Genetic regulation and variation of fetal plasma metabolome in the context of sex, paternal breeds and variable fetal weight

Metabolic processes in fetuses can significantly influence piglet weight at birth. Understanding the genetic determinants of systemic metabolism is crucial for uncovering how genetic and molecular pathways impact biological mechanisms, particularly during the fetal phase. We present data on 1112 plasma metabolites using untargeted ultra-high performance liquid chromatography-tandem mass spectrometry methods, of 260 backcross (BC) fetuses from two sires' breeds at 63 days post-conception. Eight chemical superclasses have been identified, with lipids accounting for the majority of metabolites. Genomic heritability (h²) was estimated for each metabolite, revealing that 50% had h² values below 0.2, with a higher average in the amino acid class compared with the lipid. We annotated 448 significant metabolite quantitative trait loci associated with 10 metabolites, primarily lipids, indicating strong genetic regulation. Additionally, metabolite associations with sex, fetal weight and sire's breed were explored, revealing significant associations for 354 metabolites. Fetal weight influenced the largest number of metabolites, particularly glycerophospholipids and sphingolipids, emphasizing the genetic and metabolic complexity underlying fetal development. These findings enhance our understanding of the genetic regulation of metabolite levels and their associations with key phenotypic traits in fetuses, providing insights into metabolic pathways, potential biomarkers and serving as a baseline dataset for metabolomics studies of fetuses.