Molecular Evaluation of Impacted Reproductive Physiology in Fathead Minnow Testes Provides Mechanistic Insights into Insensitive Munitions Toxicology.

•Chronic (21d) exposure to high NTO exposure concentrations (≥ 383 mg/L) elicited impacts on reproductive physiology in testes of adult fathead minnows.•Transcriptomics analysis identified significant enrichment of steroid metabolism pathways, mTORC-signal control of spermatogonia differentiation, and sperm-associated antigen 6 (Spag6) in NTO which have logical connections to reduced spermatozoa.•Chronic (21d) exposure to the IMX-101 formulation elicited significant mortality at the two highest exposure concentrations of 25.2 and 50.9 mg/L (DNAN nominal + NTO measured + NQ measured).•The 12.6 mg/L IMX-101 exposure caused significant sublethal impacts on testes including sperm necrosis, interstitial fibrosis, and Sertoli-like cell hyperplasia.•Transcriptional profiles for IMX-101 indicated significant enrichment of multiple signaling pathways supporting spermatogenesis and sperm flagellar structure, as well as increases within the PPARα-RXRα pathway having logical connections to Sertoli cell hyperplasia.