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

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
Subjects:
Benzophenone-3 (BP-3)
Male reproductive toxicity
Blood-testis barrier
Cytoskeleton
Environmentally relevant concentrations
Online Access:http://www.sciencedirect.com/science/article/pii/S0147651324016324
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Summary: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.
ISSN:0147-6513

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