Triclosan inhibits testosterone synthesis in male offspring by activating mitophagy

Triclosan (TCS), a typical endocrine disruptor, has been shown to interfere with testosterone biosynthesis in male animals. However, the effects and mechanisms of environmental TCS levels on testosterone synthesis in male mice offspring remain unclear. In this study, male mice offspring were exposed...

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Main Authors: Huili Lan, Yan Jiang, Lixiang Wu, Shushu Xie, Hui Huang, Dapeng Ji, Bingqi Zhu, Zhishan Ding, Jie Yu, Xiaoqing Ye
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Ecotoxicology and Environmental Safety
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Online Access:http://www.sciencedirect.com/science/article/pii/S0147651325008619
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author Huili Lan
Yan Jiang
Lixiang Wu
Shushu Xie
Hui Huang
Dapeng Ji
Bingqi Zhu
Zhishan Ding
Jie Yu
Xiaoqing Ye
author_facet Huili Lan
Yan Jiang
Lixiang Wu
Shushu Xie
Hui Huang
Dapeng Ji
Bingqi Zhu
Zhishan Ding
Jie Yu
Xiaoqing Ye
author_sort Huili Lan
collection DOAJ
description Triclosan (TCS), a typical endocrine disruptor, has been shown to interfere with testosterone biosynthesis in male animals. However, the effects and mechanisms of environmental TCS levels on testosterone synthesis in male mice offspring remain unclear. In this study, male mice offspring were exposed to TCS (0, 30, 300, and 3000 μg/kg/day) during prenatal and lactation periods, and Leydig (TM3) cells exposed to TCS (0, 30, 300 and 3000 nM) were used to establish an in vitro model. Results indicated that TCS exposure led to reduced testicular weight, organ coefficient, serum testosterone levels and steroidogenic enzyme activity, along with pathological changes in testicular tissue. RNA sequencing and lipid metabolome analysis suggested that TCS exposure may disrupt testicular lipid metabolism and is closely related to mitophagy and the PI3K/AKT/mTOR pathway. For in vitro experiments, TCS activated mitophagy in TM3 cells, characterized by elevated reactive oxygen species, mitochondrial damage, reduced mitochondrial membrane potential, formation of mitochondrial phagosomes and phagolysosomes, and altered expression of mitophagy-related proteins. TCS also decreased PI3K/AKT/mTOR pathway activity and steroidogenic enzyme expression, inhibiting testosterone secretion. In conclusion, environmental TCS levels inhibit testosterone synthesis in male offspring by inducing Leydig cell mitophagy, which may be linked to the suppression of the PI3K/AKT/mTOR pathway.
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spelling doaj-art-866d6fd595ed4d6c9fdd7ada81db05e22025-08-20T02:09:51ZengElsevierEcotoxicology and Environmental Safety0147-65132025-08-0130111851610.1016/j.ecoenv.2025.118516Triclosan inhibits testosterone synthesis in male offspring by activating mitophagyHuili Lan0Yan Jiang1Lixiang Wu2Shushu Xie3Hui Huang4Dapeng Ji5Bingqi Zhu6Zhishan Ding7Jie Yu8Xiaoqing Ye9School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaSchool of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaSchool of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaSchool of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaSchool of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaLogistics Management Office, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, ChinaSchool of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaSchool of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaPuer Kunhong Biotechnology Company, Group C of Chamagu Town A, Simao District, Puer, Yunnan 665000, ChinaSchool of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou 310053, China; Correspondence to: Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China.Triclosan (TCS), a typical endocrine disruptor, has been shown to interfere with testosterone biosynthesis in male animals. However, the effects and mechanisms of environmental TCS levels on testosterone synthesis in male mice offspring remain unclear. In this study, male mice offspring were exposed to TCS (0, 30, 300, and 3000 μg/kg/day) during prenatal and lactation periods, and Leydig (TM3) cells exposed to TCS (0, 30, 300 and 3000 nM) were used to establish an in vitro model. Results indicated that TCS exposure led to reduced testicular weight, organ coefficient, serum testosterone levels and steroidogenic enzyme activity, along with pathological changes in testicular tissue. RNA sequencing and lipid metabolome analysis suggested that TCS exposure may disrupt testicular lipid metabolism and is closely related to mitophagy and the PI3K/AKT/mTOR pathway. For in vitro experiments, TCS activated mitophagy in TM3 cells, characterized by elevated reactive oxygen species, mitochondrial damage, reduced mitochondrial membrane potential, formation of mitochondrial phagosomes and phagolysosomes, and altered expression of mitophagy-related proteins. TCS also decreased PI3K/AKT/mTOR pathway activity and steroidogenic enzyme expression, inhibiting testosterone secretion. In conclusion, environmental TCS levels inhibit testosterone synthesis in male offspring by inducing Leydig cell mitophagy, which may be linked to the suppression of the PI3K/AKT/mTOR pathway.http://www.sciencedirect.com/science/article/pii/S0147651325008619TriclosanMitophagyTestosteroneMale offspring
spellingShingle Huili Lan
Yan Jiang
Lixiang Wu
Shushu Xie
Hui Huang
Dapeng Ji
Bingqi Zhu
Zhishan Ding
Jie Yu
Xiaoqing Ye
Triclosan inhibits testosterone synthesis in male offspring by activating mitophagy
Ecotoxicology and Environmental Safety
Triclosan
Mitophagy
Testosterone
Male offspring
title Triclosan inhibits testosterone synthesis in male offspring by activating mitophagy
title_full Triclosan inhibits testosterone synthesis in male offspring by activating mitophagy
title_fullStr Triclosan inhibits testosterone synthesis in male offspring by activating mitophagy
title_full_unstemmed Triclosan inhibits testosterone synthesis in male offspring by activating mitophagy
title_short Triclosan inhibits testosterone synthesis in male offspring by activating mitophagy
title_sort triclosan inhibits testosterone synthesis in male offspring by activating mitophagy
topic Triclosan
Mitophagy
Testosterone
Male offspring
url http://www.sciencedirect.com/science/article/pii/S0147651325008619
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