Supplementation of Melatonin During the Second Trimester Improves Liver Fibrosis in Piglets with Intrauterine Growth Restriction by Regulating Antioxidant Capacity

Intrauterine growth restriction (IUGR) frequently leads to abnormal fetal liver development and an elevated risk of long-term hepatic metabolic disorders. In this study, primiparous Landrace × Large White sows were used as a model to investigate the protective effects of melatonin supplementation during mid-gestation (days 60–90) on the liver of IUGR fetal pigs. The results showed that melatonin reduced the incidence of IUGR, improved fetal body weight and liver index, and alleviated hepatic structural disorganization, collagen deposition, and hepatic stellate cell activation. Meanwhile, melatonin decreased malondialdehyde levels, restored superoxide dismutase activity and total antioxidant capacity, and effectively mitigated oxidative stress. Transcriptomic validation revealed that melatonin partially counteracted IUGR-induced upregulation of extracellular matrix genes (e.g., COL1A2, COL3A1) and downregulation of antioxidant genes (e.g., GSTA1, GPX3), thereby shifting hepatic transcriptional profiles toward those observed in normal fetuses. In vitro experiments further confirmed that melatonin inhibited LX-2 cell activation and collagen overexpression. In conclusion, gestational melatonin supplementation can attenuate IUGR-associated fibrogenic alterations in IUGR fetal pigs by alleviating oxidative stress and remodeling the transcriptome, providing a novel basis for prenatal intervention.