Translating Maternal Vitamin and Mineral Supplementation Effect on Early Developing Fetus Through Hepatic Long Non-Coding Rnas Profile in Beef Heifers

Abstract Maternal nutrition is critical during pregnancy as the fetus relies on the nutrients from the dam. Fetal organogenesis starts during the first trimester. Thus, an appropriate supply of nutrients, including vitamins and minerals, is indispensable. In the field of fetal developmental programming, there is still a lack of knowledge based on appropriate livestock models to explain the role of regulatory factors in translating the effect of maternal minerals and vitamins on fetal development and metabolic function. Therefore, this study was designed to investigate the effect of maternal vitamin and mineral supplementation (VTM -d 71 periconceptual to d 83 of pregnancy) on fetal liver expression of long non-coding RNAs (lncRNAs) and their potential regulatory metabolic pathways. Angus crossbreed beef heifers (n = 16) were supplemented (VTM, n = 8) or not (NoVTM, n = 8) with 113 g· heifer-1· day-1 of mineral premix (Purina Wind & Rain Storm All-Season 7.5 Complete) and all heifers were bred with female sexed semen from a single sire. Transcriptomic profiles were determined with RNA-Seq in fetal livers collected on d 83 ± 0.27 of gestation. After data quality control and read mapping, lncRNAs were predicted using the FEELnc pipeline. Using the DESeq2 software, we identified 50 differentially expressed novel lncRNAs (expression of 32 lncRNAs was upregulated and 18 were downregulated; FDR < 0.05) located either downstream, upstream, or in exonic, or intronic regions of 51 genes (including PFKP, SLC30A10, KCNH8, ZNF451, MINPP1, BCL9, PAH, ITPR2, AHCY, and ABCG8), potentially regulating their expression. These genes could affect pathways (FDR < 0.1) such as PI3K signaling, mineral storage and transport, and amino acids biosynthetic pathways (i.e., cysteine and methionine biosynthesis). Collectively, these results suggest that periconceptual maternal vitamin and mineral supplementation affects the expression of lncRNAs and potentially regulates the expression of genes involved in fetal liver development and function.