(P07-007-24) Tissue-Specific Impact of One-Carbon Metabolite Supplementation and Nutrient Restriction in Gestating Heifers on Fetal Mitochondrial-Related Gene Profiles

Objectives: The study investigated the effects of nutrient restriction and one-carbon metabolite (OCM) supplementation on mitochondrial-related gene expression in fetal liver and muscle of pregnant heifers on day 161 of gestation.

Methods: Twenty-nine crossbred Angus heifers, artificially inseminated, were assigned to one of four nutritional treatments using a 2 × 2 factorial design. The first factor, gain, compared a control diet (CON; 0.45 kg/day ADG) against a restricted diet (RES; -0.23 kg/day). The second factor, OCM supplementation, included either a supplemented group (+OCM; methionine [7.4 g/day] and ruminal protected choline [44.4 g/day] in a ground corn carrier, and injections of 20 mg vitamin B₁₂ and 320 mg folate weekly) or a non-supplemented group (-OCM; receiving saline injections and corn carrier). Fetal liver and muscle tissues were collected at 161 days of gestation for RNA extraction and transcriptomic analysis of mitochondrial-related differentially expressed genes (mtDEGs), followed by Gene Ontology (GO) and KEGG pathway analysis.

Results: Muscle tissues had more mtDEGs (90%) compared to hepatic tissues (10%), with the majority of muscle mtDEGs being downregulated (FDR P ≤ 0.1) in the RES and +OCM treatments. In both tissue types, RPL12—a gene crucial for protein metabolism and translation initiation increased in expression, peaking with a 2,485-fold rise within fetal liver from the CON+OCM. Notably, about one-third of mtDEGs, including ACSM1, FABP4, and PCK were similar across all treatments in muscle. Key GO processes such as the tricarboxylic acid cycle and gluconeogenesis were downregulated in muscle due to the main effects of gain and OCM (FDR P ≤ 0.05). KEGG pathway analysis revealed significant enrichment in pathways including the citrate cycle, pyruvate metabolism and PPAR signaling, indicating altered energy metabolism and stress response in muscle.

Conclusions: Nutrient restriction and OCM supplementation selectively affect mitochondrial-related processes in fetal muscle with minimal effects on liver, emphasizing tissue-specific responses and highlighting the intricate balance between fetal energy needs and metabolic adaptations during early development.

Funding Sources: Supported by the USDA, which is an equal-opportunity employer.