Acute postnatal exposure to di(2-ethylhexyl) phthalate adversely impacts hippocampal development in the male rat

Smith, Catherine A.; MacDonald, Amy M.; Holahan, Matthew R.

doi:10.1016/j.neuroscience.2011.06.082

Cited by 73 publications

(77 citation statements)

References 24 publications

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“…All of the dams were allowed to feed their offspring until weaning. The doses of DEHP in the present study were below the no observed adverse effect level (NOAEL, 48 mg kg À1 d À1 ) of DEHP (10, 50, and 200 mg kg À1 d À1 , converted to human equivalent dose based on the body surface area was approximately 0.81, 4.05, 16.2 mg kg À1 d À1 ) (Huang et al, 2004) and were previously found no reproductive toxicology (Smith et al, 2011).…”

Section: Animals and Treatmentmentioning

confidence: 39%

“…The worldwide consumption of phthalates exceeds five million metric tons annually (Singh and Li, 2012). Di-(2-ethylhexyl) phthalate (DEHP) is one of the most commonly phthalates, with majorly being used in plastics and many other products including food storage containers, toys, pharmaceuticals, cosmetics, and personal care products (Smith et al, 2011). Given the widespread use of these products, it is unavoidable for wildlife and human being exposed to DEHP.…”

Section: Introductionmentioning

confidence: 99%

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Perinatal exposure to di-(2-ethylhexyl) phthalate affects anxiety- and depression-like behaviors in mice

et al. 2015

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Section: Animals and Treatmentmentioning

confidence: 39%

Section: Introductionmentioning

confidence: 99%

Perinatal exposure to di-(2-ethylhexyl) phthalate affects anxiety- and depression-like behaviors in mice

et al. 2015

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“…Recent research has indicated that postnatal or prenatal exposure to DEHP impairs neurodevelopment (Smith et al 2011;Lim et al 2009;Carbone et al 2013;Wang et al 2014) and may lead to deregulation of neurofunction, hyperactivity, anxiety-like behavior and social impairment in experimental rodents or children (Masuo et al 2004;Engel et al 2009;Miodovnik et al 2011;Lien et al 2015). In this study, we observed the maternal DEHP exposure increased neurite length and number at the cortex of offspring, which agreed with Chen et al (2011), who found that treatment with MEHP, the DEHP metabolite, disturbed neural differentiation of PC12 cells toward an acetylcholine phenotype at the expense of dopamine phenotype, accompanied by promoted neurite outgrowth.…”

Section: Discussionmentioning

confidence: 99%

Maternal exposure to di-(2-ethylhexyl) phthalate exposure deregulates blood pressure, adiposity, cholesterol metabolism and social interaction in mouse offspring

et al. 2015

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Long-term exposure to di-(2-ethylhexyl) phthalate (DEHP) is highly associated with carcinogenicity, fetotoxicity, psychological disorders and metabolic diseases, but the detrimental effects and mechanisms are not fully understood. We investigated the effect of exposing mouse mothers to DEHP, and the underlying mechanism, on blood pressure, obesity and cholesterol metabolism as well as psychological and learning behaviors in offspring. Tail-cuff plethysmography was used for blood pressure measurement; Western blot used was for phosphorylation and expression of protein; hematoxylin and eosin staining, Nissl staining and Golgi staining were used for histological examination. The serum levels of cholesterol, triglycerides and glucose were measured by blood biochemical analysis. Hepatic cholesterol and triglyceride levels were assessed by colorimetric assay kits. Offspring behaviors were evaluated by open-field activity, elevated plus maze, social preference test and Morris water maze. Maternal DEHP exposure deregulated the phosphorylation of endothelial nitric oxide synthase and upregulated angiotensin type 1 receptor in offspring, which led to increased blood pressure. It led to obesity in offspring by increasing the size of adipocytes in white adipose tissue and number of adipocytes in brown adipose tissue. It increased the serum level of cholesterol in offspring by decreasing the hepatic capacity for cholesterol clearance. The impaired social interaction ability induced by maternal DEHP exposure might be due to abnormal neuronal development. Collectively, our findings provide new evidence that maternal exposure to DEHP has a lasting effect on the physiological functions of the vascular system, adipose tissue and nerve system in offspring.

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“…In fish, butyl benzyl phthalate (BBP, 0.1 mg/L) in water altered shoaling (a social behavior) and feeding behavior in three-spined sticklebacks (Wibe et al, 2002; Wibe et al, 2004). In rats, DEHP during perinatal development caused cognitive deficits in spatial memory (Li et al, 2013), which may be linked to a reduced hippocampal cell density in males (Smith et al, 2011). Single intracisternal injecions of dicyclohexyl phthalate ranging from 0.029 to 2.9 mg/ml (0.087-8.7 mM) five days after birth dose-dependently increased locomotor activity in adult male rats and decreased midbrain DA synthesis, transport and receptor signaling (Ishido et al, 2004).…”

Section: Bisphenol a And Phthalatesmentioning

confidence: 99%

Current concepts in neuroendocrine disruption

León-Olea

Martyniuk

Orlando

et al. 2014

General and Comparative Endocrinology

127

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In the last few years, it has become clear that a wide variety of environmental contaminants have specific effects on neuroendocrine systems in fish, amphibians, birds and mammals. While it is beyond the scope of this review to provide a comprehensive examination of all of these neuroendocrine disruptors, we will focus on select representative examples. Organochlorine pesticides bioaccumulate in neuroendocrine areas of the brain that directly regulate GnRH neurons, thereby altering the expression of genes downstream of GnRH signaling. Organochlorine pesticides can also agonize or antagonize hormone receptors, adversely affecting crosstalk between neurotransmitter systems. The impacts of polychlorinated biphenyls are varied and in many cases subtle. This is particularly true for neuroedocrine and behavioral effects of exposure. These effects impact sexual differentiation of the hypothalamic-pituitary-gonadal axis, and other neuroendocrine systems regulating the thyroid, metabolic, and stress axes and their physiological responses. Weakly estrogenic and anti-androgenic pollutants such as bisphenol A, phthalates, phytochemicals, and the fungicide vinclozolin can lead to severe and widespread neuroendocrine disruptions in discrete brain regions, including the hippocampus, amygdala, and hypothalamus, resulting in behavioral changes in a wide range of species. Behavioral features that have been shown to be affected by one or more these chemicals include cognitive deficits, heightened anxiety or anxiety-like, sociosexual, locomotor, and appetitive behaviors. Neuroactive pharmaceuticals are now widely detected in aquatic environments and water supplies through the release of wastewater treatment plant effluents. The antidepressant fluoxetine is one such pharmaceutical neuroendocrine disruptor. Fluoxetine is a selective serotonin reuptake inhibitor that can affect multiple neuroendocrine pathways and behavioral circuits, including disruptive effects on reproduction and feeding in fish. There is growing evidence for the association between environmental contaminant exposures and diseases with strong neuroendocrine components, for example decreased fecundity, neurodegeneration, and cardiac disease. It is critical to consider the timing of exposures of neuroendocrine disruptors because embryonic stages of central nervous system development are exquisitely sensitive to adverse effects. There is also evidence for epigenetic and transgenerational neuroendocrine disrupting effects of some pollutants. We must now consider the impacts of neuroendocrine disruptors on reproduction, development, growth and behaviors, and the population consequences for evolutionary change in an increasingly contaminated world. This review examines the evidence to date that various so-called neuroendocrine disruptors can induce such effects often at environmentally-relevant concentrations.

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Acute postnatal exposure to di(2-ethylhexyl) phthalate adversely impacts hippocampal development in the male rat

Cited by 73 publications

References 24 publications

Perinatal exposure to di-(2-ethylhexyl) phthalate affects anxiety- and depression-like behaviors in mice

Perinatal exposure to di-(2-ethylhexyl) phthalate affects anxiety- and depression-like behaviors in mice

Maternal exposure to di-(2-ethylhexyl) phthalate exposure deregulates blood pressure, adiposity, cholesterol metabolism and social interaction in mouse offspring

Current concepts in neuroendocrine disruption

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