ABSTRACT: Background: This study investigated the effects of dietary soy isoflavone supplementation on reproductive performance, antioxidant capacity, and colostrum-derived exosomal microRNA profiles in sows, with the aim of exploring the molecular basis of maternal–offspring integrated regulation. A total of 120 Landrace × Yorkshire sows were assigned to either a control diet or a diet supplemented with 200 mg/kg soy isoflavone from gestation day 106 to lactation day 28. Reproductive performance and serum antioxidant indices were evaluated, and colostrum-derived exosomes were isolated for small RNA sequencing and bioinformatic analysis. Results: Dietary soy isoflavone supplementation significantly increased the total number of piglets born, the number of live-born piglets, litter weight at birth, and litter weight at weaning, while shortening farrowing duration (P < 0.05). In addition, soy isoflavone significantly elevated serum total antioxidant capacity and catalase activity on lactation day 21 (P < 0.05). Transmission electron microscopy, nanoparticle tracking analysis, and flow cytometry confirmed the successful isolation of colostrum-derived exosomes. Small RNA sequencing showed that most microRNAs ranged from 18 to 26 nucleotides, with a predominant peak at 22–23 nucleotides. Principal component analysis and differential expression analysis revealed that soy isoflavone markedly reshaped the microRNA cargo of colostrum-derived exosomes. Functional enrichment analysis indicated that the predicted target genes of differentially expressed microRNAs were mainly involved in transcriptional regulation, kinase-mediated signaling, inflammatory responses, and metabolic pathways, including mitogen-activated protein kinase, Ras, Rap1, endocytosis, autophagy, and adherens junction pathways. Integrated network analyses further suggested coordinated regulation of inflammatory signaling and metabolic homeostasis. Conclusions: Dietary soy isoflavone supplementation improved sow reproductive performance and antioxidant capacity, while reshaping colostrum-derived exosomal microRNA profiles and their associated regulatory networks. These findings provide a potential molecular basis for maternal–offspring integrated regulation.
