New insights into the mechanism of phthalate-induced developmental effects

Mu, Xiyan; Huang, Ying; Li, Jia; Yang, Ke; Yang, Wenbo; Shen, Guoan; Li, Xuxing; Lei, Yunlei; Pang, Sen; Wang, Chengju; Li, Xuefeng; Li, Yingren

doi:10.1016/j.envpol.2018.05.095

Cited by 58 publications

(34 citation statements)

References 68 publications

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“…Exposures from 3 to 24 hpf to 5.2 nM DEHP significantly reduced the body length, tail length as well as yolk extension length of zebrafish embryos compared to the control, while no effects were observed with DEHP exposures at 3–48 hpf and 3–72 hpf [ 45 ]. Opposite results were obtained by Ustundag et al and Mu et al in that DEHP could cause yolk sac edema with longer treatment durations [ 44 , 48 ]. Mu et al found that 250 µg/L of DEHP significantly induced yolk sac edema in 48 hpf embryos as well as increased ratios of yolk sac area to fish body area in DEHP-dosed embryos when compared with control embryos [ 48 ].…”

Section: Acute Effects Induced By Acute Exposurementioning

confidence: 85%

“…Opposite results were obtained by Ustundag et al and Mu et al in that DEHP could cause yolk sac edema with longer treatment durations [ 44 , 48 ]. Mu et al found that 250 µg/L of DEHP significantly induced yolk sac edema in 48 hpf embryos as well as increased ratios of yolk sac area to fish body area in DEHP-dosed embryos when compared with control embryos [ 48 ]. In a separate study, Mu et al reported that exposure to as low as 2.5 µg/L of DEHP could cause yolk sac edema in 72 hpf embryos [ 44 ].…”

Section: Acute Effects Induced By Acute Exposurementioning

confidence: 85%

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Review on Toxic Effects of Di(2-ethylhexyl) Phthalate on Zebrafish Embryos

Kwan

Roy

2021

Toxics

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Di(2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer in consumer products. People are continuously exposed to DEHP through ingestion, inhalation and dermal absorption. From epidemiological studies, DEHP has been shown to associate with various adverse health effects, such as reproductive abnormalities and metabolic diseases. Health concerns have been raised regarding DEHP exposures; therefore, relevant risk assessment has become necessary through toxicological testing of DEHP. In the past 10 years, an increasing number of DEHP toxicity studies have been using zebrafish embryos as an in vivo model due to their high fecundity, rapid embryonic development as well as optical transparency, which have now been established as an alternative of the more conventional rodent model. The aim of the present paper is to review the effects of acute (from embryo stage to ≤1 week) and chronic (from embryo stage to >1 week) DEHP exposures on zebrafish, which start from the embryonic stage, and to analyze acute and potential long-term effects induced by acute exposure and effects induced by chronic exposure of DEHP upon subjecting to exposures, starting from the embryonic stage to different developmental stages, with a view to facilitate risk assessments on DEHP exposures.

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Section: Acute Effects Induced By Acute Exposurementioning

confidence: 85%

Section: Acute Effects Induced By Acute Exposurementioning

confidence: 85%

Review on Toxic Effects of Di(2-ethylhexyl) Phthalate on Zebrafish Embryos

Kwan

Roy

2021

Toxics

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“…The copyright holder for this preprint this version posted July 22, 2021. ; https://doi.org/10.1101/2021.07.19.21260700 doi: medRxiv preprint Complementary enrichment analysis using proteomic data revealed biological processes associated with DBP (xenobiotic stimulus, lipoprotein metabolism, lipid catabolism, and regulation of FA and TG catabolism) and DEHP (lipase activity regulation, lipid absorption, lipid catabolism and metabolism) [42]. As noted in the introduction, one suggested mechanism is that phthalates, known as PPAR-agonists, are interfering with peroxisome-proliferator active receptor gamma (PPARγ) and therefore disrupting lipid metabolism [21,22].…”

Section: Discussionmentioning

confidence: 99%

Maternal Urinary Phthalate Metabolites are Associated with Lipidomic Signatures Among Pregnant Women in Puerto Rico

Ashrap

Aung

Watkins

et al. 2021

Preprint

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Background: Phthalates have been reported to alter circulating lipid concentrations in animals, and investigation of these associations in humans will provide greater understanding of potential mechanisms for health outcomes. Objective: to explore associations between phthalate metabolite biomarkers and lipidomic profiles among pregnant women (n = 99) in the Puerto Rico PROTECT cohort. Methods: We measured 19 urinary phthalate metabolites during 24-28 weeks of pregnancy. Lipidomic profiles were identified from plasma samples by liquid chromatography-mass spectrometry-based shotgun lipidomics. Relationships between phthalates and lipid profiles were estimated using compound-by-compound comparisons in multiple linear regression and dimension reduction techniques. We derived sums for each lipid class and sub-class (saturated, monounsaturated, polyunsaturated) which were then regressed on phthalates. Associations were adjusted for false discovery. Results: After controlling for multiple comparisons, 33 phthalate-lipid associations were identified (q-value<0.05), and diacylglycerol 40:7 and plasmenyl-phosphatidylcholine 35:1 were the most strongly associated with multiple phthalate metabolites. Metabolites of di-2-ethylhexyl phthalate, bis(2-ethylhexyl) phthalate, dibutyl phthalates, and diisobutyl phthalate were associated with increased ceramides, lysophosphatidylcholines, lysophosphatidylethanolamines, and triacylglycerols, particularly those containing saturated and monounsaturated fatty acid chains. Significance: Characterization of associations between lipidomic markers and phthalates during pregnancy will yield mechanistic insight for maternal and child health outcomes.

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“…The elevated levels of DEHP have been reported in freshwater resources, which provides water supply for drinking and domestic utilities, and this could ultimately pose a threat to environmental and human health [38]. In the previous studies, the toxicity of DEHP and its derivative MEHP had mainly focused on the developmental and reproduction effects or organogenesis through various biological pathways in fish [39][40][41]. However, the eco-toxicological risks of DEHP with environmental concentrations on freshwater fish health including the development and intestinal homeostasis, especially their underlying relationships with the disruption of intestinal bacterial functions were still unclear.…”

Section: Discussionmentioning

confidence: 99%

DEHP chronic exposure disturbs the gut microbial community and metabolic homeostasis: Gender-based differences in zebrafish

Pei

Jia

Xin

et al. 2020

Preprint

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Background: Di-(2-ethylhexyl) phthalate (DEHP), a predominant phthalate ester (PAE), exhibits various toxic potentials with environmental and human health risks. However, the chronic effects of DEHP exposure on gut microbiota and associated host’s health are still largely unexplored. Here, zebrafish were exposed to relative environmental levels (0-100 μg/L) of DEHP from embryos to adult (3.5 months), then the developmental indexes and microbiota as well as the related energy metabolites in gut tissues were checked to unveil the effects during the growth progress. Results: The results indicated that the composition of gut microbiota was different among male and female adult zebrafish, and DEHP disrupted the diversity and richness of the bacterial community. The histopathological analysis of intestinal tissues revealed the decrease of villus length and tunica muscularis thickness, especially the goblet cells per villi in male fish. Moreover, energy metabolites in gut tissues were actively increased at lower levels groups, which probably contribute to the condition factor of host. For immune-related genes, the expression levels of il-8 was increased both in female and male fish in the lowest concentration (10 μg/L), but the tlr-5 and il-1β genes were in the different response with significantly decreased in female fish. Conclusion: Taken all together, those results indicated that chronic exposure to DEHP led to zebrafish obesity with the disturbed bacterial community in the gut and related metabolism pathways. Those findings provided deep insights on the perturbation of gut microbiota, metabolic homeostasis, and gender-based differences by DEHP exposure.

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New insights into the mechanism of phthalate-induced developmental effects

Cited by 58 publications

References 68 publications

Review on Toxic Effects of Di(2-ethylhexyl) Phthalate on Zebrafish Embryos

Review on Toxic Effects of Di(2-ethylhexyl) Phthalate on Zebrafish Embryos

Maternal Urinary Phthalate Metabolites are Associated with Lipidomic Signatures Among Pregnant Women in Puerto Rico

DEHP chronic exposure disturbs the gut microbial community and metabolic homeostasis: Gender-based differences in zebrafish

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