Yttrium nitrate activates the oxidative stress-mediated NF-κB pathway to induce testicular inflammatory response and reduce sperm quality in mice

The rising environmental levels of yttrium have sparked concerns regarding its possible health hazards. Nevertheless, limited toxicological data are available to determine yttrium's toxicity and potential mechanisms on sperm. In our research, the action of oxidative stress and the NF-κB pathway...

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Main Authors: Si-Fan Zhang, Na Li, Dong-Li Liu, Yong-Hong Li, Yi Yang, Yao Ma, Yu-Qing Wang, Yue Ma, Zhao-jin Luan
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/S0147651325010656
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author Si-Fan Zhang
Na Li
Dong-Li Liu
Yong-Hong Li
Yi Yang
Yao Ma
Yu-Qing Wang
Yue Ma
Zhao-jin Luan
author_facet Si-Fan Zhang
Na Li
Dong-Li Liu
Yong-Hong Li
Yi Yang
Yao Ma
Yu-Qing Wang
Yue Ma
Zhao-jin Luan
author_sort Si-Fan Zhang
collection DOAJ
description The rising environmental levels of yttrium have sparked concerns regarding its possible health hazards. Nevertheless, limited toxicological data are available to determine yttrium's toxicity and potential mechanisms on sperm. In our research, the action of oxidative stress and the NF-κB pathway on decreased sperm quality and testicular inflammatory reaction induced by yttrium exposure was analyzed. Yttrium nitrate (YN), N-Acetyl Cysteine (NAC), and JSH-23 were used to intervene in mice and cells in vivo and in vitro experiments. Eosin-nigrosine staining, in vitro fertilization, Annexin V-FITC/PI staining, ICP-MS, Hematoxylin-eosin staining, RT-qPCR, DCFH-DA staining, biochemical methods, ELISA, and western blot were applied to detect sperm motility, fertilizing capacity, apoptosis, Y3+ accumulation, testicular structure, testicular function, and NF-κB gene expression, ROS, MDA, GSH, pro-inflammatory cytokines, and NF-κB protein expression, respectively. The results revealed that YN exposure reduced sperm motility, increased sperm apoptosis, disrupted testicular tissue structure and function in mice. Exposure to YN increased ROS content and NF-κB pathway activation in testicular tissue and cells, resulting in upregulation of pro-inflammatory cytokines in the testis. When NAC scavenged ROS, the YN-induced sperm damage and inflammatory reaction, and NF-κB pathway abnormal activation in the testis of mice were alleviated. In addition, sperm damage and testicular inflammatory reaction caused by YN were alleviated after blocking the NF-κB pathway with JSH-23 treatment. Our present study elucidated that YN could damage sperm quality and induce testicular inflammatory reaction, establishing YN's toxicological impact on the male reproductive system.
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spelling doaj-art-c0e5efb3da1e4e2db070138d91746e262025-08-20T03:05:34ZengElsevierEcotoxicology and Environmental Safety0147-65132025-09-0130211872010.1016/j.ecoenv.2025.118720Yttrium nitrate activates the oxidative stress-mediated NF-κB pathway to induce testicular inflammatory response and reduce sperm quality in miceSi-Fan Zhang0Na Li1Dong-Li Liu2Yong-Hong Li3Yi Yang4Yao Ma5Yu-Qing Wang6Yue Ma7Zhao-jin Luan8School of Basic Medicine and Forensic Medicine, Baotou Medical College, Baotou, Inner Mongolia 014040, People's Republic of ChinaSchool of Basic Medicine, Jinzhou Medical University, Jinzhou, Liaoning 121001, People's Republic of ChinaSchool of Basic Medicine and Forensic Medicine, Baotou Medical College, Baotou, Inner Mongolia 014040, People's Republic of ChinaSchool of Basic Medicine and Forensic Medicine, Baotou Medical College, Baotou, Inner Mongolia 014040, People's Republic of ChinaSchool of Basic Medicine and Forensic Medicine, Baotou Medical College, Baotou, Inner Mongolia 014040, People's Republic of ChinaSchool of Basic Medicine and Forensic Medicine, Baotou Medical College, Baotou, Inner Mongolia 014040, People's Republic of ChinaSchool of Basic Medicine and Forensic Medicine, Baotou Medical College, Baotou, Inner Mongolia 014040, People's Republic of ChinaSchool of Basic Medicine and Forensic Medicine, Baotou Medical College, Baotou, Inner Mongolia 014040, People's Republic of ChinaSchool of Basic Medicine and Forensic Medicine, Baotou Medical College, Baotou, Inner Mongolia 014040, People's Republic of China; Corresponding author.The rising environmental levels of yttrium have sparked concerns regarding its possible health hazards. Nevertheless, limited toxicological data are available to determine yttrium's toxicity and potential mechanisms on sperm. In our research, the action of oxidative stress and the NF-κB pathway on decreased sperm quality and testicular inflammatory reaction induced by yttrium exposure was analyzed. Yttrium nitrate (YN), N-Acetyl Cysteine (NAC), and JSH-23 were used to intervene in mice and cells in vivo and in vitro experiments. Eosin-nigrosine staining, in vitro fertilization, Annexin V-FITC/PI staining, ICP-MS, Hematoxylin-eosin staining, RT-qPCR, DCFH-DA staining, biochemical methods, ELISA, and western blot were applied to detect sperm motility, fertilizing capacity, apoptosis, Y3+ accumulation, testicular structure, testicular function, and NF-κB gene expression, ROS, MDA, GSH, pro-inflammatory cytokines, and NF-κB protein expression, respectively. The results revealed that YN exposure reduced sperm motility, increased sperm apoptosis, disrupted testicular tissue structure and function in mice. Exposure to YN increased ROS content and NF-κB pathway activation in testicular tissue and cells, resulting in upregulation of pro-inflammatory cytokines in the testis. When NAC scavenged ROS, the YN-induced sperm damage and inflammatory reaction, and NF-κB pathway abnormal activation in the testis of mice were alleviated. In addition, sperm damage and testicular inflammatory reaction caused by YN were alleviated after blocking the NF-κB pathway with JSH-23 treatment. Our present study elucidated that YN could damage sperm quality and induce testicular inflammatory reaction, establishing YN's toxicological impact on the male reproductive system.http://www.sciencedirect.com/science/article/pii/S0147651325010656Yttrium nitrateTestisSperm motilityOxidative stressNF-κB pathway
spellingShingle Si-Fan Zhang
Na Li
Dong-Li Liu
Yong-Hong Li
Yi Yang
Yao Ma
Yu-Qing Wang
Yue Ma
Zhao-jin Luan
Yttrium nitrate activates the oxidative stress-mediated NF-κB pathway to induce testicular inflammatory response and reduce sperm quality in mice
Ecotoxicology and Environmental Safety
Yttrium nitrate
Testis
Sperm motility
Oxidative stress
NF-κB pathway
title Yttrium nitrate activates the oxidative stress-mediated NF-κB pathway to induce testicular inflammatory response and reduce sperm quality in mice
title_full Yttrium nitrate activates the oxidative stress-mediated NF-κB pathway to induce testicular inflammatory response and reduce sperm quality in mice
title_fullStr Yttrium nitrate activates the oxidative stress-mediated NF-κB pathway to induce testicular inflammatory response and reduce sperm quality in mice
title_full_unstemmed Yttrium nitrate activates the oxidative stress-mediated NF-κB pathway to induce testicular inflammatory response and reduce sperm quality in mice
title_short Yttrium nitrate activates the oxidative stress-mediated NF-κB pathway to induce testicular inflammatory response and reduce sperm quality in mice
title_sort yttrium nitrate activates the oxidative stress mediated nf κb pathway to induce testicular inflammatory response and reduce sperm quality in mice
topic Yttrium nitrate
Testis
Sperm motility
Oxidative stress
NF-κB pathway
url http://www.sciencedirect.com/science/article/pii/S0147651325010656
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