2,6-Dichloro-1,4-benzoquinone(2,6-DCBQ), an emerging water disinfection by-product, is widely detected in water resources. However, its potential effects on the reproductive system are largely unknown. Here, we invest...2,6-Dichloro-1,4-benzoquinone(2,6-DCBQ), an emerging water disinfection by-product, is widely detected in water resources. However, its potential effects on the reproductive system are largely unknown. Here, we investigated the long-term effects of 2,6-DCBQ on gonadal development by exposing zebrafish from 15 to 180 days postfertilization(dpf). Following exposure to 2,6-DCBQ(20 and 100 μg/L), female-specific effects including delayed puberty onset, retarded ovarian growth and breakdown of the zona radiata were observed, resulting in subfertility in adult females. Adverse effects in folliculogenesis disappeared two months after cessation of 2,6-DCBQ administration. In contrast, no adverse impacts were noted in male testes. The effects on females were associated with significant reduction in 17 β-estradiol(E2) level, suggesting a role for 2,6-DCBQ in anti-estrogenic activity. E2 level change in blood was further supported by dysregulated expression of genes( cyp19a1a, fshb, kiss3, esr2b, vtg1, and vtg3) related to the hypothalamic-pituitary-gonad-liver(HPGL) axis. The present study demonstrates for the first time that 2,6-DCBQ induces reproductive impairments in female zebrafish through disrupting 17 β-estradiol level.展开更多
Halobenzoquinones(HBQs),a class of water dis-infection byproducts(DBPs),have emerged as potential bladder carcinogens.However,evidence regarding the long-term health effects of HBQexposure and their potential to induc...Halobenzoquinones(HBQs),a class of water dis-infection byproducts(DBPs),have emerged as potential bladder carcinogens.However,evidence regarding the long-term health effects of HBQexposure and their potential to induce malignant trans-formation remains limited.Here,we examined the chronic effects of 2,6-dichlorobenzoquinone(2,6-DCBQ)exposure on human immor-talized uroepithelial cells(SV-HUC-1),with a focus on malignant transformation.Cells were continuously exposed to a noncytotoxic concentration of 2,6-DCBQfor over three months.The long-term transformed cells exhibited cellular and nuclear pleomorphism and anchorage-independent cell growth—a hallmark of cancer cell transformation.Proteomic analysis identified 60 differentially ex-pressed proteins(DEPs),20 of which are strongly associated with specific pathways of urinary bladder and urothelial cells.Enrichment analysis highlighted the actin cytoskeleton and extracellular matrix(ECM)-receptor interaction pathways.These molecular changes were supported by immunofluorescence assay,revealing filamentous actin disorganization and vinculin mislocalization in 2,6-DCBQ-treated cells.Together,these results suggest that cytoskeletal destabilization and adhesion collapse are key features associated with 2,6-DCBQ-induced malignant transformation,indicating that chronic exposure to low-level waterborne HBQs is associated with human bladder carcinogenesis.展开更多
基金supported by Xuzhou Medical University start-up grant for excellent scientists (Nos. RC20552044, RC20552054)the Natural Science Research of the Jiangsu Higher Education Institutions (Nos. 21KJB330007, 21KJB320001)。
文摘2,6-Dichloro-1,4-benzoquinone(2,6-DCBQ), an emerging water disinfection by-product, is widely detected in water resources. However, its potential effects on the reproductive system are largely unknown. Here, we investigated the long-term effects of 2,6-DCBQ on gonadal development by exposing zebrafish from 15 to 180 days postfertilization(dpf). Following exposure to 2,6-DCBQ(20 and 100 μg/L), female-specific effects including delayed puberty onset, retarded ovarian growth and breakdown of the zona radiata were observed, resulting in subfertility in adult females. Adverse effects in folliculogenesis disappeared two months after cessation of 2,6-DCBQ administration. In contrast, no adverse impacts were noted in male testes. The effects on females were associated with significant reduction in 17 β-estradiol(E2) level, suggesting a role for 2,6-DCBQ in anti-estrogenic activity. E2 level change in blood was further supported by dysregulated expression of genes( cyp19a1a, fshb, kiss3, esr2b, vtg1, and vtg3) related to the hypothalamic-pituitary-gonad-liver(HPGL) axis. The present study demonstrates for the first time that 2,6-DCBQ induces reproductive impairments in female zebrafish through disrupting 17 β-estradiol level.
基金supported by grants from Alberta Innovates,the Canada Research Chairs(CRC)Program,and the Natural Sciences and Engineering Research Council of Canada(NSERC).Flow cytometry was performed at the University of Alberta’s Faculty of Medicine and Dentistry Flow Cytometry Facility,with additional support from the Faculty and the Canadian Foundation for Innovation(CFI).C.W.gratefully acknowledges financial support from the China Scholarship Council(CSC).
文摘Halobenzoquinones(HBQs),a class of water dis-infection byproducts(DBPs),have emerged as potential bladder carcinogens.However,evidence regarding the long-term health effects of HBQexposure and their potential to induce malignant trans-formation remains limited.Here,we examined the chronic effects of 2,6-dichlorobenzoquinone(2,6-DCBQ)exposure on human immor-talized uroepithelial cells(SV-HUC-1),with a focus on malignant transformation.Cells were continuously exposed to a noncytotoxic concentration of 2,6-DCBQfor over three months.The long-term transformed cells exhibited cellular and nuclear pleomorphism and anchorage-independent cell growth—a hallmark of cancer cell transformation.Proteomic analysis identified 60 differentially ex-pressed proteins(DEPs),20 of which are strongly associated with specific pathways of urinary bladder and urothelial cells.Enrichment analysis highlighted the actin cytoskeleton and extracellular matrix(ECM)-receptor interaction pathways.These molecular changes were supported by immunofluorescence assay,revealing filamentous actin disorganization and vinculin mislocalization in 2,6-DCBQ-treated cells.Together,these results suggest that cytoskeletal destabilization and adhesion collapse are key features associated with 2,6-DCBQ-induced malignant transformation,indicating that chronic exposure to low-level waterborne HBQs is associated with human bladder carcinogenesis.
