BackgroundThe use of phytosanitary products is always associated with their safety concern on the environment and on health. The associated adverse effects are very broad and substance-dependent. Among these substances, epoxiconazole (EPOX) is one of the most widely used fungicides, especially in beet crops. Although its use is questionable or even prohibited in the European Union, it is still widely used and its consequences (transgenerational effects) on future generations is unknown.ObjectivesWe aimed to investigate the hepatic effects of epoxiconazole in the descendants of perinatally exposed low-dose C57Bl/6J mice, focusing on liver histological and transcriptomic analyses.MethodsFrom day 0 of gestation up to day 21 postnatal, only pregnant F0 C57BL6/J mice were exposed to EPOX (1.75 μg/kg bw/day). F1 males and females were mated to obtain the F2 generation and similarly, F2 mice were crossed to obtain F3. Histological and transcriptomic analyses of the liver were performed. Gene set enrichment analysis was realized to determine an a priori defined set of genes with significantly altered mRNA expression. Plasma parameters were also measured.Results and conclusions: Perinatal exposure to EPOX induces transgenerational effects with phenotypic, histological and transcriptomic changes in the liver. These changes are highly dependent on the sex and generation of the animal. All these modifications lead to an alteration of the hepatic metabolism resulting in a difference in the size of the hepatocytes. Beyond these specific mechanisms, EPOX also seems to have a more general impact on hepatic metabolism via the circadian rhythm.