143 Late-Breaking: Maternal vitamin and mineral supplementation modulate placental gene expression related to angiogenesis, nutrient transport, and immune regulation in neonatal beef heifers.

Abstract The placenta plays a central role in fetal development by regulating nutrient transfer, hormone signaling, and cellular differentiation, ultimately influencing long-term offspring productivity. This study examined the effects of maternal vitamin and mineral (VTM) supplementation on the gene expression profile of bovine placental tissue, focusing on hormone signaling, nutrient transport, and angiogenesis. Fourteen crossbred Angus heifers were estrus synchronized, bred to female-sexed semen, and randomly assigned to either a basal diet (Control, CON; n = 7) or the basal diet plus VTM supplementation (Treatment, VTM; n = 7) throughout gestation. After parturition, the largest placentome closest to the umbilical cord was collected immediately following expulsion, and cotyledon samples were processed for RNA isolation. Gene expression was analyzed using RNA-Seq, with differentially expressed genes identified via DESeq2. Maternal VTM supplementation did not significantly affect calf birth weight. However, 242 genes were differentially expressed; 156 genes were upregulated, and 86 were downregulated in placentas from VTM (P ≤ 0.05 and |log2FC| > 0.5). Functional enrichment analysis of DEGs using ClueGO revealed biological processes critical to placental function, including angiogenesis, extracellular matrix composition, epithelial proliferation, and immune regulation. Key genes such as F2R, SULF1, FGF2, CREB3L1, NOTCH2, and RUNX2 were over-represented in organ morphogenesis, vascular development, and cellular repair pathways. These findings support our observation of increased vascular area density in the placenta of VTM supplemented heifers. Previous research has suggested that F2R signaling was associated with enhanced angiogenesis, driven by increased expression of VEGF and matrix metalloproteinases, playing a role in vascular adaptations essential for fetal growth. Additionally, F2R contributes to immune regulation at the maternal-fetal interface by modulating inflammatory cytokine responses, ensuring proper immune tolerance during pregnancy. Further analysis revealed that HMOX1 and ITGA5 were upregulated in the VTM group, genes associated with oxidative stress regulation and cell adhesion, respectively. HMOX1 is known to support placental vascular integrity and modulate maternal immune responses, contributing to a stable intrauterine environment. Elevated HMOX1 expression has been associated with reduced oxidative damage in the placenta, which is key for sustaining fetal development and may reduce the risk of intrauterine growth restriction. ITGA5, a member of the integrin family, plays a role in the structural organization of the extracellular matrix, which is necessary for placental anchoring and stability. Increased expression of ITGA5 has been linked to improved trophoblast attachment and invasion, which influence placental efficiency and nutrient exchange capacity. These findings highlight the role of maternal VTM supplementation in optimizing placental function and fetal development through the regulation of key molecular pathways. Understanding the impact of maternal nutrition on placental gene expression provides valuable insight into mechanisms influencing pregnancy outcomes, with potential implications for improving livestock production efficiency and neonatal health.