Alternative models in developmental toxicology

Lee, Hyung-yul; Inselman, Amy L.; Kanungo, Jyotshnabala; Hansen, Deborah K.

doi:10.3109/19396368.2011.648302

Cited by 46 publications

(20 citation statements)

References 78 publications

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“…Combining the BeWo cell layer model with the EST has proven to be a way to predict relative in vivo developmental toxicity [35][36][37]. The EST has been validated by the European Centre for the Validation of Alternative Methods (ECVAM) [38,39], where the differentiation of the mouse embryonic stem cells (mESCs) into beating cardiomyocytes is representing the early stages of embryonic development [40,41]. Only few studies used the EST to examine the developmental toxicity of AgNPs [41].…”

Section: Introductionmentioning

confidence: 99%

Combination of the BeWo b30 placental transport model and the embryonic stem cell test to assess the potential developmental toxicity of silver nanoparticles

et al. 2020

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Background: Silver nanoparticles (AgNPs) are used extensively in various consumer products because of their antimicrobial potential. This requires insight in their potential hazards and risks including adverse effects during pregnancy on the developing fetus. Using a combination of the BeWo b30 placental transport model and the mouse embryonic stem cell test (EST), we investigated the capability of pristine AgNPs with different surface chemistries and aged AgNPs (silver sulfide (Ag 2 S) NPs) to cross the placental barrier and induce developmental toxicity. The uptake/ association and transport of AgNPs through the BeWo b30 was characterized using ICP-MS and single particle (sp)ICP-MS at different time points. The developmental toxicity of the AgNPs was investigated by characterizing their potential to inhibit the differentiation of mouse embryonic stem cells (mESCs) into beating cardiomyocytes. Results: The AgNPs are able to cross the BeWo b30 cell layer to a level that was limited and dependent on their surface chemistry. In the EST, no in vitro developmental toxicity was observed as the effects on differentiation of the mESCs were only detected at cytotoxic concentrations. The aged AgNPs were significantly less cytotoxic, less bioavailable and did not induce developmental toxicity. Conclusions: Pristine AgNPs are capable to cross the placental barrier to an extent that is influenced by their surface chemistry and that this transport is likely low but not negligible. Next to that, the tested AgNPs have low intrinsic potencies for developmental toxicity. The combination of the BeWo b30 model with the EST is of added value in developmental toxicity screening and prioritization of AgNPs.

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Section: Introductionmentioning

confidence: 99%

Combination of the BeWo b30 placental transport model and the embryonic stem cell test to assess the potential developmental toxicity of silver nanoparticles

et al. 2020

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“…Thus, an assessment of developmental effects in zebrafish complement the murine studies. Zebrafish are highly suitable for studies to screen for developmental toxicity and provide several unique advantages for use as a high‐throughput in vivo model system for toxicological assessment (Lee, Inselman, Kanungo, & Hansen, ). Development in zebrafish occurs rapidly in a transparent embryo, and organogenesis is completed within 96 hrs post fertilization (de Souza Anselmo, Sardela, de Sousa, & Pereira, ).…”

Section: Discussionmentioning

confidence: 99%

Safety of bovine milk derived extracellular vesicles used for delivery of RNA therapeutics in zebrafish and mice

Matsuda

Moirangthem

Angom

et al. 2019

J of Applied Toxicology

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Extracellular vesicles are endogenous biological nanoparticles that have potential for use as therapeutic nanoparticles or as delivery vehicles for therapeutic agents.Milk nanovesicles (MNV) are extracellular vesicles isolated from bovine milk that have been explored for use as delivery vehicles for RNA therapeutics such as small interfering RNA (siRNA). We performed in vivo toxicological studies of MNV or therapeutic MNV (tMNV) loaded with siRNA as a prelude to their clinical use.Development toxicity was assessed in zebrafish embryos. Acute toxicity was assessed in both mice and zebrafish whereas safety, biochemical, histological and immune effects after multiple dosing were assessed in mice. Zebrafish embryo hatching was accelerated with MNV and tMNV. While acute toxicity or effects on mortality were not observed in zebrafish, developmental effects were observed at high concentrations of MNV. There was a lack of discernable toxicity, mortality and systemic inflammatory or immunological responses in mice following administration of either MNVs or tMNVs. The tolerability and lack of discernable developmental or systemic in vivo toxicity support their use as biological nanotherapeutics. Adoption of a standardized protocol for systematic analysis of in vivo safety and toxicity will facilitate preclinical assessment of EV based formulations for therapeutic use.

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“…Zebrafish (Danio rerio) is an excellent model to examine the effects of pesticide exposure on development due to external embryo development, large clutch sizes, and transparency of the embryo [18]. Teratogenicity of carbamate exposure in zebrafish embryos is well documented.…”

Section: Introductionmentioning

confidence: 99%

Exposure of Larval Zebrafish to the Insecticide Propoxur Induced Developmental Delays that Correlate with Behavioral Abnormalities and Altered Expression of hspb9 and hspb11

Shields

Hales

Ranspach

et al. 2019

Toxics

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Recent studies suggest that organophosphates and carbamates affect human fetal development, resulting in neurological and growth impairment. However, these studies are conflicting and the extent of adverse effects due to pesticide exposure warrants further investigation. In the present study, we examined the impact of the carbamate insecticide propoxur on zebrafish development. We found that propoxur exposure delays embryonic development, resulting in three distinct developmental stages: no delay, mild delay, or severe delay. Interestingly, the delayed embryos all physically recovered 5 days after exposure, but behavioral analysis revealed persistent cognitive deficits at later stages. Microarray analysis identified 59 genes significantly changed by propoxur treatment, and Ingenuity Pathway Analysis revealed that these genes are involved in cancer, organismal abnormalities, neurological disease, and hematological system development. We further examined hspb9 and hspb11 due to their potential roles in zebrafish development and found that propoxur increases expression of these small heat shock proteins in all of the exposed animals. However, we discovered that less significant increases were associated with the more severely delayed phenotype. This raises the possibility that a decreased ability to upregulate these small heat shock proteins in response to propoxur exposure may cause embryos to be more severely delayed.

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Alternative models in developmental toxicology

Cited by 46 publications

References 78 publications

Combination of the BeWo b30 placental transport model and the embryonic stem cell test to assess the potential developmental toxicity of silver nanoparticles

Combination of the BeWo b30 placental transport model and the embryonic stem cell test to assess the potential developmental toxicity of silver nanoparticles

Safety of bovine milk derived extracellular vesicles used for delivery of RNA therapeutics in zebrafish and mice

Exposure of Larval Zebrafish to the Insecticide Propoxur Induced Developmental Delays that Correlate with Behavioral Abnormalities and Altered Expression of hspb9 and hspb11

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