Exposure to Di-(2-ethylhexyl) Phthalate During Perinatal Period Gender-Specifically Impairs the Dendritic Growth of Pyramidal Neurons in Rat Offspring

You, Mingdan; Dong, Jing; Fu, Yuanyuan; Cong, Zhangzhao; Fu, Hui; Wei, Lingling; Wang, Yi; Wang, Yuan; Chen, Jie

doi:10.3389/fnins.2018.00444

Cited by 29 publications

(25 citation statements)

References 83 publications

(98 reference statements)

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“…People are inevitably exposed to phthalate through environmental contamination. Exposure to DEHP was associated with a variety of toxicological outcomes in mammals, reproductive toxicity, 39 neurotoxicity, 40 carcinogenicity, 41 hepatotoxicity, 42 and lipid metabolism disruption. 43 In this study, we focused on the harmful effect of this plasticizer on HEK-293 cell line, given that the kidney is one of DEHP target organ.…”

Section: Discussionmentioning

confidence: 99%

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Di (2‐ethylhexyl) phthalate induces cytotoxicity in HEK‐293 cell line, implication of the Nrf‐2/HO‐1 antioxidant pathway

Amara

Timoumi

Graiet

et al. 2019

Environmental Toxicology

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The di (2‐ethylhexyl) phthalate (DEHP) is a plasticizer used in the polyvinyl chloride industry. Human exposure to this plasticizer is inevitable and contributes to several side effects. In this study, we examined whether DEHP induces apoptosis and oxidative stress in embryonic kidney cells (HEK‐293) and whether the nuclear factor E2‐related factor 2 (Nrf‐2)/heme oxygenase‐1 (HO‐1) antioxidant pathway is involved in the pathogenesis of this process. We demonstrated that DEHP is cytotoxic to HEK‐293 cells. It causes oxidative damage through the generation of free radicals, induces lipid peroxidation, and alters superoxide dismutase and catalase activities. Simultaneously, DEHP treatment decreases the expression and the protein level of Nrf‐2 and HO‐1. Inhibition of the Nrf‐2/HO‐1 pathway is related to the mitochondrial pathway of apoptosis. This apoptotic process is characterized by a loss of mitochondrial transmembrane potential (ΔΨm) and upregulation of the expression of caspase‐3 mRNA as well as its protein level.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Di (2‐ethylhexyl) phthalate induces cytotoxicity in HEK‐293 cell line, implication of the Nrf‐2/HO‐1 antioxidant pathway

Amara

Timoumi

Graiet

et al. 2019

Environmental Toxicology

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“…A common approach to assess the effects of perinatal exposure to phthalates is the maternal exposure model. In that sense, You et al (2018) investigated the effects of maternal DEHP exposure on dendritic development of hippocampal pyramidal neurons in a rat model. Wistar pregnant rats were intragastrically administered with DEHP from gestation day (GD) 0 to postnatal day (PND) 21; then, the offspring were sacrificed at PND 7, 14, and 21 to evaluate their dendritic length and complexity of dendritic arbors' pattern in pyramidal neurons of the hippocampus, as well as the expression of dendritic development‐related proteins (You et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

The detrimental effect of microplastics on critical periods of development in the neuroendocrine system

Solleiro‐Villavicencio

León

Río-Araiza

et al. 2020

Birth Defects Research

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As a result of human socioeconomic activity, industrial wastes have increased alarmingly. Plastic pollution is globally distributed across the world due to its properties of buoyancy and durability. Two broad classes of plastic-related chemicals are of critical concern for human health-bisphenol-A or BPA, and additives used in the synthesis of plastics, which are known as phthalates. Our exposure to them is ubiquitous because they are used in the production of materials that we use daily such as polycarbonate plastics, epoxy resins, flooring, automotive parts, medical devices, dental sealants, and children's toys. Since these compounds are not covalently bound to the products, they easily leach from them, leading to high human exposure. Both, BPA and phthalates, are endocrine-disruptor compounds (EDCs) with steroidogenic activity, and can bind to different receptors, such as estrogen, androgen, PPAR-γ, and AhR. These pathways are part of the complex regulatory neuroendocrine network, since its cellular components not only express neuroendocrine receptors, but synthesize and respond to several hormones and other endocrine ligands. On the other hand, the effects of BPA and phthalates on neuroendocrine diseases have been poorly studied and the available data are inconclusive. This can be attributed to the enormous variety of animal models and the different doses used in experiments or levels found in humans. However, what is clear is that exposure to both EDCs during critical life stages induces many changes in the neuroendocrine system of exposed humans that are correlated with different reproductive and neurological diseases.

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“…It has been thought that women, especially pregnant women, are more susceptible to DEHP than men in the same living environment [12]. Moreover, it was deemed that DEHP and MEHP could pass through the placental barrier and the imperfect fetal cerebral blood barrier to affect fetal development [131415]. Studies have shown that maternal exposure to DEHP exerted deleterious effects on fetal immune, cardiovascular and endocrine system development [16171819].…”

Section: Introductionmentioning

confidence: 99%

“…Although numerous studies on DEHP neurotoxicity have been conducted [1540414243444546], relatively little research has been done on its effect on the cerebellum, notably, toxicities and related mechanisms are still unclear. Therefore, the aim of the present study was to investigate the effects of DEHP on apoptosis in cerebellar granule cells (CGCs) and the underlying mechanisms involved.…”

Section: Introductionmentioning

confidence: 99%

Developmental Exposure to Di-(2-ethylhexyl) Phthalate Induces Cerebellar Granule Cell Apoptosis via the PI3K/AKT Signaling Pathway

Dong

Wang

et al. 2018

Exp Neurobiol

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Di-(2-ethylhexyl) phthalate (DEHP) is an ubiquitous environmental contaminant because of its extensive use in plastics and its persistence. As an environmental endocrine disruptor, it is suspected to interfere with neurodevelopment in people. However, evidence of the effects of maternal DEHP exposure on cerebellar development in offspring is scarce. The objective of this study was to investigate maternal exposure to DEHP and its effect on apoptosis of cerebellar granule cells (CGCs) and related mechanisms. Pregnant Wistar rats were administrated DEHP (0, 30, 300 and 750 mg/kg/d) by gavage from gestational day (GD) 0 to postnatal day (PN) 21. Primary CGCs were also exposed to mono-(2-ethylhexyl) phthalate (MEHP), the main metabolite of DEHP, for 24 h with concentrations of 0, 25, 100 and 250 µM. The CGCs of male offspring from 300 and 750 mg/kg/d DEHP exposure groups showed significantly increased apoptosis. In addition, the PI3K/AKT signaling pathway was inhibited in the male offspring of the 300 and 750 mg/kg/d DEHP exposure groups. However, effects on female pups were not obvious. Apoptosis was also elevated and the PI3K/AKT signaling pathway was inhibited after primary CGCs were exposed to MEHP. Furthermore, apoptosis was reduced after treatment with the PI3K/AKT signaling pathway activator, insulin-like growth factor (IGF) 1, and increased after treatment with LY294002, an inhibitor of the PI3K/AKT signaling pathway. These results suggested that maternal DEHP exposure induced apoptosis in the CGCs of male pups via the PI3K/AKT signaling pathway, and the apoptosis could be rescued by IGF1 and aggravated by LY294002.

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Exposure to Di-(2-ethylhexyl) Phthalate During Perinatal Period Gender-Specifically Impairs the Dendritic Growth of Pyramidal Neurons in Rat Offspring

Cited by 29 publications

References 83 publications

Di (2‐ethylhexyl) phthalate induces cytotoxicity in HEK‐293 cell line, implication of the Nrf‐2/HO‐1 antioxidant pathway

Di (2‐ethylhexyl) phthalate induces cytotoxicity in HEK‐293 cell line, implication of the Nrf‐2/HO‐1 antioxidant pathway

The detrimental effect of microplastics on critical periods of development in the neuroendocrine system

Developmental Exposure to Di-(2-ethylhexyl) Phthalate Induces Cerebellar Granule Cell Apoptosis via the PI3K/AKT Signaling Pathway

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