Assessing early-stage teratogenic exposure using the Embryonic Pattern Checklist
July 12
Introduction: Early teratogenic insults exert broad and persistent consequences on subsequent morphogenesis, yet few investigations monitor embryos immediately after exposure. Most reports isolate a single developmental defect and fail to capture the global impact of perturbation.
Methods: We employed the Embryonic Pattern Checklist (EPC) to survey structural and bioelectric anomalies in a more integrative manner. Thirty-two embryos subjected to a defined teratogenic regimen (TE group) and twenty-nine stage-matched unperturbed embryos (UE group) were scored with the EPC-St1–St18 version. Group comparisons across eight subscales—axial alignment, left-right asymmetry, germ-layer integrity, organ rudiment specification, proliferation rate, apoptosis mapping, surface Vmem gradients, and extracellular matrix deposition—were performed. Receiver Operating Characteristic (ROC) analyses quantified classification performance. Finally, sensitive window and agent-type analyses were executed with reference to detailed exposure timelines.
Results: The TE cohort displayed significantly elevated disruption in seven of the eight subscales. Logistic regression incorporating every combination of EPC subscale Z-scores plus developmental stage, somite count, and strain background yielded 2047 models, each subjected to ROC analysis. Three representative models emerged: the highest-accuracy model (EPC Z-scores + stage + strain; sensitivity 0.906, specificity 0.966), a model omitting strain (sensitivity 0.875, specificity 0.931), and a morphology-only model (sensitivity 0.906, specificity 0.862). Thus, EPC profiling alone afforded strong predictive power for prior teratogenic exposure using purely morphologic and bioelectric readouts, without direct chemical measurement. Sensitive-window analysis revealed that exposure during late gastrulation predicted subsequent “axial alignment” and “neuroectoderm pattern” defects, while exposure between late gastrulation and early neurulation predicted “surface Vmem gradient” anomalies. Regarding agent type, oxidative teratogens predicted “apoptosis mapping” and “extracellular matrix” disruptions, whereas mechanical compression predicted “left-right asymmetry” and “proliferation rate” abnormalities.
Conclusion: Teratogen-exposed embryos exhibit a broad spectrum of patterning disturbances that must be considered when designing rescue or regenerative protocols. Insights gleaned from temporal and agent-specific analyses will aid developmental biologists in tailoring targeted interventions to restore normal morphogenesis.