Prenatal iron overload induces hepatic oxidative stress and ferroptosis in offspring mice.

Abstract

Iron is an essential micronutrient required for normal growth and development. However, excessive iron intake can exert toxic effects, particularly during sensitive developmental windows such as pregnancy. In this study, pregnant female mice were supplemented with varying concentrations of iron until day 21 post-delivery. On postnatal days 0 and 21, we assessed the body weight, liver index, hepatic iron content, antioxidant capacity, and expression of ferroptosis-related proteins in the offspring. Excessive maternal iron supplementation significantly decreased both body and liver weights of offspring and induced histopathological abnormalities in hepatic tissue. Liver iron levels were markedly elevated, accompanied by significant reductions in the activities of antioxidant enzymes including T-AOC, CAT, GSH-Px, and SOD, as well as decreased hepatic GSH content. Moreover, iron overload increased the protein expression levels of p-AMPKα/AMPKα, p-ULK1/ULK1, Beclin1, FTH1, and COX2, while decreasing the levels of SLC7A11, GPX4, and NCOA4. Collectively, these findings suggest that excessive iron supplementation during pregnancy leads to hepatic iron accumulation, oxidative stress, and ferroptosis in offspring mice.