The correlation between oxidative stress and liver metabolic dysfunction in piglets with intrauterine growth restriction (IUGR) remains limited. Therefore, the objective of the present study was to investigate potential mechanisms of metabolic characteristics induced by oxidative stress in the livers of IUGR piglets using metabolomic and transcriptomic analysis. Analysis of the phenotypic characteristics showed that the liver weight of the intrauterine growth restriction piglets was significantly lower than that of normal birth weight piglets. Intrauterine growth restriction piglets exhibited disordered hepatic cord arrangement and vacuolization as well as excessive lipid accumulation in hepatocytes. In addition, the activities of antioxidant enzymes were significantly decreased in the liver of the intrauterine growth restriction piglets, whereas the level of the lipid peroxidation marker MDA was significantly increased. Finally, our findings revealed that intrauterine growth restriction piglets were involved in a variety of metabolic abnormalities, including mitochondrial dysfunction, imbalance of fatty acid composition, disruption to sources of one-carbon unit supply, and abnormal galactose conversion, which may be responsible for oxidative stress in the liver. In summary, these data provided a detailed theoretical reference for revealing the hepatic metabolic characteristics of intrauterine growth restriction piglets.

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.

Vitamin D and its metabolite 25-hydroxyvitamin D₃ (25-OH-D₃) are central to calcium homeostasis, maternal skeletal integrity, and sow reproductive efficiency. This study compared vitamin D₃ with an equivalent supranutritional dose of chemically or microbially produced 25-OH-D₃ from day 90 of gestation to weaning. A total of 100 Large White × Landrace sows were assigned to five treatments (n = 20): a basal control (25 µg/kg vitamin D₃), a VD₃ group (basal + 50 µg/kg vitamin D₃), and three 25-OH-D₃ groups (basal + 50 µg/kg 25-OH-D₃; QV1–QV3). Reproductive traits, colostrum composition, serum vitamin D-related indices, antioxidant and cytokine profiles, pre-weaning piglet growth, femoral mineral concentration, intestinal morphology, and barrier-related gene expression were assessed. Compared with the control, QV2 increased litter weight gain from birth to day 14 by 9.8%, piglet serum 25-OH-D₃ at weaning by 33.2%, and femoral calcium concentration by 14.4% (p < 0.05); litter and average piglet weights at weaning were unchanged. Maternal 25-OH-D₃ supplementation also altered the overall redox profile and several circulating inflammatory cytokines, increased jejunal and ileal villus height in the QV2 and QV3 groups, and upregulated selected tight-junction-related genes, including occludin and ZO-1, in a source- and intestinal-segment-dependent manner (p < 0.05). Responses were source-dependent, and QV2 showed the strongest effects for selected endpoints; the data do not support class-wide superiority of biosynthesized preparations.

Intrauterine growth restriction (IUGR) has a negative impact on reproductive performance in domestic animals. In this study, we attempt to explore the etiology of IUGR in sows and test the potential beneficial effects and underlying molecular mechanisms of melatonin on IUGR. The results indicated that there was a negative correlation between the concentration of melatonin in the peripheral blood of pregnant sows and the ratio of IUGR, and the concentration of melatonin in the umbilical cord blood of IUGR piglets was abnormally decreased. Supplementing sows with an appropriate dose of melatonin can increase the average birth weight of piglets and reduce the proportion of IUGR piglets. Reduced representation bisulfite sequencing revealed a direct association between abnormal DNA methylation in the placenta of sows and IUGR piglets. The increased DNA methylations of key genes responsible for placenta functions downregulated their expressions. Gene downregulation caused placenta dysfunction and IUGR. Melatonin significantly reduced DNA methylation of genes related to placental function. We identified that melatonin supplementation during mid-gestation stages specifically targeted the CGI, CGI shore, exon, intron, and 3′ untranslated regions of placental genes. The results provide novel information to target the high incidence of IUGR in pigs as well as other species.