323001999T-2 toxinTestosterone synthesisMAPK signaling pathwayTestis
spellingShingle Xu Yang
Wenxi Song
Kefei Zhang
Youshuang Wang
Fengjuan Chen
Yunhe Chen
Tingyu Huang
Yibao Jiang
Xuebing Wang
Cong Zhang
p38 mediates T-2 toxin-induced Leydig cell testosterone synthesis disorder
Ecotoxicology and Environmental Safety
T-2 toxin
Testosterone synthesis
MAPK signaling pathway
Testis
title p38 mediates T-2 toxin-induced Leydig cell testosterone synthesis disorder
title_full p38 mediates T-2 toxin-induced Leydig cell testosterone synthesis disorder
title_fullStr p38 mediates T-2 toxin-induced Leydig cell testosterone synthesis disorder
title_full_unstemmed p38 mediates T-2 toxin-induced Leydig cell testosterone synthesis disorder
title_short p38 mediates T-2 toxin-induced Leydig cell testosterone synthesis disorder
title_sort p38 mediates t 2 toxin induced leydig cell testosterone synthesis disorder
topic T-2 toxin
Testosterone synthesis
MAPK signaling pathway
Testis
url http://www.sciencedirect.com/science/article/pii/S0147651323001999
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