Stage-specific signaling pathways during murine testis development and spermatogenesis: A pathway-based analysis to quantify developmental dynamics

Shifting the field of developmental toxicology toward evaluation of pathway perturbation requires a quantitative definition of normal developmental dynamics. This project examined a publicly available dataset to quantify pathway dynamics during testicular development and spermatogenesis and anchor toxicant-perturbed pathways within the context of normal development. Genes significantly changed throughout testis development in mice were clustered by their direction of change using K-means clustering. Gene Ontology terms enriched among each cluster were identified using MAPPfinder. Temporal pathway dynamics of enriched terms were quantified based on average expression intensity for all genes associated with a given term. This analysis captured processes that drive development, including the peak in steroidogenesis known to occur around gestational day 16.5 and the increase in meiosis and spermatogenesis-related pathways during the first wave of spermatogenesis. Our analysis quantifies dynamics of pathways vulnerable to toxicants and provides a framework for quantifying perturbation of these pathways.