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

Abstract 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 hydroxy-Met analogue (OHMet) improve placental function, forty sows were divided into four groups and fed with either a control diet (CON), 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 (TMT) based quantitative proteomic analysis. Results Here, we reported that 0.15%OHMet consumption significantly increased the placental vascular density compared with the CON group. Proteomic analysis identified 5136 proteins; of these, 87 differentially expressed proteins were screened (P < 0.05, |fold change| > 1.2). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriched in 0.15%OHMet vs. CON and in 0.15%OHMet vs. 0.3%OHMet were glutathione metabolism, and in 0.15%OHMet vs. 0.3%Met were NOD-like receptor signaling pathway 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 CON and 0.3%OHMet groups, upregulated the protein expression of 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 CON group, 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 methionine, was shown to damaged placental function by inhibiting the protein expression of TXN, and leading to apoptosis and ROS production. Conclusion In contrast to improved placental angiogenesis and increased antioxidative capacity by dietary 0.15%OHMet supplementation, 0.3%OHMet or 0.3%Met supplementation impaired placental function via aggravating inflammation and oxidative stress, which is associated to cumulative homocysteine levels.