Exposure to tris(2,4-di-tert-butylphenyl) phosphate during adolescence induces testicular toxicity in mice: Autophagy-apoptosis interplay

Tris(2,4-di-tert-butylphenyl) phosphate (AO168 = O), a novel organophosphate ester, has been widely utilized and is commonly exposed in various industries, posing significant threats to both ecological systems and public health. Adolescents are in a pivotal stage of development and are probably more...

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Main Authors: Xiangxiang Chen, Lihua Feng, Yanan Xia, Haoneng Li, Faqun Liu, Yang’e Li, Hengyi Xu, Yang Liu
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:Ecotoxicology and Environmental Safety
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Online Access:http://www.sciencedirect.com/science/article/pii/S0147651325009431
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author Xiangxiang Chen
Lihua Feng
Yanan Xia
Haoneng Li
Faqun Liu
Yang’e Li
Hengyi Xu
Yang Liu
author_facet Xiangxiang Chen
Lihua Feng
Yanan Xia
Haoneng Li
Faqun Liu
Yang’e Li
Hengyi Xu
Yang Liu
author_sort Xiangxiang Chen
collection DOAJ
description Tris(2,4-di-tert-butylphenyl) phosphate (AO168 = O), a novel organophosphate ester, has been widely utilized and is commonly exposed in various industries, posing significant threats to both ecological systems and public health. Adolescents are in a pivotal stage of development and are probably more susceptible to the effects of AO168 = O. In this experiment, 4-week-old male mice were given AO168 = O by daily gavage at doses of 0, 0.7, 7, or 70 μg/kg for 28 days. Then, we took the testes as the research subject and delved into the effects of exposure to AO168 = O during the developmental stage on male reproduction. The results demonstrate that AO168 = O can induce both reproductive and developmental toxicity in adolescent mice, manifesting as testicular structural damage, hormonal disturbances, and spermatogenic impairment. Further research suggested that AO168 = O triggered testicular autophagy by inducing oxidative stress, and finally, the interaction between autophagy and apoptosis resulted in testicular toxicity. Additionally, we found that one potential mechanism by which AO168 = O induces interplay between autophagy and apoptosis in testicular cells may involve activation of the ROS/JNK/Bcl-2 signaling pathway. This study clarifies that AO168 = O induces adverse effects in the male reproductive system during adolescence, highlighting specific reproductive risks in adolescents and providing scientific grounds for systematic health risk assessment.
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institution Kabale University
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publishDate 2025-09-01
publisher Elsevier
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series Ecotoxicology and Environmental Safety
spelling doaj-art-3dfa8a9cb6d44fc4a116fdb120dc87862025-08-20T03:41:05ZengElsevierEcotoxicology and Environmental Safety0147-65132025-09-0130211859810.1016/j.ecoenv.2025.118598Exposure to tris(2,4-di-tert-butylphenyl) phosphate during adolescence induces testicular toxicity in mice: Autophagy-apoptosis interplayXiangxiang Chen0Lihua Feng1Yanan Xia2Haoneng Li3Faqun Liu4Yang’e Li5Hengyi Xu6Yang Liu7Department of Pediatrics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, ChinaDepartment of Pediatrics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, ChinaDepartment of Pediatrics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, ChinaState Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, ChinaDepartment of Pediatrics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, ChinaDepartment of Pediatrics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, ChinaState Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, ChinaDepartment of Pediatrics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China; Correspondence to: Department of Pediatrics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1 Minde Road, Nanchang 330006, China.Tris(2,4-di-tert-butylphenyl) phosphate (AO168 = O), a novel organophosphate ester, has been widely utilized and is commonly exposed in various industries, posing significant threats to both ecological systems and public health. Adolescents are in a pivotal stage of development and are probably more susceptible to the effects of AO168 = O. In this experiment, 4-week-old male mice were given AO168 = O by daily gavage at doses of 0, 0.7, 7, or 70 μg/kg for 28 days. Then, we took the testes as the research subject and delved into the effects of exposure to AO168 = O during the developmental stage on male reproduction. The results demonstrate that AO168 = O can induce both reproductive and developmental toxicity in adolescent mice, manifesting as testicular structural damage, hormonal disturbances, and spermatogenic impairment. Further research suggested that AO168 = O triggered testicular autophagy by inducing oxidative stress, and finally, the interaction between autophagy and apoptosis resulted in testicular toxicity. Additionally, we found that one potential mechanism by which AO168 = O induces interplay between autophagy and apoptosis in testicular cells may involve activation of the ROS/JNK/Bcl-2 signaling pathway. This study clarifies that AO168 = O induces adverse effects in the male reproductive system during adolescence, highlighting specific reproductive risks in adolescents and providing scientific grounds for systematic health risk assessment.http://www.sciencedirect.com/science/article/pii/S0147651325009431Tris(24-di-tert-butylphenyl) phosphateAdolescent exposureTesticular toxicityAutophagyApoptosis
spellingShingle Xiangxiang Chen
Lihua Feng
Yanan Xia
Haoneng Li
Faqun Liu
Yang’e Li
Hengyi Xu
Yang Liu
Exposure to tris(2,4-di-tert-butylphenyl) phosphate during adolescence induces testicular toxicity in mice: Autophagy-apoptosis interplay
Ecotoxicology and Environmental Safety
Tris(2
4-di-tert-butylphenyl) phosphate
Adolescent exposure
Testicular toxicity
Autophagy
Apoptosis
title Exposure to tris(2,4-di-tert-butylphenyl) phosphate during adolescence induces testicular toxicity in mice: Autophagy-apoptosis interplay
title_full Exposure to tris(2,4-di-tert-butylphenyl) phosphate during adolescence induces testicular toxicity in mice: Autophagy-apoptosis interplay
title_fullStr Exposure to tris(2,4-di-tert-butylphenyl) phosphate during adolescence induces testicular toxicity in mice: Autophagy-apoptosis interplay
title_full_unstemmed Exposure to tris(2,4-di-tert-butylphenyl) phosphate during adolescence induces testicular toxicity in mice: Autophagy-apoptosis interplay
title_short Exposure to tris(2,4-di-tert-butylphenyl) phosphate during adolescence induces testicular toxicity in mice: Autophagy-apoptosis interplay
title_sort exposure to tris 2 4 di tert butylphenyl phosphate during adolescence induces testicular toxicity in mice autophagy apoptosis interplay
topic Tris(2
4-di-tert-butylphenyl) phosphate
Adolescent exposure
Testicular toxicity
Autophagy
Apoptosis
url http://www.sciencedirect.com/science/article/pii/S0147651325009431
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