The Maternal Blood Transcriptome Reflects Changes in Fetal Growth and Is an Accurate Predictor of Birth Weight in Cattle

Abstract

Harnessing information from maternal blood to predict fetal growth is an emerging area of research in livestock production, offering a noninvasive tool to monitor development. This study aimed to investigate temporal changes in blood gene expression during cow gestation through a bioinformatic approach and to determine the association between transcriptomic modifications in maternal blood at day 63 of gestation and calf birth weight (BW). Publicly available gene datasets from gestational days 0, 21, 42, 56, 63, and 105 were integrated to investigate maternal gene expression changes across gestation. Coexpression clustering identified four clusters, with three enriched for relevant biological processes, including interferon response genes from day 0 to 21, oxidative phosphorylation at day 42, and immune response genes by day 105. Additionally, maternal blood samples from 20 recipient cows carrying female fetuses derived from in vitro-produced embryos were subjected to RNA sequencing. Unsupervised weighted gene co-expression network analysis of these data identified four modules of coexpressed genes correlated with calf BW (p < 0.05). Supervised analysis revealed 189 differentially expressed genes (DEG; FDR < 0.05) associated with calf BW. The 106 positively associated DEG enriched phosphorylation and protein modification, while the 83 negatively associated DEG enriched immune processes. Biomarker genes were best determined using genes affected by gestational age and DEG, yielding 26 and 17 biomarkers, respectively, with R2 values of 0.88 and 0.75 for predicting calf BW. In conclusion, transcriptomic analysis of the maternal blood identified biomarkers associated with calf BW and may have application in other species.