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 day 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 with 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.

中文翻译：

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妊娠中期的蛋氨酸供应以性别特异性方式调节牛胎盘 mTOR 通路、营养转运蛋白和后代出生体重


雷帕霉素的机制靶标 （mTOR） 主要调节胎盘营养转运蛋白的表达和活性。mTOR 通路可被多种营养素激活，包括必需氨基酸蛋氨酸。此外，先前对非反刍动物的研究表明，mTOR 以性二态方式受到影响。在牛中，对母体营养和后代性二态性如何影响胎盘营养物质的转移了解有限。因此，我们研究了在妊娠中期增加肉牛小母牛日粮蛋氨酸供应对雄性和雌性后代 mTOR 信号、胎盘营养转运蛋白和胎儿生长的影响。40 头纯种安格斯小母牛用于随机完整区组设计实验。从妊娠第 90 天到第 180 天，小母牛接受不添加蛋氨酸的基础日粮 （CON， n = 20），或基础日粮加 8.3 克瘤胃保护蛋氨酸 （MET， n = 20） 每头动物每天。所有动物在妊娠早期和晚期都接受基础饮食。在分娩时收集子叶组织样本，并通过蛋白质和基因表达分析检测 mTOR 通路和营养转运蛋白。后代的体重在出生时测量。使用混合模型分析数据，该模型包括治疗的固定效应、后代性别、它们的相互作用和块的随机效应。在妊娠第 170 天，与 CON 组相比，补充 MET 的小母牛血浆蛋氨酸和谷氨酸浓度较高 （P < 0.01） 和甘氨酸和脯氨酸水平较低 （P ≤ 0.01）。观察到×犊出生体重的性互动处理 （P = 0.03）。 在分娩雄性犊牛的小母牛中，补充 MET 增加了犊牛的出生体重 （P < 0.01）。然而，日粮处理对母牛犊的出生体重没有影响 （P = 0.32）。MET 喂养的小母牛雄性犊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），以及氨基酸转运蛋白 SLC1A5、SLC7A5、SLC38A6 和 SLC38A11，以及葡萄糖转运蛋白 SLC2A1 和 SLC2A8 （P ≤ 0.05）。我们的研究结果表明，在妊娠中期增加肉牛蛋氨酸的供应可以以性别依赖性方式调节胎盘营养物质运输和胎儿生长，并且这些影响至少部分是由 mTOR 途径介导的。