Establishment of a developmental neurotoxicity test by Sox1-GFP mouse embryonic stem cells

Park, Seon Mi; Jo, Na Rae; Lee, Bonn; Jung, Eui‐Man; Lee, Sung Duck; Jeung, Eui‐Bae

doi:10.1016/j.reprotox.2021.07.004

Cited by 7 publications

(3 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The developmental neurotoxicity of D5 was evaluated using the DNT method [19]. This method supported the results from in vivo tests that D5 has neurotoxicity.…”

Section: Discussionmentioning

confidence: 80%

Effects of Maternal Exposure to Decamethylcyclopentasiloxane on the Alternations in Offspring Behaviors in Mice

Kim

Lee

et al. 2022

Biomedicines

Self Cite

View full text Add to dashboard Cite

D5, a member of the cyclic siloxane family, is widely used in personal care products such as shampoo, cosmetics, and deodorant and as an industrial intermediate. D5 can mainly be absorbed orally or through inhalation. Through these routes, people are exposed to D5 daily. However, the risk of prenatal exposure to D5 has not been fully elucidated. In this study, the effect of D5 on neural development was established through behavioral tests on offspring mice. The result confirmed that the maternal administration of 12 mg/kg of D5 showed depression in tail suspension and decreased performance in the forced swimming test as well as an increase in repetitive activity in both the marble-burying test and grooming test compared to the vehicle group. Furthermore, the 12 mg/kg group showed a decrease in cognitive ability and social behavior in the three-chamber test. In the novel object recognition test, memory impairment and a lack of exploring ability were found in the 12 mg/kg group. In conclusion, it is suggested that maternal D5 exposure has developmental neurotoxicity and can cause behavioral disorders in the offspring of mice. Thus, the usage of D5 needs to be considered carefully.

show abstract

“…The developmental neurotoxicity of D5 was evaluated using the DNT method [19]. This method supported the results from in vivo tests that D5 has neurotoxicity.…”

Section: Discussionmentioning

confidence: 80%

Effects of Maternal Exposure to Decamethylcyclopentasiloxane on the Alternations in Offspring Behaviors in Mice

Kim

Lee

et al. 2022

Biomedicines

Self Cite

View full text Add to dashboard Cite

show abstract

“…During motor neuron formation, there are several well-studied markers that can be used to follow the time course of differentiation, including SOX1 , NES , OLIG2, and CHAT. The transcription factor Sox1 is the earliest and most specific marker for neuroepithelial cells, as it is expressed by progenitor cells in the nervous system during fetal neurodevelopment [ 66 , 67 ]. Nestin is an intermediate filament protein, encoded by the NES gene, which is highly expressed in multipotent stem cells and neural progenitor cells of the developing brain [ 68 , 69 ].…”

Section: Discussionmentioning

confidence: 99%

Arsenic Impairs Differentiation of Human Induced Pluripotent Stem Cells into Cholinergic Motor Neurons

Perego,

McMichael,

McMurry

et al. 2023

Toxics

View full text Add to dashboard Cite

Arsenic exposure during embryogenesis can lead to improper neurodevelopment and changes in locomotor activity. Additionally, in vitro studies have shown that arsenic inhibits the differentiation of sensory neurons and skeletal muscle. In the current study, human-induced pluripotent stem (iPS) cells were differentiated into motor neurons over 28 days, while being exposed to up to 0.5 μM arsenic. On day 6, neuroepithelial progenitor cells (NEPs) exposed to arsenic had reduced transcript levels of the neural progenitor/stem cell marker nestin (NES) and neuroepithelial progenitor marker SOX1, while levels of these transcripts were increased in motor neuron progenitors (MNPs) at day 12. In day 18 early motor neurons (MNs), choline acetyltransferase (CHAT) expression was reduced two-fold in cells exposed to 0.5 μM arsenic. RNA sequencing demonstrated that the cholinergic synapse pathway was impaired following exposure to 0.5 μM arsenic, and that transcript levels of genes involved in acetylcholine synthesis (CHAT), transport (solute carriers, SLC18A3 and SLC5A7) and degradation (acetylcholinesterase, ACHE) were all downregulated in day 18 early MNs. In day 28 mature motor neurons, arsenic significantly downregulated protein expression of microtubule-associated protein 2 (MAP2) and ChAT by 2.8- and 2.1-fold, respectively, concomitantly with a reduction in neurite length. These results show that exposure to environmentally relevant arsenic concentrations dysregulates the differentiation of human iPS cells into motor neurons and impairs the cholinergic synapse pathway, suggesting that exposure impairs cholinergic function in motor neurons.

show abstract

“…The expression levels of the genes were compared quantitatively using the ∆∆Ct method with 18S as the endogenous control for expression. Details of the experimental method can be found elsewhere [ 32 ]. For statistical confidence, the Ct values were obtained from the triplicate average.…”

Section: Methodsmentioning

confidence: 99%

Effects of Sodium Arsenite on the Myocardial Differentiation in Mouse Embryonic Bodies

Jeong

Ahn

Kwon

et al. 2023

Toxics

Self Cite

View full text Add to dashboard Cite

Arsenic in inorganic form is a known human carcinogen; even low levels of arsenic can interfere with the endocrine system. In mammalian development, arsenic exposure can cause a malformation of fetuses and be lethal. This study examined the effects of sodium arsenite (SA) as the inorganic form of arsenic in embryonic bodies (EBs) with three germ layers in the developmental stage. This condition is closer to the physiological condition than a 2D cell culture. The SA treatment inhibited EBs from differentiating into cardiomyocytes. A treatment with 1 μM SA delayed the initiation of beating, presenting successful cardiomyocyte differentiation. In particular, mitochondria function analysis showed that SA downregulated the transcription level of the Complex IV gene. SA increased the fission form of mitochondrion identified by the mitochondria number and length. In addition, a treatment with D-penicillamine, an arsenic chelator, restored the beat of EBs against SA, but not mitochondrial dysfunction. These findings suggest that SA is a toxicant that induces mitochondrial damage and interferes with myocardial differentiation and embryogenesis. This study suggests that more awareness of SA exposure during pregnancy is required because even minuscule amounts have irreversible adverse effects on embryogenesis through mitochondria dysfunction.

show abstract

Establishment of a developmental neurotoxicity test by Sox1-GFP mouse embryonic stem cells

Cited by 7 publications

References 28 publications

Effects of Maternal Exposure to Decamethylcyclopentasiloxane on the Alternations in Offspring Behaviors in Mice

Effects of Maternal Exposure to Decamethylcyclopentasiloxane on the Alternations in Offspring Behaviors in Mice

Arsenic Impairs Differentiation of Human Induced Pluripotent Stem Cells into Cholinergic Motor Neurons

Effects of Sodium Arsenite on the Myocardial Differentiation in Mouse Embryonic Bodies

Contact Info

Product

Resources

About