ENVIRONMENTAL POLLUTION
·
2021
·
IF 8.071
Jiajing Xin,Saihong Yan,Xiangsheng Hong,Huan Zhang,Jinmiao Zha
Clozapine (CLZ) is a neuroactive pharmaceutical that is frequently detected in aquatic environments. Although the cardiotoxicity, developmental toxicity, and neurotoxicity of CLZ in aquatic non-target organisms have been reported, its lipotoxicity and underlying mechanism are unknown. Therefore, in this study, 2-month-old Chinese rare minnows were exposed to 0, 0.1, 1, and 10 μg/L CLZ for 90 days. Overt dyslipidemia was observed after CLZ exposure, whereas the body weights of females significantly increased after CLZ exposure (p < 0.05). In addition, obvious hepatocyte vacuolization and hepatic lipid droplet accumulation were observed at all treatment groups (p < 0.05). The activities of sterol regulatory element binding proteins 1 (SREBP1) and fatty acid synthase (FAS) were significantly upregulated at the 1 and 10 μg/L CLZ treatment groups (p < 0.05). Moreover, evident cell boundary disintegration of the intestinal villi and increasing mucus secretion were observed at all treatment groups (p < 0.05). Furthermore, the diversity of the gut microbiota increased, whereas the relative abundances of Proteobacteria , Firmicutes and Bacteroidetes significantly increased after CLZ exposure (p < 0.05). Furthermore, significantly increased bacterial secondary bile acid biosynthesis activity in Chinese rare minnows was observed after 1 μg/L CLZ exposure (p < 0.05). Therefore, our findings confirmed that CLZ induced lipotoxicity by stimulating SREBP1 and affecting the bacterial secondary bile acid biosynthesis activity in Chinese rare minnows.
研究领域:
环境科学
·
毒理学
·
水生生物学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Environmental Sciences
·
2024
·
IF 5.9
Long Zhu,Shangjie Zhou,Li Huang,Xiaotian Wang,Yutong Huang,Jiachen Yu,Zaizhao Wang
Bisphenol A (BPA) is a recognized estrogenic endocrine disruptor that poses a threat to the reproductive health of fish. However, it remains unclear whether and how paternal BPA exposure can lead to developmental toxicity in offspring. To explore the potential paternal BPA exposure impacts on craniofacial cartilage growth in offspring, male rare minnows were subjected to BPA and subsequently mated with normal females to produce progeny. Our results demonstrated that paternal BPA exposure resulted in increased malformation and delayed craniofacial cartilage development in the F1 offspring. Furthermore, BPA exposure led to differential expression of 28 miRNAs in paternal sperm in F0 generation (13 upregulated and 15 downregulated), among which 7 miRNAs were involved in the regulation of bone development. BPA also downregulated the expression of bmp2a and Runx1 during F1 embryonic development. The inhibited bmp2a expression might derive from BPA's stimulation of one miRNA, aca-miR-16a-5P, due to bmp2a being one of its target genes. Notably, paternal BPA exposure did not affect craniofacial cartilage development or gonadal development in the F2 generation. Overall, our study sheds light on the molecular mechanisms underlying the impact of paternal BPA exposure on facial chondrogenesis in offspring and provides theoretical support for the ecological protection of fish populations.
研究领域:
环境毒理学
·
发育生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AQUATIC TOXICOLOGY
·
2025
·
IF 4.3
Hongbo Yang,Chan Xu,Jieyu Song,Jin Li,Chan Zhang,Chunli Teng,Kai Ma,Feng Xie
Perfluorooctane sulfonic acid (PFOS) and its alternative 6:2 chlorinated polyfluoroethersulfonate (6:2 Cl-PFESA, also known as F-53B), are frequently detected in a variety of environmental and human samples. These substances have been associated with hepatotoxic effects, including disorders in lipid metabolism and oxidative stress. However, the molecular mechanisms underlying the causal relationship between exposure to F-53B and hepatotoxicity remain inadequately understood. This study investigated the toxicokinetics and mechanisms of hepatotoxicity associated with prolonged exposure to F-53B in adult Chinese rare minnows. Specifically, 5-month-old adult Chinese rare minnow was exposed to concentrations of 10 μg/L and 200 μg/L of F-53B for a duration of 28 days for bioaccumulation assessment, followed by a 14-day period for metabolic evaluation. The findings indicated that the bioaccumulation of F-53B in the tissues was positively correlated with the exposure concentrations. The logarithmic bioconcentration factor (Log BCF28d) was determined to be 2.67 ± 0.02 for the low concentration group and 2.27 ± 0.01 for the high concentration group. The calculated half-lives (t 1/2 ) were 18.50 ± 1.67 days and 21.38 ± 0.31 days for the respective concentration groups. F-53B protein exhibited a distinct tissue-specific distribution in adult Chinese rare minnow, with the following order of enrichment: Blood > Liver > Gonad > Gill > Intestine > Brain > Muscle. F-53B was primarily concentrated in the blood and liver, where the protein content was significantly higher. Exposure to F-53B for 28 days significantly elevated biochemical levels associated with lipid metabolism and increased the activities of the enzymes FAS, PPARα, and ACC in the liver. This exposure also resulted in impairment of the hepatic oxidative system in the Chinese rare minnow, with F-53B significantly reducing most of the measured markers related to oxidative stress (e.g., GSH, SOD, CAT, and MDA). Proteomic analysis indicated that the toxicity of F-53B regulates the expression of proteins across several functional classes. Based on the functional information of the differential proteins provided in UniProt and KEGG, they were categorized into five main categories: Cellular Processes, Environmental Information Processing, Genetic Information Processing, Metabolism, and Organismal Systems. This study indicate that F-53B is bioaccumulative and persistent in Chinese rare minnow, and can further induce oxidative stress and lipid metabolism disorders. Combined with proteomic research methods, the toxicological effects of F-53B on Chinese rare minnow can be better explained.
研究领域:
生态毒理学
·
蛋白质组学
·
环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2019
·
IF 4.527
Cong Yuan,Lihong Wang,Long Zhu,Benhui Ran,Xue Xue,Zaizhao Wang
Ubiquitous BPA exposure resulted in DNA methylation errors and oxidative stress . Numerous studies have demonstrated that oxidative stress can lead to changes in DNA methylation levels and supplementation with antioxidants, including N-acetylcysteine (NAC), was able to restore these changes. Our previous study supposed that BPA-induced de novo synthesis of glutathione (GSH) promoted DNA methylation process in Gobiocypris rarus testes . To validate this conjecture and explore the protective effects of NAC on BPA toxicity, the present study was carried out. Adult male G. rarus was treated with 225 μg L −1 BPA and/or NAC for 7 days. The sperm motility and DNA integrity of G. rarus were determined. Meanwhile, the levels of 5-methylcytosine (5mC), GSH, hydrogen peroxide (H 2 O 2 ), DNA methyltransferase proteins (DNMTs), γ-glutamyl cysteine synthetase (GCS), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), homocysteine (HCY), nicotinamide adenine dinucleotide phosphate (NADPH) and cysteine in the testes were detected. Furthermore, the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were measured. Results indicated that NAC addition resulted in increase of cysteine contents and partially inhibited the BPA-induced DNA hypermethylation of G. rarus testes. In addition, the changes in DNA methylation levels in the testes after BPA and/or NAC treatment might be controlled by DNA methylation process that mediated by DNMTs. Moreover, BPA exposure caused oxidative stress in the testes and the elimination of H 2 O 2 might be mainly accomplished by CAT while it changed to mainly through GPx after NAC supplement. Finally, the positive response of testicular antioxidant enzyme system and the antioxidant activity of NAC itself protected sperm motility and DNA integrity from oxidative damage in each group.
研究领域:
环境科学
·
毒理学
·
分子生物学
·
水生生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AQUATIC TOXICOLOGY
·
2022
·
IF 5.202
Long Zhu,Yongjing Guan,Xuening Li,Xiaofan Xiong,Jialin Liu,Zaizhao Wang
Bisphenol-A (BPA) has been reported to disrupt blood-testis barrier (BTB) integrity in mammals. However, its effects on fish testis sertoli cell (SC) barrier and the underlying mechanisms have been largely unknown to date. To study the SC barrier toxicity induced by BPA, male rare minnows ( Gobiocypris rarus ) were exposed to 15 μg L − 1 BPA for 7, 14 and 21 d. Meanwhile, a 25 ng L −1 17α-ethynyl estradiol (EE2) group was set up as the positive control. Results showed that BPA induced immune response in the testes and decreased offspring hatching rate. The biotin tracer assay showed that BPA exposure destroyed the integrity of the testis SC barrier. In addition, BPA exposure decreased the expressions of occludin, ZO-1, CX43 and N-cadherin proteins. The transcripts of CX43 and occludin were significantly decreased and SP1 recruitment in each gene promoter was repressed after BPA exposure. Moreover, the cytokines (TNFα and IL-1β) were significantly increased while the JNK signal pathway was activated after BPA exposure. BPA also increased the matrix metalloproteinases 1 (MMP1) and MMP2 levels in the testes. In addition, estrogenic effect did not entirely explain the mechanism by which BPA disrupted the SC barrier in G. rarus testes. These results suggested that BPA disrupted the SC barrier integrity by inhibiting SP1 enrichments within CX43 and occludin 5′ flanking regions through activated cytokines/JNK signaling pathway. MMPs were also involved in the disruption of SC barrier caused by BPA exposure.
研究领域:
环境毒理学
·
生殖生物学
·
水生毒理学
✓ 已验证
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2026
·
IF 6.6
Yuyang Ma,Xiaotian Wang,Huan He,Xiangxuan Wang,Xinbin Zhang,Long Zhu,Shiqi Fan,Yufeng Shen,Chengke Zhu
Microplastics and pesticides often coexist in freshwater environments; however, their combined effects on teleost branchial tissues remain unclear. In this study, adult Gobiocypris rarus were exposed to polystyrene microplastics (PS-MPs, 1 mg/L), permethrin (PM, 0.5 μg/L), or their combination for 21 days. Gill toxicity was evaluated using histopathology, scanning electron microscopy, biochemical assays, immunofluorescence staining, transcriptomics, and 16S rRNA sequencing. Our results revealed that both single and co-exposure manifested as sublethal toxicity in gill tissues, with co-exposure generally inducing more pronounced and widespread adverse effects. Histological and ultrastructural observations showed that co-exposure exacerbated lamellar deformation, epithelial vacuolation, microridge disruption, and epithelial surface damage. 8-OHdG staining revealed the most severe oxidative DNA damage in the PM group. Biochemical analyses showed decreased superoxide dismutase (SOD) activity in all exposure groups and increased malondialdehyde (MDA) levels in PM-containing groups. TUNEL analysis showed the most intense apoptotic signal in the co-exposure group. Transcriptomic analysis revealed that co-exposure induced the largest number of differentially expressed genes and mainly affected lipid transport, membrane-related metabolism, programmed cell death, immune regulation, and PPAR signaling. In addition, 16S rRNA sequencing showed that co-exposure disrupted the gill-associated microbiota, with a loss of dominant commensal bacteria and an increase in opportunistic taxa. Combined analysis further showed that microbial changes were closely associated with oxidative injury, apoptosis-related responses, and immune-related indicators. Overall, these findings indicate that PS-MPs and PM co-exposure exacerbates gill toxicity through multi-level injury processes, providing a theoretical basis for evaluating the ecological risks of microplastic–pesticide co-contamination in freshwater fish.
✓ 已验证
DOI
高影响因子
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
·
2022
·
IF 4.52
Long Zhu,Mingrong Wang,Shuo Fu,Kaiqi Li,Jialin Liu,Zaizhao Wang
Bisphenol A (BPA) is a widely used endocrine disruptor , which has attracted much attention due to its harmful effects on male reproduction. To investigate the interference of BPA on steroid synthesis in males, male rare minnows ( Gobiocypris rarus ) were exposed to 15 μg L −1 BPA for 7, 14 and 21 d. Meanwhile, a positive control group was performed with 25 ng L −1 17α-ethynyl estradiol (EE2). Results showed that BPA exposure induced lower testosterone (T) levels, while affecting the transcripts of steroidogenic gene StAR . Moreover, BPA induced abnormal germ cells proliferation in the testis in rare minnow. Transcriptome analysis showed that 354 transcripts significantly differentially expressed after BPA exposure for 14 d, several of them were enriched in the signaling pathways of cell cycle process, PPAR signaling pathway, the steroid synthesis pathway and estrogen signaling pathway. BPA significantly increased estrogen receptor (ER) levels and induced abnormal protein levels of PPARγ. BPA disrupted the StAR expression by interfering ER enrichments within StAR 5′ flanking region . Additionally, our study also revealed that BPA and EE2 might have different mechanisms for interfering with steroid hormone levels and germ cells proliferation in the testis.
研究领域:
环境科学
·
内分泌学
·
分子生物学
·
生殖生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2026
·
IF 6.6
Yuehui Zhao,Ya Zhao,Junshuai Lv,Hailin Gong,Hui Yang
Nitrite (NO₂⁻) is a common nitrogenous contaminant in aquatic environments and drinking water, but its mechanisms of action on male reproduction are still not fully understood. In this study, male rare minnow ( Gobiocypris rarus ) were used as a model to investigate the effects of chronic NO₂⁻ exposure on testicular structure, energy metabolism, and sperm quality, and to elucidate the roles of hypoxia-inducible factor-1 ( hif1a ) and its associated metabolic genes. Fish were exposed for 21 days to control water or two environmentally relevant NO₂⁻ concentrations (0.5 and 2 mg/L NO₂⁻-N, respectively). Exposure to NO₂⁻ did not significantly affect body length or body weight, but low-dose NO₂⁻ increased testis weight and gonadosomatic index (GSI). At both doses, testicular histology was disrupted, ATP content decreased, and sperm concentration and motility were reduced, suggesting that the elevated GSI more likely reflects pathological changes in the testes rather than enhanced reproductive function. The rare minnow hif1a encoded a protein containing the typical structural domains of Hif1a, was highly conserved with other vertebrates, and was constitutively expressed in the testis. Early during NO₂⁻ exposure (1 week), testicular hif1a mRNA and protein levels were significantly upregulated, before gradually declining with prolonged exposure and falling below control levels by week 3. Immunofluorescence revealed that NO₂⁻ exposure caused disordered Hif1a distribution and patchy accumulation within the seminiferous epithelium of the testis. A series of genes involved in glucose uptake, glycolysis, lactate transport, and mitochondrial function showed time- and dose-dependent expression changes in the testis, and most of them were positively correlated with hif1a expression. These findings indicate that the “early activation followed by suppression” pattern of Hif1a dynamics is closely associated with testicular energy imbalance under NO₂⁻ exposure. In summary, chronic NO₂⁻ exposure impaired spermatogenesis and sperm motility without significantly affecting somatic growth and was associated with altered testicular hif1a/Hif1a dynamics and transcriptional changes in energy metabolism-related genes. These findings provide new evidence for understanding the reproductive toxicity of environmental nitrite in vertebrates.
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）