Allogeneic murine pregnancy models for assessing the developmental effects of immune-stimulating antibodies: Challenges in reproducibility.

Literature suggests that murine allogeneic pregnancy models are an alternative approach for evaluating the developmental toxicity of immune-stimulating agents. In this study, multiple syngeneic and allogeneic murine pregnancy models were used to assess the potential embryo-fetal effects of four different murine antibodies (IgG or IgG ) that activate the immune system by binding to T-cell receptors (PD-L1, LAG-3, and GITR). The pregnancy models were generated by within and between matings of five different inbred strains of mice (CBA/CaJ, DBA/2J, BALB/c, C57BL/6, and CBA/J).

Morphological score assignment guidelines for the dechorionated zebrafish teratogenicity assay.

Background: Recently we reported the development and optimization of a zebrafish teratogenicity assay using dechorionated AB strain embryos, a promising assay that was 87% concordant in correctly identifying in vivo teratogens and non-teratogens from a set of 31 compounds (Brannen et al., 2010: Birth Defects Res 89:66-77).

Methods: This assay utilizes a zebrafish morphological score system to characterize adverse effects and identify the no-observed-adverse-effect level (NOAEL).

Development of a zebrafish embryo teratogenicity assay and quantitative prediction model.

Background: A zebrafish (Danio rerio) teratogenicity assay has been developed and evaluated for its ability to predict the teratogenic potential of chemicals.

Methods: Zebrafish embryos were dechorionated and then exposed to a test solution from 4-6 hours post-fertilization, and embryos or larvae were assessed up to 5 days post-fertilization (dpf) for viability and morphology. In preliminary experiments, the potential time points for assessment of compound-induced dysmorphology and general toxicity parameters were evaluated, and 5 dpf was found to be the optimum developmental stage for evaluation.