Fluoxetine Inhibits Canonical Wnt Signaling to Impair Embryoid Body Morphogenesis: Potential Teratogenic Mechanisms of a Commonly Used Antidepressant.

Fluoxetine is one of the most commonly prescribed antidepressants in the selective serotonin reuptake inhibitor (SSRI) class. Epidemiologic studies have suggested a link between maternal fluoxetine use during pregnancy and an increased incidence of birth defects. However, the mechanisms by which fluoxetine adversely impacts embryonic developments are unknown.

Exposure-Based Validation of an In Vitro Gastrulation Model for Developmental Toxicity Assays.

Establishment of effective non-animal alternatives for developmental toxicity screening assays is desirable to ensure maternal and fetal health outcomes. Validation of such assays requires a comparison between the in vitro responses to chemical exposures and the in vivo impacts of the corresponding compounds at equivalent concentrations. Here, we investigated how the P19C5 gastrulation model responds to 24 compounds at specific concentrations, some of which are categorized as positive exposures based on previously observed detrimental effects on development in vivo, whereas others are categorized as negative exposures due to lack of effects in vivo.

Use of In Vitro Morphogenesis of Mouse Embryoid Bodies to Assess Developmental Toxicity of Therapeutic Drugs Contraindicated in Pregnancy.

In utero exposure to certain chemicals can impair embryo development, causing embryonic death, growth retardation, or severe birth defects. Establishment of effective in vitro tests is crucial for identifying developmental toxicants and for reducing the financial and ethical burden of animal-based tests. Previously, we created an in vitro morphogenesis model using pluripotent P19C5 mouse embryonal carcinoma stem cells that mimics the process of gastrulation and axial body elongation of embryos.