Increased maternal consumption of methionine as its hydroxyl analog improves placental angiogenesis and antioxidative capacity in sows.

BACKGROUND: Previous evidence suggests that methionine (Met) consumption can promote placental angiogenesis and improve fetal survival. To investigate the mechanisms by which increased levels of Met as hydroxyl-Met (OHMet) improve placental function, forty sows were divided into four groups and fed either a control diet, or diets supplemented with 0.15% OHMet, 0.3% OHMet or 0.3% Met (n = 10). Placentas were collected immediately after expulsion, and extracted proteins were analyzed by tandem mass tag based quantitative proteomic analysis. RESULTS: We found that 0.15% OHMet consumption significantly increased placental vascular density compared with the control. Proteomic analysis identified 5,136 proteins, 87 of these were differentially expressed (P < 0.05, |fold change| > 1.2). Enriched pathways in the Kyoto Encyclopedia of Genes and Genomes for 0.15% OHMet vs. control and 0.15% OHMet vs. 0.3% OHMet were glutathione metabolism; for 0.15% OHMet vs. 0.3% Met, they were NOD-like receptor signaling and apoptosis. Further analysis revealed that 0.15% OHMet supplementation upregulated the protein expression of glutathione-S-transferase (GSTT1) in placentas and trophoblast cells compared with the control and 0.3% OHMet groups, upregulated thioredoxin (TXN) in placentas and trophoblast cells compared with the 0.3% OHMet and 0.3% Met groups, and decreased reactive oxygen species (ROS) levels in trophoblast cells compared with other groups. In contrast, sows fed 0.3% OHMet or 0.3% Met diets increased placental interleukin 1β levels compared with the control, and upregulated the protein expression of complex I-B9 (NDUFA3) compared with the 0.15% OHMet group. Furthermore, homocysteine, an intermediate in the trans-sulphuration pathway of Met, damaged placental function by inhibiting the protein expression of TXN, leading to apoptosis and ROS production. CONCLUSION: Although dietary 0.15% OHMet supplementation improved placental angiogenesis and increased antioxidative capacity, 0.3% OHMet or 0.3% Met supplementation impaired placental function by aggravating inflammation and oxidative stress, which is associated with cumulative homocysteine levels.