Methionine and guanidinoacetic acid supplementation throughout the periconceptual period of gestation altered metabolite concentrations and fetal development in beef heifers

Authors: HAUXWELL, KATHLYN - North Dakota State University; Cushman, Robert; CATON, JOEL - North Dakota State University; WARD, ALISON - North Dakota State University; Lindholm-Perry, Amanda; Snider, Alexandria; FREETLY, HARVEY - Retired ARS Employee; DAHLEN, CARL - North Dakota State University; AMAT, SAMAT - North Dakota State University; SWANSON, REBECCA - South Dakota State University; Stromer, Bobbi; Neville, Bryan; THORSON, JENNIFER - Former ARS Employee; Oliver, William; Miles, Jeremy; Crouse, Matthew

Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/17/2026
Publication Date: 3/9/2026
Citation: Hauxwell, K.M., Cushman, R.A., Caton, J.S., Ward, A.K., Lindholm-Perry, A.K., Snider, A.P., Freetly, H.C., Dahlen, C.R., Amat, S., Swanson, R.M., Stromer, B.S., Neville, B.W., Thorson, J.F., Oliver, W.T., Miles, J.R., Crouse, M.S. 2026. Methionine and guanidinoacetic acid supplementation throughout the periconceptual period of gestation altered metabolite concentrations and fetal development in beef heifers. Journal of Animal Science. 104. Article skag067. https://doi.org/10.1093/jas/skag067.
DOI: https://doi.org/10.1093/jas/skag067

Interpretive Summary: Methionine is an essential amino acid that supports gene activity and tissue growth in both humans and livestock. Guanidinoacetic acid is a nonessential amino acid used to make creatine, which fuels energy storage and muscle development, and in doing so it uses some of the same molecules that methionine creates for DNA regulation. This study investigated the roles of these two amino acids on fetal development and was conducted with four treatments: no amino acid supplement, supplemental rumen-protected methionine, supplemental rumen-unprotected guanidinoacetic acid, and combination supplementation of rumen-protected methionine and rumen-unprotected guanidinoacetic acid for 63 days before breeding until day 63 of gestation when fetal tissues were collected. Supplementing rumen-protected methionine to beef heifers during the breeding season through early gestation resulted in increased fetal tissue growth through increased brain weight, rumen and intestine weight, and skeletal muscle weight; however, supplementation of unprotected guanidinoacetic acid failed to result in changes to guanidinoacetic acid or its downstream metabolite creatine in the dam, and had minimal effects on growth metrices in the fetus, only decreasing fetal testes weight. These data indicate potential positive benefit of methionine supplementation to early fetal development but calf data would be needed to determine any long-term benefits.

Technical Abstract: Recent research reported changes in fetal growth due to increased methyl donor availability through periconceptual supplementation of the dam. We hypothesized that maternal supplementation of methionine or guanidinoacetic acid during the periconceptual period will result in a methyl donor surplus or deficiency in dams, respectively, and ultimately influence fetal development on d 63 of gestation. The objectives of this study were to evaluate the effects of methyl donor surplus or deficiency during the periconceptual period of gestation on metabolite concentrations in the dam, and on early fetal development. Eighty beef heifers (n = 20/treatment, age = 384 ± 10 d, initial BW = 346 ± 8 kg) were stratified by age and weight to one of four treatment groups to receive 100 g total of supplement: ground corn carrier (100 g/d) as control (CON), methionine (10 g/d) in ground corn (90 g/d; MET), guanidinoacetic acid (40 g/d) in ground corn (60 g/d; GAA), and MET+GAA (10 g/d MET + 40 g/d GAA) in ground corn (50 g/d). Supplementation began 63 d before breeding (d -63), through breeding (d 0), and lasted until d 63 of gestation (d +63). Serum samples were collected from the heifers before feeding on d -63, d 0, and d +63. Heifers were bred using male sexed semen from a single sire, and 35 heifers were confirmed pregnant (CON, n = 10; MET, n = 8; GAA, n = 7; MET+GAA, n = 10) and harvested on d +63 of gestation to collect maternal and fetal samples. Data were analyzed as a 2 × 2 factorial arrangement with 2 levels of methionine and 2 levels of guanindinoacetic acid. Methionine concentrations in maternal serum were greater (P = 0.05) in MET and MET+GAA compared with CON and GAA supplemented heifers at breeding on d 0 and d +63. No differences (P >/= 0.15) in the concentration of guanidinoacetic acid or creatine were observed between treatment groups; however, both were decreased at breeding (P < 0.01) compared with d -63 and d +63. Averaged across timepoints, S-adenosyl methionine (SAM) (P = 0.05) and homocysteine (P = 0.01) concentrations in maternal serum were decreased in MET and MET+GAA compared with CON and GAA. Fetuses from methionine supplemented dams had greater (P = 0.01) brain and longissimus dorsi weights compared with those not receiving methionine. Methionine supplementation increased maternal serum methionine concentrations and increased early fetal tissue development, suggesting altered methionine utilization in utero.