PSVI-12 Effects of betaine supplementation and nutrient restriction during gestation on fetal metabolism in sheep.

Abstract Maternal nutrient restriction during gestation can significantly disrupt fetal programming, affecting the metabolism of the dam and causing adverse outcomes for fetal development. Supplementation of betaine, a methyl donor vital for growth and metabolism, has been demonstrated to improve insulin sensitivity and lipid metabolism, thereby enhancing metabolic responses in sheep. We hypothesized that maternal nutrient restriction during gestation would impair both dam and fetal metabolism, while betaine supplementation would improve metabolite concentrations. To evaluate the effects of maternal betaine supplementation during gestation on fetal circulating glucose and insulin levels in the offspring of restricted-fed dams, as well as maternal circulating glucose, insulin, and leptin concentrations, 32 multiparous Dorset ewes were estrus-synchronized and bred to one of three rams. Ewes confirmed pregnant with twins were randomly assigned to one of four diets [100% NRC requirements (CON), 60% NRC (RES), CON+betaine (CON+BET; 2 g/day), and RES+BET] from day 30 to 130 of gestation. The offspring included 27 males (CON:8, RES:5, CON+BET:5, and RES+BET:9) and 37 females (CON:8, RES:9, CON+BET:11, and RES+BET:9). Blood samples were collected from the dams on days 30 and 130 of gestation, while fetal blood samples were obtained during necropsy on day 130. The study utilized one-way ANOVA to assess the impact of four diets (CON, RES, CON+BET, RES+BET) on dam metabolite concentrations and two-way ANOVA to evaluate the effects of these diets on twin fetuses, with fetal sex as a covariate. Data were analyzed using RStudio with P ≤ 0.05 considered significant and 0.05 < P ≤ 0.10 as tendency. Glucose, insulin, and leptin concentrations in dams were not significantly different between diet groups at gestation days 30 and 130 (P ≥ 0.57). Maternal diet affected fetal glucose and insulin concentrations, while an effect of fetal sex was not detected. Fetal glucose concentrations were less in the RES (5.93 ± 1.7 mg/dL) and RES+BET (6.7 ± 1.48 mg/dL) compared with the CON (11.70 ± 1.58 mg/dL; P ≤ 0.03), while BET+CON showed no significant difference from other dietary groups (8.75 ± 1.78 mg/dL; P ≥ 0.22). Fetal insulin concentrations were reduced in the RES (0.030 ± 0.007 ng/mL) and RES+BET (0.034 ± 0.006 ng/mL) compared with the CON (0.056 ± 0.006 ng/mL; P ≤ 0.03), while the BET+CON (0.038 ± 0.007 ng/mL; P ≥ 0.16) were not different from all other diets. These findings suggest the significance of maternal nutrition and the need for further studies to assess betaine’s potential as a metabolic intervention in nutrient-restricted conditions.