Abstract
BACKGROUNDS: Heavy metals affect various processes in the embryonic development. Embryonic fibroblasts (EFs) play key roles in the innate recognition and wound healing in reproductive tissues. METHODS: Based on the relative toxicities of different inorganic metals and inorganic nonmetallic compounds against murine and chicken EF cells, mechanistic estimations were performed based on transcriptomic analyses. RESULTS: Lead (II) acetate induced preferential injuries in the chicken EF and mechanistic analyses using transcriptome revealed that chemokine receptor-associated events are potently involved in metal-induced adverse actions. As an early sentinel of metal exposure, the precision-cut intestine slices (PCIS) induced the expression of chemokines including CXCLi1 or CXCLi2, which were potent gut-derived factors that activate chemokine receptors in reproductive organs after circulation. CONCLUSION: EF-selective metals can be estimated to trigger the chemokine circuit in the gut-reproductive axis of chickens. This in vitro methodology using PCIS-EF culture could be used as a promising alternate platform for the reproductive immunotoxicological assessment.