Nutrient transporter expression in bovine utero‐placental tissue is altered by the supply of dietary methionine during late‐gestation

Abstract

The placenta performs an indispensable function delivering essential nutrients for fetal growth. In humans, evidence indicates that mammalian target of rapamycin (mTOR) acts as a placental nutrient sensor that could alter the activity of placental amino acid (AA) transporters. We hypothesized that increasing methionine supply during late pregnancy improves placental nutrient transport in dairy cows through the mTOR pathway. To test our hypothesis, sixty‐one multiparous cows were fed the experimental treatments consisting of a basal control [CON; n=31; 1.47 Mcal/kg dry matter (DM) and 15.3% crude protein (CP)] diet with no added methionine or the basal diet plus rumen‐protected methionine (MET; Mepron®, Evonik Nutrition & Care GmbH, Germany; n=30). Placentome samples were collected from 15 cows per treatment based on body condition score of the cows at −30 days before parturition (3.64 ± 0.3; scale 1 to 5), number of days that the cows received the treatments (27 ± 1.8), calf sex (eight females and seven males per treatment) and calf birthweight (94 kg ± 10). Methionine was supplied from −28 days to parturition at a rate of 0.09% of diet DM. From −45 to −29 days before expected parturition, all cows received the same diet (1.33 Mcal/kg DM and 13.9% CP) with no MET. mTOR and RPS6KB1 (ribosomal protein S6 kinase beta‐1) had greater (P ≤ 0.07) mRNA expression in cows that received MET compared with CON, whereas AKT1, EIF4EBP1, EIF4EBP2, EEF1A1, ELF2 and IRS expression was not altered (P > 0.10). Cows supplemented with MET had greater (P ≤ 0.10) mRNA expression of heavy chain AA transporter (SLC3A2), branched‐chain and aromatic AA (SLC7A5), neutral AA transporter (SLC38A1, SLC38A2), sodium‐dependent AA transporter (SLC38A10), and System L transporter (SLC43A2). In contrast, expression of the betaine transporter (SLC6A12) was lower (P = 0.06) in cows fed MET. The genes SLC1A1, SLC1A5, SLC6A6, SLC7A8, SLC38A6 and SLC38A7 that encode amino acid transporters were not affected (P > 0.10) by methionine supply. Among glucose transporters analyzed, both facilitated transporters SLC2A1 and SLC2A3 had greater (P = 0.06) mRNA expression in MET cows, while SLC2A8 was lower (P = 0.07). The other glucose transporters (SLC2A5, SLC2A6, SLC2A9, SLC2A10, SLC2A11, SLC2A12, SLC2A13 and SLC5A11) analyzed were not affected (P > 0.10) by methionine supply. Regarding the fatty acid transporters, MET cows had lower (P = 0.06) expression of SLC27A1, while SLC27A2 and SLC27A3 were not affected (P > 0.10). The sodium/multivitamin and iodine cotransporter (SLC5A6) had greater expression (P = 0.09) in MET cows. The vitamin transporters SLC19A2, SLC19A3, SLC44A1 and SLC44A3 were not affected (P > 0.10) by methionine supply. Overall, our results indicate that increasing methionine supply during late gestation increases utero‐placental transport of nutrients and it is mediated, at least in part, by the mTOR pathway.