ENVIRONMENTAL POLLUTION
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2023
·
IF 8.9
Yifan Hong,Xiazhu Zhou,Qi Li,Jing Chen,Yuexin Wei,Siyuan Wang,Xiangqin Zheng,Jie Zhao,Chengjun Yu,Jun Pei,Jie Zhang,Chunlan Long,Lianju Shen,Shengde Wu,Guanghui Wei
Di (2-ethylhexyl) phthalate (DEHP), one of phthalic acid esters, has been widely used in daily products. Its main metabolite, mono (2-ethylhexyl) phthalate (MEHP) was reported to possess higher testicular toxicity than DEHP. To explore the precise mechanism in MEHP-induced testis damage, multiple transcriptomic sequencing was employed in spermatogonia cell line GC-1 cells treated with MEHP (0, 100, and 200 μM) for 24 h. Integrative omics analysis and empirical validation revealed that Wnt signaling pathway was downregulated and wnt10a , one of hub genes, may be the key player in this process. Similar results were observed in DEHP-exposed rats. MEHP-induced disturbance of self-renewal and differentiation was dose-dependent. Moreover, self-renewal proteins were downregulated; the differentiation level was stimulated. Meanwhile, GC-1 proliferation was decreased. Stable transformation strain of wnt10a overexpression GC-1 cell line constructed from lentivirus was utilized in this study. The upregulation of Wnt10a significantly reversed the dysfunction of self-renewal and differentiation and promoted the cell proliferation. Finally, retinol, predicted to be useful in CONNECTIVITY MAP (cMAP), failed to rescue the damage caused by MEHP. Cumulatively, our findings revealed that the downregulation of Wnt10a induced the imbalance of self-renew and differentiation, and inhibition of cell proliferation in GC-1 cells after MEHP exposure.
研究领域:
毒理学
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分子生物学
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细胞生物学
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生殖生物学
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高影响因子
ENVIRONMENTAL POLLUTION
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2026
·
IF 7.2
Yanan Sun,Yuqing Fan,Yao Dang,Ping Ding,Xin Li,Gang Li,Haojie Luo,Jianliang Zhao,Guocheng Hu
Phthalates (PAEs) have attracted widespread attention as ubiquitous environmental contaminants. Among them, di-(2-ethylhexyl) phthalate (DEHP) is the most prevalent, particularly in the manufacturing of polyvinyl chloride. Although the direct toxic effects of DEHP on exposed individuals are well documented, far less is known about the potential for parentally transferred DEHP to induce adverse outcomes in unexposed offspring. In this study, adult zebrafish were chronically exposed to environmentally relevant concentrations of DEHP (0, 0.3, 3, and 30 μg/L) and subsequently spawned in DEHP-free water. DEHP accumulated in parental gonads and was transferred to unexposed F1 embryos. Compared to controls, offspring from parents exposed to 30 μg/L DEHP showed significantly increased embryo diameter and markedly impaired locomotor activity under light-dark cycles. Integrated multi-omics analysis further revealed that iba57 (mitochondrial function) and a2m3a (neurodevelopment) were consistently dysregulated at both mRNA and protein levels, linking the observed phenotypes to mitochondrial dysfunction and neurodevelopmental disruption. These findings demonstrate that even at environmentally relevant concentrations, parentally transferred DEHP can induce persistent effects in unexposed offspring, suggesting that current ecological risk assessment frameworks may underestimate the long-term risks of DEHP.
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International Journal of Environmental Research and Public Health
·
2017
·Vol. 14
·期 1
·44
·
IF 2.101
Xinwen Dong,Jin Dong,Yue Zhao,Jipeng Guo,Zhanju Wang,Mingqi Liu,Yunbo Zhang,Xiaolin Na
Di-(2-ethylhexyl)phthalate (DEHP) was a widely used chemical with human toxicity. Recent in vivo and in vitro studies suggested that DEHP-exposure may be associated with altered serum thyroid hormones (THs) levels, but the underlying molecular mechanisms were largely unknown. To explore the possible molecular mechanisms, 128 Wistar rats were dosed with DEHP by gavage at 0, 150, 300, and 600 mg/kg/day for 3 months (M) and 6 M, respectively. After exposure, expression of genes and proteins in the thyroid, pituitary, and hypothalamus tissues of rats were analyzed by Q-PCR and western blot, while the sera and urine samples were assayed by radioimmunoassay and ELISA. Results showed that serum THs levels were suppressed by DEHP on the whole. DEHP treatment influenced the levels of rats’ thyrotropin releasing hormone receptor (TRHr), Deiodinases 1 (D1), thyroid stimulating hormone beta (TSHβ), sodium iodide symporter (NIS), thyroid stimulating hormone receptor (TSHr), thyroperoxidase (TPO), thyroid transcription factor 1 (TTF-1), and thyroglobulin (TG) mRNA/protein expression in the hypothalamus-pituitary-thyroid (HPT) axis and decreased urine iodine. Taken together, observed findings indicate that DEHP could reduce thyroid hormones via disturbing the HPT axis, and the activated TSH/TSHR pathway is required to regulate thyroid function via altering TRHr, TSHβ, NIS, TSHr, TPO, TTF-1 and TG mRNA/protein expression of the HPT axis.Keywords:DEHP;hypothalamus-pituitary-thyroid axis;TSH/TSHR;signaling pathways;molecular mechanisms;thyroid function
研究领域:
毒理学
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内分泌学
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分子生物学
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高影响因子
WATER RESEARCH
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2022
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IF 13.4
Hongping Liao,Shulin Liu,Muhammad Junaid,Dandan Gao,Wenjie Ai,Guanglong Chen,Jun Wang
Organic pollutants such as di-(2-ethylhexyl) phthalate (DEHP) interact with nanoplastics (NPs) and change their bioavailability and toxicity to aquatic organisms. This study aims to assess the ecotoxicological impacts of NPs in the presence and absence of DEHP on juvenile largemouth bass (LMB) Micropterus salmoides . Therefore, LMB was fed with diets containing various concentrations (0, 2, 10, and 40 mg/g) of polystyrene nanoplastics (PSNPs) by the weight of diets. After a 21-day of PSNPs dietary exposure, LMB was treated with DEHP at 450 μg/L through waterborne exposure for three days. Our results showed that PSNPs were accumulated in the intestinal tissues, which significantly decreased the feeding and growth rates in LMB. The histopathological analysis showed the intestine and liver of LMB were subjected to various degrees of structural damage caused by PSNPs, and DEHP-PSNP co-exposure enhanced those histopathological damages in both tissues. Additionally, the co-exposure induced oxidative stress in terms of increased activities of glutathione S-transferase, catalase, and superoxide dismutase enzymes in the liver, intestine, spleen, and serum. Furthermore, the co-exposure significantly changed the intestinal microbial composition, i.e., the decrease in the abundance of probiotics (Bacteroidetes and Proteobacteria) and the increase in pathogenic bacteria (Firmicutes) posed a great threat to fish metabolism and health. Therefore, this study highlights that the presence of DEHP enhances the toxicity of NPs on LMB in freshwater and suggests the regulated use of plastic and its additives for improving the health status of aquaculture fish for food safety in humans.
研究领域:
环境科学
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生态毒理学
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水产养殖
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高影响因子
JOURNAL OF POLYMERS AND THE ENVIRONMENT
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2020
·Vol. 28
·期 8
·2101-2107
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IF 2.572
Ma Yufeng,Song Fei,Kong Qinying,Li Qiaoguang,Jia Puyou,Zhou Yonghong
Dioctyl phthalate (DEHP), as the most used commercial plasticizer, has been restricted in many polymer products due to its reproductive toxicity to human body. In this study, castor oil based polyol ester(CPE) was synthesized via a simple and efficient way and used as a sustainable plasticizer in poly(vinyl chloride) (PVC) films to replace toxic DEHP. The chemical structure of the obtained bio-based plasticizer was characterized. The oral toxicity test indicated that CPE had toxic doses of over 3000 mg/kg. Tg of PVC films decreased from 87.4 to 19.1 °C, which is lower than PVC-DEHP systems. The tensile strength and elongation at break of PVC films plasticized with 50 phr CPE is 12.10 MPa and 450.15% respectively, which shows more flexible than PVC/50 prh DEHP samples.The DMA and tensile tests results indicated that the plasctizing effect of CPE was more excellent than DEHP. DEHP can be completely replaced with CPE in flexible PVC products.
研究领域:
材料科学
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化学工程
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环境科学
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CHEMICO-BIOLOGICAL INTERACTIONS
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2026
·
IF 5.2
Dui Sun,Qi Yang,Zhi-Hui Gong,Meng-Lei Feng,Zhi-Wen Jia,Bin-Shuo Yang,Zhao-Yu Jiang,Chun-Ru Song,Fang-Rui Xue,Xiao-Jie Zhang,Hao-Yang Zhang,Chun-Lan Zhang,Xiao-Yi Zhang,Cheng-Guang Liang
Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental endocrine-disrupting chemical known to impair female reproductive function. However, effective mitigation strategies and their underlying molecular mechanisms remain incompletely understood. Quercetin (QUE), a natural flavonoid with potent antioxidant and anti-apoptotic properties, represents a promising therapeutic candidate. In this study, we established a mouse model to evaluate the protective efficacy of QUE against DEHP-induced oocyte toxicity. Female ICR mice were treated with DEHP (500 mg/kg/day) with or without QUE (100 mg/kg/day) for 45 days. QUE co-treatment significantly alleviated DEHP-induced estrous cycle disruption, restored the ovarian reserve, and enhanced both nuclear and cytoplasmic oocyte maturation. Mechanistically, integrated network pharmacology and molecular docking analyses identified NRF2 and SIRT1 as key targets of QUE. Western blot validation confirmed that QUE reversed the DEHP-induced downregulation of NRF2 and normalized the compensatory overexpression of SIRT1. Functionally, QUE mitigated DEHP-triggered mitochondrial dysfunction, including aberrant clustering and loss of membrane potential, and suppressed the Bax/Caspase-dependent apoptotic pathway by downregulating Bax , Caspase-3 , and Caspase-9 while upregulating Bcl-2 . These protective effects ultimately led to improved preimplantation embryo development, reduced blastocyst apoptosis, normalized litter size, and prevention of abnormal postnatal catch-up growth trajectories in offspring. Collectively, our findings demonstrate that QUE counteracts DEHP-induced reproductive toxicity by preserving mitochondrial integrity and inhibiting apoptotic signaling via modulation of the SIRT1/NRF2 axis, providing a strong mechanistic foundation for dietary interventions against phthalate-associated female subfertility.
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REPRODUCTIVE TOXICOLOGY
·
2025
·
IF 2.8
Li-Ping Tan,Liu Yuan,Yan Zhang,Jun-Lin He,Xin Yin,Yi-Dan Ma,Xue-Mei Chen,Wei-Ke Li,Fang-Fang Li,Ru-Fei Gao
DEHP is a pervasive endocrine disrupting chemical with multiple adverse effects on the female reproductive system. However, its impact on endometrial decidualization, the foundation for embryo implantation and successful pregnancy, remains poorly defined, and the underlying regulatory mechanisms have been rarely explored. In present study, we utilized several assays with DEHP-exposed mouse decidual tissues to clarify whether DEHP exposure confers adverse effects on decidualization. The results showed that 1000 mg/kg/d DEHP exposure led to a significant reduction in the weight and area of the uterine deciduoma, accompanied by a significant decrease in the expression of decidualization markers on GD6, GD8 of pregnancy, and PD8 of pseudopregnancy in mice. Moreover, the in vitro findings revealed that exposure to 12.5 μM MEHP, the primary and active metabolite of DEHP, disturbed the cytoskeletal remodeling and downregulated the marker molecules during endometrial stromal cell decidualization. Meanwhile, we detected that Mtmr6 as identified by proteomics analysis, was up-regulated after DEHP and MEHP exposure in vivo and in vitro . Knockdown of Mtmr6 alleviated the deficiencies in stromal cell decidualization induced by DEHP’ metabolite MEHP. Furthermore, we also found that the active-site residue ALA-131 of Mtmr6 may be the direct binding site for MEHP by performing molecular docking. This study uncovered the adverse effects of DEHP on endometrial decidualization and revealed the possible mechanisms, providing potential strategies for minimizing their toxicological effects on female reproductive health.
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2025
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IF 4.6
Anjie Guo,Yu Wu,Yunkai Xie,Wang Guo,Yiqing Guo,Xinai Zhang,Wen Zhang,Xiaobo Zou,Zongbao Sun
Di-(2-ethylhexyl) phthalate (DEHP) can leach into food and the environment, posing health and ecological risks. This paper introduces a novel CRISPR-based fluorescent aptasensor for on-site DEHP detection. The aptasensor selectively binds to DEHP, triggering a competitive displacement reaction that releases an Aptamer-dsDNA probe. After magnetic separation, the supernatant is analyzed via a Cas12a reporter system, where Cas12a activation cleaves a FAM-BHQ reporter, generating fluorescence. Combined with smartphone imaging, this method enables rapid result acquisition. The aptasensor shows high selectivity and sensitivity, detecting DEHP from 1 pg/mL to 1 μg/mL, with a lower limit of 0.15 pg/mL. It effectively detects DEHP in various real samples, offering reliable visual monitoring. This method offers a rapid and effective on-site detection strategy for food safety and environmental pollution monitoring.
研究领域:
食品安全
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环境监测
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生物传感器
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分子诊断
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CRISPR技术
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2026
·
IF 6.6
Songyi Ye,Shuang Wu,Gutong Yuan,Jie Xu,Bocheng Cai,Jinling Chen,Wenliang Ge
About 1%-9% of full-term male newborns suffer from cryptorchidism, which is one of the most common congenital abnormalities in the male reproductive tract. Dysregulation of the crosstalk between macrophages and Leydig cells has been implicated in its pathogenesis. However, the mechanisms by which environmental endocrine disruptors disrupt the crosstalk between macrophages and Leydig cells remain insufficiently defined. In this study, it was demonstrated that prenatal exposure to DEHP induces cryptorchidism and defective spermatogenesis in C57BL/6 male offspring, accompanied by marked reductions in Leydig cell quantity, testosterone production and steroidogenic enzyme expression. Notably, Trem2, an immunoregulatory receptor expressed on testicular macrophages, was significantly downregulated following DEHP exposure. Further investigation revealed that MEHP-activated macrophages exacerbate the inhibitory effects of MEHP on Leydig cell proliferation and steroidogenic function. Transcriptomic profiling of macrophages with Trem2 overexpression identified Mical1 as the most significantly upregulated gene. In vitro , MEHP stimulation led to decreased expression of Trem2, Mical1, and Erk in macrophages. Trem2 overexpression restored Mical1 and Erk signaling and Trem2 activation rescued Leydig cell proliferative capacity, while Trem2 silencing further suppressed Mical1 and Erk expression and exacerbated Leydig cell dysfunction. Moreover, Mical1 overexpression reversed the MEHP-induced downregulation of Mical1 and Erk. These findings highlight the Trem2-Mical1-Erk axis as a critical immunoregulatory pathway linking DEHP-induced macrophage activation to testosterone insufficiency. The discovery provides new insights into the etiology of cryptorchidism and identifies potential targets for DEHP-induced cryptorchidism.
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JOURNAL OF HAZARDOUS MATERIALS
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2025
·
IF 11.3
Ruomeng Shi,Xianxu Li,Huijuan Lv,Qian Wang,Xiangfeng Yao,Yeji Zhang,Huiyan Yang,Jia Ding,Lubsan-zondy Budazhapov,Jun Wang
s Phthalate esters (PAEs) are typically released from agricultural plastic films and veterinary antibiotics introduced through livestock manure. They often accumulate in agricultural soils, posing complex ecological risks and severe biological effects that are not yet fully understood. Therefore, this study investigated the ecotoxicity and risks of di(2-ethylhexyl) phthalate (DEHP), sulfadiazine (SDZ), and their co-exposure on earthworms. DEHP, SDZ, and their co-exposure was found to significantly impair earthworm growth and reproduction, induced oxidative stress, and altered the expression of functional genes ( tctp , ann , sod , cat , hsp70 , er ). Both DEHP and SDZ strongly bound to key earthworm proteins (SOD and TCTP), further supporting the evidence of oxidative stress and adverse effects on growth and development. Risk assessment revealed that DEHP exacerbated the reproductive and oxidative stress compared to SDZ and the co-exposure. Furthermore, histopathological and flow cytometric results suggested antagonistic interactions between DEHP and SDZ during co-exposure. Transcriptomics data demonstrated that SDZ activated pathways related to oxidative stress repair (peroxisome pathways) and detoxification (glutathione metabolism) in earthworms, which explains the relatively lower toxicity of co-exposure. Overall, these findings provide multi-level insights into the antagonistic effects of compound pollution in soil ecosystems and support the ecological risk assessment of PAEs and antibiotics.
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JOURNAL OF ENVIRONMENTAL MANAGEMENT
·
2026
·
IF 9.2
Jingwen Zhang,Xiaowen Liu,Zhongkun Du,Bing Li,Jun Wang,Jinhua Wang,Lusheng Zhu
The widespread application and residual accumulation of polyethylene (PE) agricultural films in saline soils have contributed to the co-occurrence of PE particles and plasticizers such as di-(2-ethylhexyl) phthalate (DEHP). Although the environmental presence of these agricultural film components is recognized, their combined ecological risks and the subsequent management challenges they pose remain poorly understood. The present study evaluated the comprehensive toxicity effects and ecotoxicological risk implications of DEHP alone and in co-exposure with PE on earthworms within a salinized soil environment using a multi-biomarker evaluation approach. The results revealed that both treatments induced oxidative stress, DNA damage, tissue damage, and molecular responses potentially linked to growth and reproduction. Notably, DEHP + PE co-exposure induced stronger comprehensive toxicity effects than DEHP alone in a concentration-dependent manner under the tested salinized soil conditions. To elucidate the underlying pathways and identify potential early-warning indicators for soil monitoring, transcriptomics and molecular docking were employed. Transcriptomic profiling indicated that solitary DEHP exposure primarily disrupted digestive metabolism and cellular processes. In contrast, co-exposure to DEHP and PE significantly impaired neural and vascular development pathways. Molecular docking analysis further supported these findings by illustrating the specific binding interactions of DEHP with key target proteins. Ultimately, the current study integrates multi-level biological evidence to support ecotoxicological risk evaluation of DEHP and DEHP + PE co-exposure, offering potential implications for future ecological risk assessment, soil monitoring, and sustainable management of agricultural plastic residues in saline ecosystems.
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ENVIRONMENTAL SCIENCE & TECHNOLOGY
·
2026
·
IF 12.2
Qiang Li,Kaisheng Hong,Chenke Xu,Linwan Li,Geng Yue,Cheng Xu,Min Yang,Jianying Hu
Abstract While exposure to PPAR active compounds can lead to various adverse health effects, studies on the environmental contaminants and their transformation products with PPAR activity remain limited. This study employed PPARγ protein affinity selection-mass spectrometry (AS-MS) to comprehensively identify and prioritize PPARγ-active contaminants in the Yangtze and Yellow Rivers, key drinking water sources in China. From wastewater treatment plant effluents, river, and source water samples, 61 PPARγ ligands were identified, including 18 antagonists not reported previously. Notably, a novel biodegradation product of di-2-ethylhexyl phthalate (DEHP), phthalic acid 1-(2-ethylhexyl) 2-(2-ethyl-5-carboxypentyl) ester (5CX-DEHP), was discovered and characterized as a potent PPARγ antagonist (IC50 = 8.5 μM). Semi-quantification revealed total concentrations of 61 chemicals ranging from 965.2 to 5748 ng/L in source waters, with priority agonistic chemicals such as 4-dodecylbenzenesulfonic acid and priority antagonistic chemicals such as 2-amino-6-methylmercaptopurine and 5CX-DEHP posing high ranking. This study comprehensively revealed the widespread occurrence of PPARγ agonistic and antagonistic chemicals in the water samples and identified a previously overlooked transformation product of DEHP as a relatively strong PPARγ antagonist.
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危险品化学品经营许可证（带存储）