Texas A&M AgriLife Research and Extension Center, Amarillo, TX 79106, USA.
Department of Animal Science, Texas A&M University, Amarillo, TX 79106, USA.
J Anim Sci. 2024 Jan 3;102. doi: 10.1093/jas/skae305.
The mechanistic target of rapamycin (mTOR) predominantly regulates the expression and activity of placental nutrient transporters. The mTOR pathway can be activated by several nutrients, including the essential amino acid methionine. Additionally, previous research in nonruminant animals suggests that mTOR is influenced in a sexually dimorphic manner. In bovine, there is limited understanding of how maternal nutrition and offspring sexual dimorphism affect the placental transfer of nutrients. Thus, we investigated the effects of increasing the supply of dietary methionine to beef cattle heifers during mid-gestation on mTOR signaling, placental nutrient transporters, and fetal growth in male and female offspring. Forty purebred Angus heifers were used in a randomized complete block design experiment. From days 90 to 180 of gestation, heifers received a basal diet with no added methionine (CON, n = 20), or the basal diet plus 8.3 g of rumen-protected methionine (MET, n = 20) per animal daily. All animals received a basal diet in the first and third trimesters of gestation. Cotyledonary tissue samples were collected at parturition and utilized to examine the mTOR pathway and nutrient transporters through protein and gene expression analysis. The offspring's body weight was measured at birth. Data were analyzed using a mixed model that included the fixed effect of treatment, offspring sex, their interactions, and the random effect of block. At day 170 of gestation, MET-supplemented heifers showed higher plasma concentrations of methionine and glutamate (P < 0.01) and lower glycine and proline levels (P ≤ 0.01) compared to the CON group. A treatment × sex interaction was observed for calf birth weight (P = 0.03). In heifers that delivered male calves, MET supplementation increased the birth weight of the calves (P < 0.01). However, the dietary treatments had no effect on the birth weight of female calves (P = 0.32). The increase in birth weight of male calves from MET-fed heifers resembles the upregulation of placental mTOR and phosphorylated mTOR (P ≤ 0.03), as well as the amino acid transporters SLC1A5, SLC7A5, SLC38A6, and SLC38A11, and the glucose transporters SLC2A1 and SLC2A8 (P ≤ 0.05). Our findings suggest that increasing the supply of methionine to beef heifers during mid-gestation can modulate placental nutrient transport and fetal growth in a sex-dependent manner and that these effects are mediated, at least in part, by the mTOR pathway.
机械靶向雷帕霉素（mTOR）主要调节胎盘营养转运体的表达和活性。mTOR 途径可被多种营养物质激活，包括必需氨基酸蛋氨酸。此外，非反刍动物的先前研究表明，mTOR 以性二态的方式受到影响。在牛中，对于母体营养和后代性别二态性如何影响营养物质在胎盘的转运，我们知之甚少。因此，我们研究了在妊娠中期增加日粮中蛋氨酸供应量对雄性和雌性后代中牛胎儿 mTOR 信号、胎盘营养转运体和胎儿生长的影响。40 头纯种安格斯小母牛采用随机完全区组设计试验。从妊娠 90 天到 180 天，小母牛接受基础日粮，不添加蛋氨酸（CON，n=20），或基础日粮加 8.3g 瘤胃保护性蛋氨酸（MET，n=20）/头/天。所有动物在妊娠的第一和第三 trimester 都接受基础日粮。分娩时采集胎盘中的组织样本，通过蛋白质和基因表达分析检测 mTOR 途径和营养转运体。在出生时测量后代的体重。使用包含处理、后代性别、它们的相互作用以及区组的随机效应的混合模型分析数据。在妊娠 170 天，与 CON 组相比，补充 MET 的小母牛的血浆蛋氨酸和谷氨酸浓度更高（P<0.01），甘氨酸和脯氨酸水平更低（P≤0.01）。观察到小牛出生体重存在处理×性别相互作用（P=0.03）。在产雄性小牛的小母牛中，MET 补充增加了小牛的出生体重（P<0.01）。然而，日粮处理对雌性小牛的出生体重没有影响（P=0.32）。来自 MET 喂养小母牛的雄性小牛出生体重的增加类似于胎盘 mTOR 和磷酸化 mTOR 的上调（P≤0.03），以及氨基酸转运体 SLC1A5、SLC7A5、SLC38A6 和 SLC38A11，以及葡萄糖转运体 SLC2A1 和 SLC2A8（P≤0.05）。我们的研究结果表明，在妊娠中期增加蛋氨酸的供应可以以性别依赖的方式调节胎盘营养物质的转运和胎儿的生长，并且这些影响至少部分是通过 mTOR 途径介导的。
