Cerebral concentration and toxicity of endocrine disrupting chemicals: The implication of blood-brain interfaces

Denuzière, Anne; Ghersi‐Egea, Jean‐François

doi:10.1016/j.neuro.2022.04.004

Cited by 17 publications

(3 citation statements)

References 161 publications

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“…The BBB has endocrine properties through response to endocrine systems and secretion of endocrine molecules [44], and it is also considered a key component and perhaps an initiating trigger of neurological and psychiatric disorders [45]. This suggests that BBB integrity should be one of the key targets to assess for the impact of adult exposure to phthalates or other endocrine-disrupting compounds on the nervous system [46]. Much remains to be done concerning evaluation of exposure to phthalates on the developing BBB, which is not only present in the developing brain but must play a key protecting role in the developmental exposure of the brain to chemical substances [47, 48].…”

Section: Discussionmentioning

confidence: 99%

Exposure to Low Doses of Phthalates in Male Rodents: Effects on Reproductive and Cognitive Behaviors

Ducroq,

Grange-Messent,

Mhaouty-Kodja

2023

Neuroendocrinology

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The nervous system is a sensitive target for exposure to environmental endocrine-disrupting compounds (EDC). This vulnerability is particularly important during the critical windows of development and puberty and lasts even at later stages of life. Among these environmental EDC, phthalates have largely been described for their neurotoxic effects. These effects have been reported for a large majority of studies using high to very-high doses of these substances, which are not relevant for environmental exposure. The aim of this review is to analyze specifically the male rodent studies using low doses of phthalates. This analysis focuses on reproductive and cognitive behaviors, given the described anti-androgenic effects of phthalates and the known regulation of these behaviors by sex steroids. We also analyze the other neural effects in the hypothalamus and hippocampus, the brain regions governing these behaviors. A particular focus is on the neurovascular unit, which is newly investigated in the field of endocrine disruption.

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Section: Discussionmentioning

confidence: 99%

Exposure to Low Doses of Phthalates in Male Rodents: Effects on Reproductive and Cognitive Behaviors

Ducroq,

Grange-Messent,

Mhaouty-Kodja

2023

Neuroendocrinology

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“…The fact that TBBPA is a neurotoxicant has been questioned because the blood brain barrier (BBB) is a potent molecular filter protecting the central nervous system ( Kacew and Hayes, 2020 ; Zhou et al, 2020 ; Denuzière and Ghersi-Egea, 2022 ). Nonetheless, the BBB is slightly leaky at two locations in the central nervous system: the choroid plexus at hypocampus, and the median eminence at the root of the hypothalamus.…”

Section: Discussionmentioning

confidence: 99%

Tetrabromobisphenol A effects on differentiating mouse embryonic stem cells reveals unexpected impact on immune system

2022

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Tetrabromobisphenol A (TBBPA) is a potent flame retardant used in numerous appliances and a major pollutant in households and ecosystems. In vertebrates, it was shown to affect neurodevelopment, the hypothalamic-pituitary-gonadal axis and thyroid signaling, but its toxicity and modes of actions are still a matter of debate. The molecular phenotype resulting from exposure to TBBPA is only poorly described, especially at the level of transcriptome reprogramming, which further limits our understanding of its molecular toxicity. In this work, we combined functional genomics and system biology to provide a system-wide description of the transcriptomic alterations induced by TBBPA acting on differentiating mESCs, and provide potential new toxicity markers. We found that TBBPA-induced transcriptome reprogramming affect a large collection of genes loosely connected within the network of biological pathways, indicating widespread interferences on biological processes. We also found two hotspots of action: at the level of neuronal differentiation markers, and surprisingly, at the level of immune system functions, which has been largely overlooked until now. This effect is particularly strong, as terminal differentiation markers of both myeloid and lymphoid lineages are strongly reduced: the membrane T cell receptor (Cd79a, Cd79b), interleukin seven receptor (Il7r), macrophages cytokine receptor (Csf1r), monocyte chemokine receptor (Ccr2). Also, the high affinity IgE receptor (Fcer1g), a key mediator of allergic reactions, is strongly induced. Thus, the molecular imbalance induce by TBBPA may be stronger than initially realized.

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“…In the following sections we will evaluate the current data regarding two environmental contaminants of immediate and emerging concern that may enter brain tissue: per- and polyfluorinated substances (PFAS) and bisphenols. The developmental neurotoxicity of these chemicals are reviewed elsewhere ( Mariussen, 2012 ; O'Shaughnessy et al, 2021 ; Denuziere and Ghersi-Egea, 2022 ; Welch and Mulligan, 2022 ), along with other environmental pollutants such as metals and pesticides ( Ek et al, 2012 ).…”

Section: Contaminants Of Immediate and Emerging Concern That May Cros...mentioning

confidence: 99%

The development and function of the brain barriers – an overlooked consideration for chemical toxicity

Bell

O’Shaughnessy²

2022

Front. Toxicol.

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It is well known that the adult brain is protected from some infections and toxic molecules by the blood-brain and the blood-cerebrospinal fluid barriers. Contrary to the immense data collected in other fields, it is deeply entrenched in environmental toxicology that xenobiotics easily permeate the developing brain because these barriers are either absent or non-functional in the fetus and newborn. Here we review the cellular and physiological makeup of the brain barrier systems in multiple species, and discuss decades of experiments that show they possess functionality during embryogenesis. We next present case studies of two chemical classes, perfluoroalkyl substances (PFAS) and bisphenols, and discuss their potential to bypass the brain barriers. While there is evidence to suggest these pollutants may enter the developing and/or adult brain parenchyma, many studies suffer from confounding technical variables which complicates data interpretation. In the future, a more formal consideration of brain barrier biology could not only improve understanding of chemical toxicokinetics but could assist in prioritizing environmental xenobiotics for their neurotoxicity risk.

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Cerebral concentration and toxicity of endocrine disrupting chemicals: The implication of blood-brain interfaces

Cited by 17 publications

References 161 publications

Exposure to Low Doses of Phthalates in Male Rodents: Effects on Reproductive and Cognitive Behaviors

Exposure to Low Doses of Phthalates in Male Rodents: Effects on Reproductive and Cognitive Behaviors

Tetrabromobisphenol A effects on differentiating mouse embryonic stem cells reveals unexpected impact on immune system

The development and function of the brain barriers – an overlooked consideration for chemical toxicity

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