p-phenoxyphenol impaired male fertility by disrupting the testicular function and local microenvironment

p-phenoxyphenol (PhOP) is an endocrine-disrupting chemical commonly used as an industrial raw material. It can be released either as a monomer or as a metabolite from products containing PhOP. PhOP has been reported to have estrogenic activity, but its reproductive toxicity effect on males remains u...

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Main Authors: Xiaojuan Han, Danni Jiang, Qianni Li, Pengfei Li, Lan Chao, Yang Yang
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Ecotoxicology and Environmental Safety
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Online Access:http://www.sciencedirect.com/science/article/pii/S0147651325007766
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author Xiaojuan Han
Danni Jiang
Qianni Li
Pengfei Li
Lan Chao
Yang Yang
author_facet Xiaojuan Han
Danni Jiang
Qianni Li
Pengfei Li
Lan Chao
Yang Yang
author_sort Xiaojuan Han
collection DOAJ
description p-phenoxyphenol (PhOP) is an endocrine-disrupting chemical commonly used as an industrial raw material. It can be released either as a monomer or as a metabolite from products containing PhOP. PhOP has been reported to have estrogenic activity, but its reproductive toxicity effect on males remains unclear. In this study, a PhOP exposure model was constructed by gavage of 3, 30, and 100 mg/kg/d PhOP into ICR mice for 6 weeks. PhOP exposure decreased sperm motility and damaged testicular structure in mice. Oral exposure to PhOP notably inhibited cell proliferation, promoted cell apoptosis, and elevated oxidative stress levels in mice testis. Additionally, PhOP disrupts steroidogenesis and compromises the blood-testis barrier integrity. To assess its reproductive toxicity in vitro, we exposed GC-2, TM3, and TM4 cells to 0, 10, 20, and 40 μM PhOP for 24 hours. The findings revealed that PhOP reduced proliferation and triggered apoptosis and oxidative stress in GC-2 cells. In TM3 cells, PhOP exposure led to apoptosis and altered the expression of genes related to testosterone synthesis. Similarly, in TM4 cells, PhOP promoted apoptosis and disrupted the expression of genes associated with the blood-testis barrier. Finally, our study confirmed that PhOP significantly reduced sperm motility in human semen samples. In conclusion, PhOP induced male reproductive toxicity by their multifaceted toxicity on testis and sperm in mice, providing novel insights into the reproductive risks of PhOP to mammals.
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spelling doaj-art-eb6efa2aa7554d29aaa49a4e94cbfad62025-08-20T02:06:19ZengElsevierEcotoxicology and Environmental Safety0147-65132025-07-0130011843610.1016/j.ecoenv.2025.118436p-phenoxyphenol impaired male fertility by disrupting the testicular function and local microenvironmentXiaojuan Han0Danni Jiang1Qianni Li2Pengfei Li3Lan Chao4Yang Yang5Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Ji'nan, Shandong 250012, China; Shandong Key Laboratory of Reproductive Health and Birth Defects Prevention and Control, Ji'nan, Shandong 250012, ChinaCenter for Reproductive Medicine, Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Ji'nan, Shandong 250012, China; Shandong Key Laboratory of Reproductive Health and Birth Defects Prevention and Control, Ji'nan, Shandong 250012, ChinaCenter for Reproductive Medicine, Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Ji'nan, Shandong 250012, China; Shandong Key Laboratory of Reproductive Health and Birth Defects Prevention and Control, Ji'nan, Shandong 250012, ChinaCenter for Reproductive Medicine, Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Ji'nan, Shandong 250012, China; Shandong Key Laboratory of Reproductive Health and Birth Defects Prevention and Control, Ji'nan, Shandong 250012, ChinaCenter for Reproductive Medicine, Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Ji'nan, Shandong 250012, China; Shandong Key Laboratory of Reproductive Health and Birth Defects Prevention and Control, Ji'nan, Shandong 250012, ChinaCenter for Reproductive Medicine, Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Ji'nan, Shandong 250012, China; Shandong Key Laboratory of Reproductive Health and Birth Defects Prevention and Control, Ji'nan, Shandong 250012, China; Corresponding author at: Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Ji'nan, Shandong 250012, Chinap-phenoxyphenol (PhOP) is an endocrine-disrupting chemical commonly used as an industrial raw material. It can be released either as a monomer or as a metabolite from products containing PhOP. PhOP has been reported to have estrogenic activity, but its reproductive toxicity effect on males remains unclear. In this study, a PhOP exposure model was constructed by gavage of 3, 30, and 100 mg/kg/d PhOP into ICR mice for 6 weeks. PhOP exposure decreased sperm motility and damaged testicular structure in mice. Oral exposure to PhOP notably inhibited cell proliferation, promoted cell apoptosis, and elevated oxidative stress levels in mice testis. Additionally, PhOP disrupts steroidogenesis and compromises the blood-testis barrier integrity. To assess its reproductive toxicity in vitro, we exposed GC-2, TM3, and TM4 cells to 0, 10, 20, and 40 μM PhOP for 24 hours. The findings revealed that PhOP reduced proliferation and triggered apoptosis and oxidative stress in GC-2 cells. In TM3 cells, PhOP exposure led to apoptosis and altered the expression of genes related to testosterone synthesis. Similarly, in TM4 cells, PhOP promoted apoptosis and disrupted the expression of genes associated with the blood-testis barrier. Finally, our study confirmed that PhOP significantly reduced sperm motility in human semen samples. In conclusion, PhOP induced male reproductive toxicity by their multifaceted toxicity on testis and sperm in mice, providing novel insights into the reproductive risks of PhOP to mammals.http://www.sciencedirect.com/science/article/pii/S0147651325007766p-phenoxyphenolMale fertilityTesticular microenvironmentSpermatogenesisSperm qualityBlood-testis barrier
spellingShingle Xiaojuan Han
Danni Jiang
Qianni Li
Pengfei Li
Lan Chao
Yang Yang
p-phenoxyphenol impaired male fertility by disrupting the testicular function and local microenvironment
Ecotoxicology and Environmental Safety
p-phenoxyphenol
Male fertility
Testicular microenvironment
Spermatogenesis
Sperm quality
Blood-testis barrier
title p-phenoxyphenol impaired male fertility by disrupting the testicular function and local microenvironment
title_full p-phenoxyphenol impaired male fertility by disrupting the testicular function and local microenvironment
title_fullStr p-phenoxyphenol impaired male fertility by disrupting the testicular function and local microenvironment
title_full_unstemmed p-phenoxyphenol impaired male fertility by disrupting the testicular function and local microenvironment
title_short p-phenoxyphenol impaired male fertility by disrupting the testicular function and local microenvironment
title_sort p phenoxyphenol impaired male fertility by disrupting the testicular function and local microenvironment
topic p-phenoxyphenol
Male fertility
Testicular microenvironment
Spermatogenesis
Sperm quality
Blood-testis barrier
url http://www.sciencedirect.com/science/article/pii/S0147651325007766
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