Tetrabromobisphenol S (TBBPS) exposure induced the testicular aging through NLRP3-mediated inflammatory signaling pathway in vitro and in vivo

IF 4.8 2区 医学 Q2 IMMUNOLOGY International immunopharmacology Pub Date : 2025-03-16 DOI:10.1016/j.intimp.2025.114476
Yuebing Kong , Deyi Wu , Guoxia Wang , Meng Zhang , Ruoting Zhang , Haochu Deng , Jiawen Li , Hainan Lan
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Abstract

Tetrabromobisphenol A (TBBPA) is an extensively employed Brominated flame retardant (BFR), but studies have shown that it has a range of toxicities, and it has been banned from use at present. Tetrabromobisphenol S (TBBPS) is increasingly used in industrial production as a substitute for TBBPA. However, up to now, the toxicity and molecular mechanism of TBBPS in the reproductive system have not been fully revealed. Therefore, we investigated the effects of TBBPS on testicular. In vitro, GC-1 cells and TM4 cells were used as models to perform an array of biochemical tests, and the toxicological impacts of TBBPS on testicular cells were evaluated. It was found that TBBPS could induce testicular cells senescence. Additionally, p16, p21, and p53 expression were also increased after TBBPS treatment. TBBPS also induced oxidative stress and inflammation response. Mechanistic studies have revealed that TBBPS causes mitochondrial damage, which leads to mitochondrial ds-DNA leakage into the cytoplasm, the NLRP3 inflammasome was then activated, in turn leading to inflammatory and senescence responses in testicular cells. In vivo, we found that TBBPS caused testicular tissue aging and inflammatory responses by detecting a series of molecular markers. In summary, the current study demonstrates that TBBPS can induce aging damage and inflammatory responses in testis, and this study lays a foundation for further exploring the reproductive toxicity of TBBPS.
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来源期刊
CiteScore
8.40
自引率
3.60%
发文量
935
审稿时长
53 days
期刊介绍: International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.
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