JOURNAL OF HAZARDOUS MATERIALS
·
2020
·
IF 9.038
Junke Wang,Tianxin Zhao,Jiadong Chen,Lian Kang,Yuexin Wei,Yuhao Wu,Lindong Han,Lianju Shen,Chunlan Long,Shengde Wu,Guanghui Wei
Di(2-ethylhexyl) phthalate (DEHP) is a widely-used plasticizer and has long been recognized as an endocrine-disrupting chemical with male reproductive toxicities. DEHP exposure at the prepubertal stage may lead to extensive testicular injury. However, the underlying mechanisms remain to be elucidated. In the present study, we gavaged male C57BL/6 mice with different concentrations of DEHP (0, 250, and 500 mg/kg-bw·d) from postnatal day 22–35, and exposed TM3 Leydig cells with 0, 100, 200, 300, and 400 μM of MEHP (bioactive metabolite of DEHP) for 12–48 h. RNA sequencing was performed both in testicular tissue and TM3 cells. The results showed that DEHP disrupts testicular development and reduces serum testosterone levels in male prepubertal mice. Bioinformatic analysis and experimental verification have revealed that DEHP/MEHP induces cell cycle arrest in TM3 cells and increases apoptosis both in vivo and in vitro. Furthermore, the p53 signaling pathway was found to be activated upon DEHP/MEHP treatment. The inhibition of p53 by pifithrin-α significantly reduced MEHP-induced injuries in TM3 cells. Cumulatively, these findings revealed the involvement of the p53 signaling pathway in DEHP-induced prepubertal testicular injury by promoting cell apoptosis and inhibiting cell proliferation of Leydig cells.
研究领域:
毒理学
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生殖生物学
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分子生物学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
Environmental Technology & Innovation
·
2024
·
IF 6.7
Hanjie Zhang,Zhuang Ye,Xiuping Gu,Baowei Hu,Steve A. Wakelin,Guixin Chu
Di-(2-ethylhexyl) phthalate (DEHP) has increasingly accumulated in soils due to DEHP-containing plastic film has been extensively used in agriculture. However, the exposure of DEHP on calcareous soil nitrification potential, ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) are poorly investigated. Here, an incubation experiment was established containing four treatments:(ⅰ) unfertilized blank control, (ⅱ) urea addition alone, (ⅲ) urea plus DEHP (10 mg kg -1 ), (ⅳ) urea plus DEHP (100 mg kg -1 ). The influences of DEHP exposure on soil NH 4 + -N, NO 3 - -N, soil potential nitrification rate (PNR), ammonia monooxygenase (AMO) activity, AOA and AOB were analyzed. We found that DEHP exposure (10 and 100 mg kg -1 ) lowered NO 3 - -N in the treatments of urea plus DEHP 10 and urea plus DEHP 100 , and it significantly decreased soil PNR and AMO activity. Also, the exposure of DEHP reduced the numbers of AOA and AOB gene copies, and decreased AOB community’s α-diversity. Moreover, DEHP exposure destabilized AOB community’s co-occurrence network and decreased key module abundance, but its influences on AOA community was not significant. Taken together, the exposure of DEHP inhibited PNR in a calcareous soil through decreasing AOB gene copies and weakening the co-occurrence network of AOB community. Our findings provide a novel insights into microbial mechanisms about the detrimental effects of DEHP pollution on soil PNR and nitrification process in calcareous soil.
研究领域:
环境科学
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土壤微生物学
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生态毒理学
✓ 已验证
产品关联
DOI
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2022
·
IF 10.753
Xu Shi,Tong Xu,Wei Cui,Xue Qi,Shiwen Xu
Environmental harmful pollutants microplastics (MPs) and di (2-ethyl) hexyl phthalate (DEHP) are widely residual in the environment, which may cause lesion to multiple apparatus by inducing oxidative stress, threatening the health of human and animals. Neutrophil extracellular traps (Nets) are involved in skin wound healing. Most studies focused on the individual effects of different poisons on animals and ecosystems, but there are few studies on the accumulation and interaction of multiple poisons. The purpose of this study is to explore the effect of DEHP and MPs co-exposure on skin wound healing and the formation of Nets. For this purpose, we detected this hypothesis by replicating the DEHP and MPs-exposed skin wound model in mice, as well as the co-culture system of neutrophil and fibroblast. The results displayed that MPs and DEHP exposure delayed skin healing, which was more pronounced in the combined exposure group. In vitro and in vivo experiments confirmed that compared with the DEHP or MPs group, the DEHP+MPs group had more significant oxidative stress, increased Nets release and inflammatory factors, and inhibited the Wnt/β-catenin pathway and fibrosis-related factors. N -acetylcysteine (NAC) attenuated these phenomena. Through the co-culture system, we confirmed that the overproduction of Nets induced fibroblasts to exacerbate inflammatory responses and inhibit Wnt pathway and fibrosis. Overall, DEHP and MPs can produce synergistic toxic injury in mice skin wounds, and the excessive activation of ROS/Nets can aggravate inflammatory and inhibit fibrosis, resulting in delayed wound healing.
研究领域:
环境科学
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毒理学
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细胞生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2022
·
IF 6.78
Xiaofang Zhu,Haowei Fu,Jiahui Sun,Qiannan Di,Qian Xu
Aims Di (2-ethylhexyl) phthalate (DEHP), as an environmental endocrine-disrupting chemical (EDC), can induce male reproductive injury. N6-methyladenosine (m6A) plays a vital role in environmental exposure-induced diseases by regulating gene expression. Therefore, we aim to investigate the role of m6A in DEHP-induced reproductive injury. Main methods We established an in vivo model of mice exposed to DEHP to explore the effect of DEHP on reproductive injury and m6A. To further explore the molecular mechanism of DEHP toxicity, we built a model of GC-2 cells exposed to mono-(2-ethylhexyl) phthalate (MEHP) in vitro and further silenced Mettl3 in GC-2cells. Besides, we also conducted MeRIP-qPCR and RIP assays to identify the target genes for m6A modification. Key findings DEHP induced testicular injury and senescence. And telomeres shortening, reduced levels of telomere repeat–binding factor 1 (TRF1), TRF2, protection of telomeres 1 (POT1), and telomerase reverse transcriptase (TERT) can be observed in DEHP-treated testes. MEHP also induced GC-2 cellular senescence and telomere dysfunction. Besides, increased m6A mediated by METTL3 stabilized homeobox containing 1 ( Hmbox1 ) in an m6A-dependent manner in MEHP-exposed GC-2 cells. Mettl3 knockdown led to lower m6A modification and reduced Hmbox1 stability, resulting in further shortening of telomere length. Significance our work uncovered that DEHP led to male reproductive injury by telomere dysfunction and m6A modified Hmbox1 contributed to maintaining telomere homeostasis in this process, suggesting that accurate regulation of m6A modification level by drugs has potential value in the treatment of DEHP-induced male reproductive injury.
研究领域:
毒理学
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生殖生物学
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分子生物学
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表观遗传学
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产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2023
·
IF 9.8
Yijie Chen,Zhen Zhen,Gaoyang Li,Huijun Li,Ting Wei,Fengcheng Huang,Tao Li,Changhong Yang,Lei Ren,Yanqiu Liang,Zhong Lin,Dayi Zhang
Di-2-ethylhexyl phthalate (DEHP) is a widespread persistent organic pollutant in the environment. As an ultimate barrier preventing pollutant entry into the ocean, mangrove plays an important role in coastal ecosystem. However, little information is known about DEHP degradation in mangrove rhizosphere. In this study, a rhizobox was used to separate four consecutive rhizosphere compartments with distance of 0–2, 2–4, 4–6, and > 6 mm to the rhizoplane of Kandelia obovata and investigate DEHP gradient degradation behavior in rhizosphere. Sediments closer to the rhizoplane exhibited higher DEHP degradation efficiencies (74.4 % in 0–2 mm layer). More precisely, mangrove rhizosphere promoted the benzoic acid pathway and non-selectively accelerated the production of mono(2-ethylhexyl) phthalate, phthalic acid and benzoic acid. Higher sediment organic matter content, lower pH and less humus in rhizosphere benefited DEHP hydrolysis. In addition, rhizosphere significantly increased microbial biomass and activities comparing to bulk sediments. Some bacterial lineages with potential DEHP degradation capability exhibited a distance-dependent pattern that decreased with the distance to the rhizoplane, including Bacillales , Acidothermaceae , Gammaproteobacteria , and Sphingobacteriales . Our findings suggested that mangrove rhizosphere could accelerate DEHP degradation by altering sediment physicochemical properties and microbial composition, showing positive effects on coastal ecosystem services for eliminating phthalate acid ester contamination.
研究领域:
环境科学
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微生物学
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生态学
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污染物降解
✓ 已验证
DOI
PubMed
高影响因子
PLoS One
·
2025
·Vol. 20
·期 7
·e0313233
·
IF 2.6
Muyao Ding,Hongyu Ma,Hui Du,Yinglong Yang,Min Yu,Cong Zhang
DEHP is the most widely used plasticizer in many products. However, growing evidence has indicated that DEHP may induce neurotoxicity. DEHP exposure affects mircoRNAs (miRNAs) expression in brain. A growing body of evidence suggests that nutrients and other bioactive food components prevent neurotoxicity through regulation of miRNA expression. Due to the increasing concern about the risks of DEHP to human health, we explored the neuroprotective effect of Omega-3 fatty acid (Omega-3FA) on subchronic DEHP-induced neurotoxicity in mice, and the potential involved miRNAs and their targets in the protective action of Omega-3FA against DEHP-induced neurotoxicity. Omega-3FA protected against the DEHP-induced impairment of learning and memory and alleviated the thinning of postsynaptic density (PSD) thickness in hippocampal synapses. We observed that there are fourteen up or down regulated miRNAs associated PSD in DEHP exposure which were normalized by Omega-3FA treatment. Protein targets in PSD of these differentially expressed miRNAs were predicted. Furthermore, the expression levels of protein mGluR5, Homer1, and NMDAR2B were carried out via Western blot, for further verifying PSD associated miRNAs’ targets are involved in neuroprotection of Omega-3FA against DEHP. These findings suggested that Omega-3FA protected DEHP-induced impairment of learning and memory as well as synaptic structure alteration in the hippocampus by regulating the expression of PSD associated miRNAs and their targets. Thus, Omega-3FA should be included in diet to prevent or suppress neurotoxicity caused by continuous exposure to DEHP.
研究领域:
神经科学
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毒理学
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营养学
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分子生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
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2022
·
IF 5.572
Yue-Qiang Huang,Yi-Xi Tang,Bai-Hao Qiu,Milton Talukder,Xue-Nan Li,Jin-Long Li
Di-2-ethylhexyl phthalate (DEHP) has been widely used in many fields (agricultural products, medical instruments, and food packing). As an environmental contaminant, DEHP has a negative impact on human and animal health, and thus toxicity caused by DEHP is increasingly serious health concern. Nevertheless, DEHP-induced liver damage in quail remains unclear. To investigate the mechanism of liver damage caused by DEHP, male quail were treated with DEHP (250, 500, and 750 mg/kg) by gavage. Notably, DEHP exposure results in increased blood lipids and the accumulation of triglycerides (TG), total cholesterol (TC), and non-esterified fatty acid (NEFA) in the liver. Histopathological analysis showed that steatosis and inflammatory cell infiltration were observed in the liver tissue of quails exposed to DEHP. The results of Oil Red O staining displayed that DEHP induced lipid storage in the liver. Moreover, DEHP induced lipid metabolism disorders by activating the LXR / SREBP-1c and PPARα / γ signaling pathway. DEHP exposure obviously caused the up-regulation of pro-inflammatory cytokines ( NF-κB , IL-6 , IL-8 , IL-1β , and TNF-a ). This study showed that DEHP could induce lipid metabolism disorders and inflammatory response via LXR / SREBP-1c / PPARα / γ and NF-κB signaling pathways.
研究领域:
毒理学
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环境健康
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分子生物学
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病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Environmental Technology & Innovation
·
2021
·
IF 5.263
Zhong Lin,Weijian Zhang,Xiaoping Zhu,Weijian Wu,Yijie Chen,Gaoyang Li,Lei Ren,Shuwen Luo,Yucheng Xie,Yongxiang Huang,Xinzi Wang,Zhen Zhen,Dayi Zhang
Di-2-ethylhexylphthalate (DEHP) is a common plasticizer and widely detected in sediments, water and biota. For its strong reproductive toxicity, teratogenicity and poisonousness, many approaches are developed to remediate DEHP-contaminated soils. This study aimed to evaluate the roles of biochar in accelerating DEHP degradation, assess the impacts of biochar pyrolysis temperature on DEHP removal performance, and explore the underlying mechanisms. Biochar had a satisfactory performance in DEHP adsorption and followed a Freundlich isotherm, exhibiting proportional adsorption capabilities to pyrolysis temperature. Biochar amendment significantly accelerated soil DEHP degradation, and the degradation efficiency ranged from 61.4% to 82.2% and increased with biochar pyrolysis temperature. Biochar remarkably changed soil physiochemical properties by increasing soil pH, organic matter and humus. Soil bacterial community was altered with biochar amendment that the relative abundance of Nocardioides , Marinobacter , Rhodococcus and Gramella increased. Our findings suggested that biochar-assisted bioremediation has a huge potential in soil DEHP degradation and pyrolysis temperature is a critical factor affecting the performance. Our work characterize biochar at different pyrolysis temperatures and explored the underlying mechanisms of biochar-assisted DEHP bioremediation, offering both scientific and practical hints for DEHP bioremediation in coastal sediments.
研究领域:
环境科学
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土壤学
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微生物学
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污染控制
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生物修复
✓ 已验证
产品关联
DOI
高影响因子
REPRODUCTIVE TOXICOLOGY
·
2021
·
IF 3.143
Jiadong Chen,Lian Kang,Junke Wang,Yuhao Wu,Lindong Han,Xiangqin Zheng,Yuexin Wei,Tianxin Zhao,Lianju Shen,Chunlan Long,Guanghui Wei,Shengde Wu
Di-(2-ethylhexyl) phthalate (DEHP) is an environmental endocrine disruptor that accumulates in organisms in various ways and induces male reproductive system disorders. In this study, we established a testicular injury model by gavage with different concentrations of DEHP. The testes were then collected for RNA sequencing (RNA-seq), and the results were analyzed by bioinformatics and verified by experiments. Our research results show that different concentrations of DEHP interfere with testicular development differently. Weighted gene coexpression network analysis (WGCNA) generated sixteen modules and identified the turquoise module as key. Then, estrogen receptor 1 (ESR1), filamin A (Flna) and Furin were identified as hub genes. qPCR and immunohistochemistry results revealed that all three hub genes were upregulated. We detected the locations of these genes by immunohistochemistry. ESR1 was mainly located in Leydig cells; Flna immunostaining is observed in the Leydig and some germ cells and Furin staining was seen in almost all types of testicular cells. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed enrichment mainly in MAPK signaling pathways, p53 signaling pathways, HIF-1 signaling pathways, protein processing in the endoplasmic reticulum, apoptosis, the cell cycle, RNA degradation, etc. This is the first study using WGCNA to investigate the mechanism of DEHP-induced injury in the prepubertal testis, providing new research angles to further understand the mechanism of DEHP-induced injury in the prepubertal testis.
研究领域:
毒理学
·
生殖生物学
·
分子生物学
·
生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2022
·
IF 10.753
Haowei Fu,Xiaofang Zhu,Qiannan Di,Jiahui Sun,Qianqian Jiang,Qian Xu
Di(2-ethyl-hexyl) phthalate (DEHP), an environmental endocrine disruptor, can destroy the sperm genomic integrity and impairs spermatogenesis. N6-methyladenosine (m6A) is involved in the cellular effects of DEHP. However, the genotoxic effect of DEHP on spermatocytes and the possible role of m6A in this process remain unclear. This study demonstrated that m6A alleviates DEHP genotoxicity in GC-2 cells. In DEHP-treated mice, DNA double-strand breaks (DSBs) were induced in the testis and spermatocytes. To further explore the molecular mechanism of DEHP genotoxicity on spermatocytes, GC-2 cells were exposed to DEHP. DEHP produced distinct genotoxicity and caused DSBs, which led to the inhibition of DNA synthesis and cell cycle arrest. The DNA damage response (DDR) was initiated to repair the DSBs induced by environmentally relevant levels of DEHP (100 μM and 200 μM). During this process, METTL3 upregulated m6A, which facilitated the DDR via stabilizing the DNA damage repair factors ( Rad51 and Xrcc5 ) mRNA to maintain the pro-survival state. Moreover, Mettl3 knockdown partially inhibited DDR. Interestingly, high-dose DEHP (400 μM and 600 μM) directly induced apoptosis rather than the pro-survival state. Altogether: METTL3-mediated m6A participates in maintaining the pro-survival state by upregulating DDR, providing guidance for mitigating the genotoxicity of environment-related level DEHP exposure.
研究领域:
毒理学
·
生殖生物学
·
分子生物学
·
环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2021
·
IF 6.291
Rui Tao,Hanjie Zhang,Xiuping Gu,Baowei Hu,Jun Li,Guixin Chu
Phthalic acid esters (PAEs) pollution has become an increasing issue worldwide, but little is known about its effects on ammonia-oxidizers and nitrous oxide (N 2 O) in the soil environment. Here, a 50-day soil microcosm experiment was conducted using low and high doses bis (2-Ethylhexyl) phthalate (DEHP) to estimate the effect of DEHP exposure on soil N 2 O emissions and the nitrifying community in calcareous soil. The results showed that DEHP exposure at 10 and 100 mg kg -1 doses significantly reduced N 2 O by 67.5% and 73.6%, respectively, relative to the DEHP absent treatment. The microbial biomass carbon and nitrogen (MBC and MBN) were consistently and significantly decreased with DEHP exposure at 5, 22, and 50 days after incubation, especially with high-dose. The bipartite association networks showed that DEHP exposure changed the compositions of both ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) communities. Moreover, the AOA and AOB amoA gene abundances were significantly decreased by DEHP addition to the soil ( P < 0.05). Random forest modeling showed that the AOB Shannon index and pH were the most important biotic and abiotic factors affecting N 2 O emissions in the soil with DEHP exposure, respectively. Partial least squares path modeling (PLS-PM) demonstrated that the reduction of N 2 O emissions due to DEHP exposure was mainly ascribed to the changes of the AOB community. The results from this study highlight the toxicity of DEHP on the ammonia oxidizers, and its mitigating effect on N 2 O emissions in the soil where ammonia-oxidation is largely driven by AOB.
研究领域:
环境科学
·
土壤微生物学
·
生态毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2018
·
IF 4.61
Hai-Ming Zhao,Rui-Wen Hu,Xue-Xue Chen,Xue-Bin Chen,Huixiong Lü,Yan-Wen Li,Hui Li,Ce-Hui Mo,Quan-Ying Cai,Ming-Hung Wong
A novel bacterial strain designated as Rhodococcus pyridinivorans XB, capable of utilizing various endocrine disruptor phthalates or phthalic acid (PA) as sole source of carbon and energy, was isolated from activated sludge. Under the optimal culture conditions (pH 7.08, 30.4 °C, inoculum size (OD 600 nm ) of 0.6) obtained by response surface methodology, di-(2-ethylhexyl) phthalate (DEHP, 200 mg/L) could be degraded by strain XB with a removal rate of 98% within 48 h. Under the observation of an atomic force microscope, it was confirmed that DEHP did not inhibit the growth of strain XB which might produce some extracellular polymeric substances as a response to DEHP stress, resulting in rapid degradation of DEHP. At initial concentrations of 50–800 mg/L DEHP, its degradation curves were well fitted with the first-order kinetic model, and the half-life of DEHP degradation varied from 5.44 to 23.5 h. The degradation intermediates of DEHP were identified by both GC–MS and high performance liquid chromatography–time of flight-mass spectrometry (HPLC–TOF-MS). Significant up-regulation was observed for the relative expression levels of genes (i.e., phthalate hydrolase, PA 3,4-dioxygenase, protocatechuate 3,4-α and 3,4-β dioxygenase) involved in DEHP degradation determined by real-time quantitative PCR (RT-qPCR). A DEHP biodegradation pathway by strain XB was proposed based on the identified intermediates and the degrading genes. Bioaugmentation of DEHP-contaminated soils with strain XB could efficiently promote DEHP removal, offering great potential in bioremediation of DEHP-contaminated environment.
研究领域:
环境微生物学
·
生物修复
·
分子生物学
·
环境工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）