Effects of amoxicillin exposure at different stages, doses and courses of pregnancy on adrenal development in fetal mice

Pregnant women are usually treated with amoxicillin before cesarean section to prevent infection. This study aimed to investigate the effects of amoxicillin exposure on fetal adrenal development at different stages, doses and courses of pregnancy. We found prenatal amoxicillin exposure (PAmE) could cause adrenal developmental toxicity in both male and female fetal mice in a stage, dose and course-dependent manner, among which the third trimester, high dose and multiple courses of PAmE could significantly reduce the maximum cross-sectional area and diameter. Besides, the proliferation was inhibited, the apoptosis was enhanced, and the serum corticosterone level and expression of steroidogenic enzymes were decreased in the PAmE group. Further, the insulin-like growth factor 1 (IGF1) signaling pathway were inhibited in the male and female fetal mice at the third trimester, high dose and multiple courses of treatment, and adrenal IGF1 expression was positively correlated with the indicators of adrenal development. In conclusion, PAmE could induce adrenal dysplasia in fetal mice in the stage, dose and course-dependent manner, which was related to the inhibition of IGF1 signaling pathway. This study provides guidance for evaluating the toxicity and risk of fetal adrenal development and the rational use of amoxicillin during pregnancy.