Effects and underlying cellular pathway involved in the impairment of the neurovascular unit following exposure of adult male mice to low doses of di(2-ethylhexyl) phthalate alone or in an environmental phthalate mixture

Ahmadpour, Delnia; Mhaouty-Kodja, Sakina; Grange-Messent, Valérie

doi:10.1016/j.envres.2021.112235

Cited by 9 publications

(12 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An interesting result regarding the effects of adult exposure to phthalates at low doses in the hypothalamus and hippocampus is disruption of the BBB integrity associated with increased glial activation and/ or neuroinflammatory processes [34,35]. In the field of environmental toxicology in general and endocrine disruption in particular, physiological barriers including the BBB are considered mainly for the passage of substances and less for the impact of chemical substances on their integrity.…”

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

View full text Add to dashboard Cite

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.

show abstract

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

View full text Add to dashboard Cite

show abstract

“…DEHP concentrations in developed urban soils can reach 264 mg/kg . DEHP at low-dose exposure affects neurovascular conjugates in mice . MPs account for by far the largest number of marine debris .…”

Section: Discussionmentioning

confidence: 99%

“…44 DEHP at low-dose exposure affects neurovascular conjugates in mice. 45 MPs account for by far the largest number of marine debris. 46 The intake of MPs causes stomach damage and inflammation in mice and increases the risk of cancer in both animals and humans.…”

Section: Dehp and Mps Evoke Oxidative Stress And Induce Antioxidant C...mentioning

confidence: 99%

Di-(2-Ethylhexyl) Phthalate and Microplastics Induced Neuronal Apoptosis through the PI3K/AKT Pathway and Mitochondrial Dysfunction

Zhang

Sun

et al. 2022

J. Agric. Food Chem.

View full text Add to dashboard Cite

Di-(2-Ethylhexyl) phthalate (DEHP) and microplastics (MPs) have released widespread residues to the environment and possess the ability to cause damage to humans and animals. However, there are still gaps in the study of damage to neurons caused by DEHP and MPs in mice cerebra and whether they have combined toxic effects. To investigate the underlying mechanism of action, mice were fed 200 mg/kg DEHP and 10 mg/L MPs in vivo. In vitro, NS20Y (CBNumber: CB15474825) cells were treated with 25 μM DEHP and 775 mg/L MPs. Next, qRT-PCR and western blot analysis were performed to evaluate PI3K/AKT pathway genes, mitochondrial dynamics-related genes, apoptosis-related genes, and GSK-3β and its associated genes, mRNA, and protein expression. To determine pathological changes in the mice cerebra, hematoxylin and eosin (H&E) staining, transmission electron microscopy, and TUNEL staining were employed. To determine the levels of reactive oxygen species (ROS) and apoptosis cells in vitro, ROS staining, acridine orange/ethidium bromide (AO/EB) staining, and flow cytometry were performed. Our results demonstrated that DEHP and MPs caused changes in mitochondrial function, and GSK-3β and its associated gene expression in mice through the PI3K/AKT pathway, which eventually led to apoptosis of neurons. Moreover, our findings showed that DEHP and MPs have a combined toxic effect on mice cerebra. Our findings facilitate the understanding of the neurotoxic effects of DEHP and MPs on neurons in the cerebra of mice and help identify the important role of maintaining normal mitochondrial function in protecting cerebrum health.

show abstract

“…Finally, adulthood is still an underestimated period of exposure with only a few studies analyzing the effects induced by phthalate exposure in adult females ( Figure 2 ). Previous studies showed that the adult brain can also be impacted by endocrine disruptors including phthalates in both sexes [ 4 , 5 , 94 , 95 , 96 , 97 , 98 ]. Given the critical role of several brain regions in the regulation of female behaviors and the potential transgenerational effects of many chemical substances including phthalates on descendants, adulthood should be studied as much as the developmental periods.…”

Section: Discussionmentioning

confidence: 99%

Behavioral Effects of Exposure to Phthalates in Female Rodents: Evidence for Endocrine Disruption?

Adam

Mhaouty-Kodja

2022

IJMS

Self Cite

View full text Add to dashboard Cite

Phthalates have been widely studied for their reprotoxic effects in male rodents and in particular on testosterone production, for which reference doses were established. The female rodent brain can also represent a target for exposure to these environmental endocrine disruptors. Indeed, a large range of behaviors including reproductive behaviors, mood-related behaviors, and learning and memory are regulated by sex steroid hormones. Here we review the experimental studies addressing the effects and mechanisms of phthalate exposure on these behaviors in female rodents, paying particular attention to the experimental conditions (period of exposure, doses, estrous stage of analyses etc.). The objective of this review is to provide a clear picture of the consistent effects that can occur in female rodents and the gaps that still need to be filled in terms of effects and mode(s) of action for a better risk assessment for human health.

show abstract

Effects and underlying cellular pathway involved in the impairment of the neurovascular unit following exposure of adult male mice to low doses of di(2-ethylhexyl) phthalate alone or in an environmental phthalate mixture

Cited by 9 publications

References 54 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

Di-(2-Ethylhexyl) Phthalate and Microplastics Induced Neuronal Apoptosis through the PI3K/AKT Pathway and Mitochondrial Dysfunction

Behavioral Effects of Exposure to Phthalates in Female Rodents: Evidence for Endocrine Disruption?

Contact Info

Product

Resources

About