One-carbon metabolites supplementation and nutrient restriction alter the fetal liver metabolomic profile during early gestation in beef heifers

Authors: SAFAIN, KAZI - North Dakota State University; Crouse, Matthew; SYRING, JESSICA - North Dakota State University; ENTZIE, YSSI - North Dakota State University; KING, LAYLA - North Dakota State University; HIRCHERT, MARA - North Dakota State University; WARD, ALISON - University Of Saskatchewan; REYNOLDS, LARRY - North Dakota State University; BOROWICZ, PAWEL - North Dakota State University; DAHLEN, CARL - North Dakota State University; SWANSON, KENDALL - North Dakota State University; CATON, JOEL - North Dakota State University

Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/4/2024
Publication Date: 9/4/2024
Citation: Safain, K.S., Crouse, M.S., Syring, J.G., Entzie, Y.L., King, L.E., Hirchert, M.R., Ward, A.K., Reynolds, L.P., Borowicz, P.P., Dahlen, C.R., Swanson, K.C., Caton, J.S. 2024. One-carbon metabolites supplementation and nutrient restriction alter the fetal liver metabolomic profile during early gestation in beef heifers. Journal of Animal Science. 102. Article skae258. https://doi.org/10.1093/jas/skae258.
DOI: https://doi.org/10.1093/jas/skae258

Interpretive Summary: Maternal stresses that occur during pregnancy, such as restricted nutrition, can impact the developmental outcomes of the offspring in a process known as developmental programming. This programming can occur through epigenetics, which involves changes in fetal gene expression and can occur through the addition of methyl groups to DNA or histone tails. These changes regulate gene transcription in the offspring. One-carbon metabolites (OCM) act as intermediates or cofactors for the donation of methyl groups to DNA and histones. This study investigated the effects of differing maternal rate of gain along with OCM supplementation during early gestation on OCM and related metabolite concentrations in the dam and fetus. We found that supplementing OCM to beef heifers increased maternal OCM and related metabolite concentrations and fetal fluid OCM concentrations. We also found that low maternal gain increased maternal serum and liver OCM concentrations. We can conclude from these findings that both maternal nutrition and OCM supplementation can impact maternal OCM concentrations at day 63 of gestation, and that although differences in fetal metabolites were minimal, further research is needed to see if those maternal impacts will affect the developing fetus or calf later in its life.

Technical Abstract: Maternal nutrition is pivotal for proper fetal development, with one-carbon metabolites (OCM) playing a key role in fetal epigenetic programming through DNA and histone methylation. The study aimed to investigate the effects of nutrient restriction and OCM supplementation on fetal liver metabolomics in pregnant beef-heifers, focusing on metabolites and pathways associated with amino-acid, vitamin and cofactor, carbohydrate, and energy metabolism at day 63 of gestation. Thirty-one crossbred Angus heifers were artificially inseminated and allocated to four nutritional treatments in a 2 × 2 factorial arrangement of treatments, with the two factors being dietary intake/rate of gain (control-diet [CON]; 0.60 kg/day ADG, vs. restricted-diet [RES]; -0.23 kg/day ADG) and OCM supplementation (supplemented [+OCM] vs. not supplemented [-OCM]). The resulting treatment groups—CON-OCM, CON+OCM, RES-OCM, and RES+OCM were maintained for 63 days post-breeding. Following this period, fetal liver tissues were collected and subjected to metabolomic analysis using UPLC-tandem mass-spectrometry. We identified 288 metabolites, with the majority (n = 54) being significantly influenced by the main effect of gain (P