Primary neuronal-astrocytic co-culture platform for neurotoxicity assessment of di-(2-ethylhexyl) phthalate

Wu, Yang; Li, Ké; Zuo, Haoxiao; Yuan, Ye; Sun, Yi; Yang, Xu

doi:10.1016/s1001-0742(13)60504-5

Cited by 30 publications

(22 citation statements)

References 29 publications

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“…DEHP-dependent ROS production is well-described in different culture models, mainly in relation to the reproductive system. Our data can be compared with the only relevant paper in which DEHP-dependent ROS production in in vitro neuron-astrocyte co-cultures has been studied (Wu et al 2014 ). The data presented by Wu et al ( 2014 ) demonstrated that even 1 nM DEHP caused a significant increase in ROS concentrations, indicating that neuronal-astrocyte co-cultures are more sensitive to DEHP than cerebral cell mono-cultures, as is also evident in our experiments.…”

Section: Discussionmentioning

confidence: 98%

“…Recently, Wu et al ( 2014 ) reported that 1 nM DEHP significantly increased ROS production in neuron-astrocyte co-cultures isolated from Balb/c mice and postulated what the cell-dependent effects were (Wu et al 2014 ). Because of the interactions between ROS and AhR signaling in neuronal cells (Szychowski et al 2016 ), the present study aimed to investigate the effects of DEHP on ROS production; AhR, Cyp1a1 and Cyp1b1 mRNA, and protein expression; and Cyp1a1-related EROD activity in mouse cortical neurons and glial cells in vitro.…”

Section: Introductionmentioning

confidence: 99%

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The Action of Di-(2-Ethylhexyl) Phthalate (DEHP) in Mouse Cerebral Cells Involves an Impairment in Aryl Hydrocarbon Receptor (AhR) Signaling

et al. 2018

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Di-(2-ethylhexyl) phthalate (DEHP) is used as a plasticizer in various plastic compounds, such as polyvinyl chloride (PVC), and products including baby toys, packaging films and sheets, medical tubing, and blood storage bags. Epidemiological data suggest that phthalates increase the risk of the nervous system disorders; however, the impact of DEHP on the brain cells and the mechanisms of its action have not been clarified. The aim of the present study was to investigate the effects of DEHP on production of reactive oxygen species (ROS) and aryl hydrocarbon receptor (AhR), as well as Cyp1a1 and Cyp1b1 mRNA and protein expression in primary mouse cortical neurons and glial cells in the in vitro mono-cultures. Our experiments showed that DEHP stimulated ROS production in both types of mouse neocortical cells. Moreover, the results strongly support involvement of the AhR/Cyp1A1 signaling pathway in the action of DEHP in neurons and glial cells. However, the effects of DEHP acting on the AhR signaling pathways in these two types of neocortical cells were different. In neurons, AhR mRNA expression did not change, but AhR protein expression decreased in response to DEHP. A similar trend was observed for Cyp1a1 and Cyp1b1 mRNA and protein expression. Failure to induce Cyp1a1 in neurons was confirmed by EROD assay. In primary glial cells, a decrease in AhR protein level was accompanied by a decrease in AhR mRNA expression. In glial cells, mRNA and protein expression of Cyp1a1 as well as Cyp1a1-related EROD activity were significantly increased. As for Cyp1b1, both in neurons and glial cells Cyp1b1 mRNA expression did not significantly change, whereas Cyp1b1 protein level were decreased. We postulate that developmental exposure to DEHP which dysregulates AhR/Cyp1a1 may disrupt defense processes in brain neocortical cells that could increase their susceptibility to environmental toxins.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

The Action of Di-(2-Ethylhexyl) Phthalate (DEHP) in Mouse Cerebral Cells Involves an Impairment in Aryl Hydrocarbon Receptor (AhR) Signaling

et al. 2018

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“…Mitochondrial respiration produces a significant amount of ROS, this process, if unregulated, can damage sperm genomic DNA, lipid and protein structures, and subsequently impair sperm integrity and fertility. Previous reports show that DEHP exposed oocytes and somatic cells produce an excessive amount of ROS via mitochondrial-derived ROS (Rosado-Berrios, Vélez, and Zayas 2011; Roth 2018; Wu et al 2014). However, it has not been shown that DEHP affects spermatozoa in a similar manner.…”

Section: Discussionmentioning

confidence: 96%

“…There are two main ways in which sperm can encounter unmetabolized DEHP: via abrupt release from adipose tissue or through release from medical devices, such as a urological catheter-making unmetabolized DEHP a prominent threat to sperm fertility. DEHP exposure has been previously linked to increased ROS production in somatic cells and oocytes (Wu et al 2014;Tripathi et al 2019;Kim et al 2013;Ambruosi et al 2011). However, its impact on ROS over-production in sperm was not elucidated.…”

Section: Discussionmentioning

confidence: 99%

The impact of di-2-ethylhexyl phthalate on sperm fertility

Khasin

Rosa

Petersen

et al. 2020

Preprint

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A growing number of studies point to reduced fertility upon chronic exposure to endocrine-disrupting chemicals (EDCs) such as phthalates and plasticizers. These toxins are ubiquitous and are often found in food and beverage containers, medical devices, as well as in common household and personal care items. Animal studies with EDCs, such as phthalates and bisphenol A have shown a dose-dependent decrease in fertility and embryo toxicity upon chronic exposure. However, limited research has been conducted on the acute effects of these EDCs on male fertility. Here we used a murine model to test the acute effects of four ubiquitous environmental toxins: bisphenol A (BPA), di-2-ethylhexyl phthalate (DEHP), diethyl phthalate (DEP), and dimethyl phthalate (DMP) on sperm fertilizing ability and pre-implantation embryo development. The most potent of these toxins, di-2ethylhexyl phthalate (DEHP), was further evaluated for its effect on sperm ion channel activity, capacitation status, acrosome reaction and generation of reactive oxygen species (ROS). DEHP demonstrated a profound hazardous effect on sperm fertility by producing an altered capacitation profile, impairing the acrosome reaction, and, interestingly, also increasing ROS production. These results indicate that in addition to its known chronic impact on reproductive potential, DEHP also imposes acute and profound damage to spermatozoa, and thus, represents a significant risk to male fertility.

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“…Wu ve ark.nın, primer nöron-astrosit ko-kültüründe yaptıkları bir çalışmada, DEHP'nin doza bağlı olarak ROS düzeylerini artır-dığı bulunmuştur. 62 Kim ve ark.nın yaptığı çalışmada neonatal fare serebellumundan izole edilen multipotent nöral kök hücreler kullanılarak BPA'nın nöron farklılaş-ması ve hipokampal nörogenez üzerine etkileri araştırılmıştır. BPA'nın yüksek konsantrasyonlarda (400-500 µM) hücre proliferasyonunu azalttığı gö-rülmüştür.…”

Section: Hücre Kültürü çAlişmalariunclassified

The Neuroendocrine and Neurodevelopmental Effects of Endocrine Disrupting Chemicals

Yirün¹,

Erkekoğlu²,

Koçer-Gümüşel³

2018

Turkiye Klinikleri J Neur

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Ö ÖZ ZE ET T Yaşamın değişik dönemlerinde endokrin bozucu kimyasal madde (EBK)'lere maruziyet, organizmada santral sinir sistemi dahil olmak üzere pek çok sistem üzerinde istenmeyen etkilere yol açabilmektedir. Özellikle anne karnındaki maruziyet ile çocukluk dönemindeki maruziyetin etkilerinin çok daha önemli olabileceği ve ciddi sonuçlara yol açabileceği üzerinde durulmaktadır. Son yıllarda, EBK'lere temas ile bilişsel eksiklikler, yavaş nörogelişim, agresyon ve depresyon insidansında artış, hiperaktivite ve dikkat sorunlarını ilişkilendiren çalışmalar bulunmaktadır. Santral sinir sistemi tüm nörotransmitter, nöropeptit ve nörohormon sistemleri ile denge durumunda işlemek-tedir. EBK'ler mevcut duygudurum dengesini bozarak duygusal, sosyal, davranışsal değişimlere veya nörodejeneratif hasarlara, öğrenme ve hafıza bozukluklarına neden olabilmektedirler. Maruziyetin sonuçları maruz kalınan doza, maruziyet zamanına ve maruz kalınan maddenin karakteristik özel-liklerine göre değişim göstermektedir. Nöronal hasarlar özellikle sinir sisteminin gelişme dönem-lerinde meydana gelen maruziyetlerde daha belirgin olmaktadır. Belirtiler (öğrenme güçlüğü, otizm, dikkat eksikliği, hiperaktivite, nörodejeneratif hastalıklar) çoğunlukla birden fazla mekanizmanın birlikte etkilenmesiyle ortaya çıkmakta ve özellikle karışım hâlinde EBK'lere maruziyet sonucunda daha belirgin etkiler oluşabileceği öngörülebilmektedir. Bu çalışmada, çevrede çok yaygın olarak bulunan ve endokrin bozucu etkileri bilinen bisfenol A ve ftalatların nöroendokrin sistem ve nöro-gelişim üzerindeki toksik etkilerinin incelenmesi amaçlanmıştır.A An na ah h t ta ar r K Ke e l li i m me e l le er r: : Bisfenol A; nörodavranış; nöroendokrin bozucu; nörogelişim; ftalatlar; cinsel dimorfizm A AB BS S T TR RA AC CT T Endocrine disrupting chemicals (EDCs) can cause undesirable effects on many systems, including the central nervous system, in exposed organisms at different periods of life. It can be emphasized that the effects of maternal and childhood exposure may be more important and may lead to serious consequences. In recent years, EDC exposure has been associated with cognitive deficits, slow neurodevelopment, increased incidence of aggression and depression, hyperactivity and attention problems. The central nervous system operates in balance with all neurotransmitters, neuropeptide and neurohormone systems. EDCs may cause emotional, social and behavioral changes or neurodegenerative damage, learning and memory disorders by disturbing the current state of mood balance. The results of EDC exposure vary according to dose, time of exposure and the characteristics of the substance. Neuronal damage is more pronounced in exposures that occur during the developmental stages of the nervous system. Symptoms (learning disability, autism, attention deficit, hyperactivity, neurodegenerative diseases) are often the consequences of multiple mechanisms being affected together, and it can be suggested that symptoms may be more significant, particularly as a result of exposure ...

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Primary neuronal-astrocytic co-culture platform for neurotoxicity assessment of di-(2-ethylhexyl) phthalate

Cited by 30 publications

References 29 publications

The Action of Di-(2-Ethylhexyl) Phthalate (DEHP) in Mouse Cerebral Cells Involves an Impairment in Aryl Hydrocarbon Receptor (AhR) Signaling

The Action of Di-(2-Ethylhexyl) Phthalate (DEHP) in Mouse Cerebral Cells Involves an Impairment in Aryl Hydrocarbon Receptor (AhR) Signaling

The impact of di-2-ethylhexyl phthalate on sperm fertility

The Neuroendocrine and Neurodevelopmental Effects of Endocrine Disrupting Chemicals

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