Prenatal amoxicillin exposure induces developmental toxicity in fetal mice and its characteristics

Amoxicillin, a widely used antibiotic in human and veterinary pharmaceuticals, is now considered as an "emerging contaminant" because it exists widespreadly in the environment and brings a series of adverse outcomes. Currently, systematic studies about the developmental toxicity of amoxicillin are still lacking. We explored the potential effects of amoxicillin exposure on pregnancy outcomes, maternal/fetal serum phenotypes, and fetal multiple organ development in mice, at different doses (75, 150, 300 mg/(kg·day)) during late-pregnancy, or at a dose of 300 mg/(kg·day) during different stages (mid-/late-pregnancy) and courses (single-/multi-course). Results showed that prenatal amoxicillin exposure (PAmE) had no significant influence on the body weights of dams, but it could inhibit the physical development and reduce the survival rate of fetuses, especially during the mid-pregnancy. Meanwhile, PAmE altered multiple maternal/fetal serum phenotypes, especially in fetuses. Fetal multi-organ function results showed that PAmE inhibited testicular/adrenal steroid synthesis, long bone/cartilage and hippocampal development, and enhanced ovarian steroid synthesis and hepatic glycogenesis/lipogenesis, and the order of severity might be gonad (testis, ovary) > liver > others. Further analysis found that PAmE-induced multi-organ developmental and functional alterations had differences in stages, courses and fetal gender, and the most obvious changes might be in high-dose, late-pregnancy and multi-course, but there was no typical rule of a dose-response relationship. In conclusion, this study confirmed that PAmE could cause abnormal development and multi-organ function alterations, which deepens our understanding of the risk of PAmE and provides an experimental basis for further exploration of the long-term harm.