BP-3 exposure at environmentally relevant concentrations induced male developmental reproductive toxicity via ER/CCL27/ROS pathway in mice

BP-3 is the most widely used ultraviolet absorber, but its toxic effects and mechanisms far from being elucidated. This study evaluated the male developmental reproductive toxicities and mechanism of low-doses of BP-3. The results indicated that BP-3 (2.28 and 228 μg/L) led to a decrease in sperm qu...

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Main Authors: Hong-Mei Li, Yan-Rong Gao, Qing Chang, Xiu-Ying Pei, Jia-He Sun, Yu-Jia Lin, Ya-Nan Tian, Qiang-Wang, Bin Zhao, Heidi Qunhui Xie, Hui-Ming Ma, Hai-Ming Xu
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Ecotoxicology and Environmental Safety
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Online Access:http://www.sciencedirect.com/science/article/pii/S0147651324016324
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author Hong-Mei Li
Yan-Rong Gao
Qing Chang
Xiu-Ying Pei
Jia-He Sun
Yu-Jia Lin
Ya-Nan Tian
Qiang-Wang
Bin Zhao
Heidi Qunhui Xie
Hui-Ming Ma
Hai-Ming Xu
author_facet Hong-Mei Li
Yan-Rong Gao
Qing Chang
Xiu-Ying Pei
Jia-He Sun
Yu-Jia Lin
Ya-Nan Tian
Qiang-Wang
Bin Zhao
Heidi Qunhui Xie
Hui-Ming Ma
Hai-Ming Xu
author_sort Hong-Mei Li
collection DOAJ
description BP-3 is the most widely used ultraviolet absorber, but its toxic effects and mechanisms far from being elucidated. This study evaluated the male developmental reproductive toxicities and mechanism of low-doses of BP-3. The results indicated that BP-3 (2.28 and 228 μg/L) led to a decrease in sperm quantity, quality and testosterone level, impaired blood-testis barrier (BTB) integrity and cytoskeleton, accompanied by aggravated oxidative stress in testes of mice on postnatal day 56 (PND 56). Notably, chemokine CCL27, a driver of oxidative stress, was significantly upregulated induced by BP-3. Similar disrupted effects were detected in testes of mice on PND14, which could be antagonized by ICI 182780 (estrogen receptor antagonist). Mechanistically, BP-3 directly interacted with ER, which boosted CCL27 expression, reactive oxygen species (ROS) accumulation, and BTB and cytoskeleton impairment. In vitro, si-CCL27 and/or ROS scavenger treatment significantly antagonized BP-3-induced oxidative stress and the decrease of BTB and cytoskeleton related genes in TM4 cells. These findings demonstrate that prolonged exposure to low-doses of BP-3 resulted in detrimental effects on testicular development through activation of the ER/CCL27/ROS axis. This study provides a novel perspective understanding the male reproductive toxicity risk caused by BPs exposure at low-doses.
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spelling doaj-art-5310ea164afc43b0b68fecbf2046c48d2025-02-12T05:29:43ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01290117556BP-3 exposure at environmentally relevant concentrations induced male developmental reproductive toxicity via ER/CCL27/ROS pathway in miceHong-Mei Li0Yan-Rong Gao1Qing Chang2Xiu-Ying Pei3Jia-He Sun4Yu-Jia Lin5Ya-Nan Tian6 Qiang-Wang7Bin Zhao8Heidi Qunhui Xie9Hui-Ming Ma10Hai-Ming Xu11The Key Laboratory of Fertility Preservation and Maintenance of the Ministry of Education, Ningxia Medical University, Yinchuan, Ningxia 750004, China; School of Basic Medicine, Ningxia Medical University, Yinchuan, Ningxia 750004, China; School of Public Health, Ningxia Medical University, Yinchuan, Ningxia 750004, ChinaThe Key Laboratory of Fertility Preservation and Maintenance of the Ministry of Education, Ningxia Medical University, Yinchuan, Ningxia 750004, China; School of Basic Medicine, Ningxia Medical University, Yinchuan, Ningxia 750004, China; School of Public Health, Ningxia Medical University, Yinchuan, Ningxia 750004, ChinaThe Key Laboratory of Fertility Preservation and Maintenance of the Ministry of Education, Ningxia Medical University, Yinchuan, Ningxia 750004, China; School of Basic Medicine, Ningxia Medical University, Yinchuan, Ningxia 750004, ChinaThe Key Laboratory of Fertility Preservation and Maintenance of the Ministry of Education, Ningxia Medical University, Yinchuan, Ningxia 750004, China; School of Basic Medicine, Ningxia Medical University, Yinchuan, Ningxia 750004, ChinaThe Key Laboratory of Fertility Preservation and Maintenance of the Ministry of Education, Ningxia Medical University, Yinchuan, Ningxia 750004, China; School of Basic Medicine, Ningxia Medical University, Yinchuan, Ningxia 750004, ChinaSchool of Public Health, Ningxia Medical University, Yinchuan, Ningxia 750004, China; The Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, Yinchuan, Ningxia 750004, ChinaThe Key Laboratory of Fertility Preservation and Maintenance of the Ministry of Education, Ningxia Medical University, Yinchuan, Ningxia 750004, China; School of Basic Medicine, Ningxia Medical University, Yinchuan, Ningxia 750004, ChinaMedical Science and Technology Research Center, Yinchuan, Ningxia 750004, ChinaState Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, ChinaState Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; Corresponding author.The Key Laboratory of Fertility Preservation and Maintenance of the Ministry of Education, Ningxia Medical University, Yinchuan, Ningxia 750004, China; School of Basic Medicine, Ningxia Medical University, Yinchuan, Ningxia 750004, China; Corresponding authors at: The Key Laboratory of Fertility Preservation and Maintenance of the Ministry of Education, Ningxia Medical University, Yinchuan, Ningxia 750004, China.The Key Laboratory of Fertility Preservation and Maintenance of the Ministry of Education, Ningxia Medical University, Yinchuan, Ningxia 750004, China; School of Public Health, Ningxia Medical University, Yinchuan, Ningxia 750004, China; The Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, Yinchuan, Ningxia 750004, China; Corresponding authors at: The Key Laboratory of Fertility Preservation and Maintenance of the Ministry of Education, Ningxia Medical University, Yinchuan, Ningxia 750004, China.BP-3 is the most widely used ultraviolet absorber, but its toxic effects and mechanisms far from being elucidated. This study evaluated the male developmental reproductive toxicities and mechanism of low-doses of BP-3. The results indicated that BP-3 (2.28 and 228 μg/L) led to a decrease in sperm quantity, quality and testosterone level, impaired blood-testis barrier (BTB) integrity and cytoskeleton, accompanied by aggravated oxidative stress in testes of mice on postnatal day 56 (PND 56). Notably, chemokine CCL27, a driver of oxidative stress, was significantly upregulated induced by BP-3. Similar disrupted effects were detected in testes of mice on PND14, which could be antagonized by ICI 182780 (estrogen receptor antagonist). Mechanistically, BP-3 directly interacted with ER, which boosted CCL27 expression, reactive oxygen species (ROS) accumulation, and BTB and cytoskeleton impairment. In vitro, si-CCL27 and/or ROS scavenger treatment significantly antagonized BP-3-induced oxidative stress and the decrease of BTB and cytoskeleton related genes in TM4 cells. These findings demonstrate that prolonged exposure to low-doses of BP-3 resulted in detrimental effects on testicular development through activation of the ER/CCL27/ROS axis. This study provides a novel perspective understanding the male reproductive toxicity risk caused by BPs exposure at low-doses.http://www.sciencedirect.com/science/article/pii/S0147651324016324Benzophenone-3 (BP-3)Male reproductive toxicityBlood-testis barrierCytoskeletonEnvironmentally relevant concentrations
spellingShingle Hong-Mei Li
Yan-Rong Gao
Qing Chang
Xiu-Ying Pei
Jia-He Sun
Yu-Jia Lin
Ya-Nan Tian
Qiang-Wang
Bin Zhao
Heidi Qunhui Xie
Hui-Ming Ma
Hai-Ming Xu
BP-3 exposure at environmentally relevant concentrations induced male developmental reproductive toxicity via ER/CCL27/ROS pathway in mice
Ecotoxicology and Environmental Safety
Benzophenone-3 (BP-3)
Male reproductive toxicity
Blood-testis barrier
Cytoskeleton
Environmentally relevant concentrations
title BP-3 exposure at environmentally relevant concentrations induced male developmental reproductive toxicity via ER/CCL27/ROS pathway in mice
title_full BP-3 exposure at environmentally relevant concentrations induced male developmental reproductive toxicity via ER/CCL27/ROS pathway in mice
title_fullStr BP-3 exposure at environmentally relevant concentrations induced male developmental reproductive toxicity via ER/CCL27/ROS pathway in mice
title_full_unstemmed BP-3 exposure at environmentally relevant concentrations induced male developmental reproductive toxicity via ER/CCL27/ROS pathway in mice
title_short BP-3 exposure at environmentally relevant concentrations induced male developmental reproductive toxicity via ER/CCL27/ROS pathway in mice
title_sort bp 3 exposure at environmentally relevant concentrations induced male developmental reproductive toxicity via er ccl27 ros pathway in mice
topic Benzophenone-3 (BP-3)
Male reproductive toxicity
Blood-testis barrier
Cytoskeleton
Environmentally relevant concentrations
url http://www.sciencedirect.com/science/article/pii/S0147651324016324
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