Poor maternal nutrition can negatively affect fetal and placental growth and development. However, the mechanism(s) that contribute to altered placenta growth and function are not well understood. We hypothesized that poor maternal diet would impact signaling through the C-X-C motif chemokine ligand (CXCL) 12-CXCL4 axis and/or placental expression of the insulin-like growth factor (IGF) axis. Using our established sheep model of poor maternal nutrition, we examined the effects of restricted- and over-feeding on ewe placentome gene and protein expression. Specifically, ewes were fed a control (CON; 100%), restricted (RES; 60%), or over (OVER; 140%) diet beginning at day 30.2 ± 0.02 of gestation, and samples were collected at days 45, 90, and 135 of gestation, representing periods of active placentation, peak placental growth, and near term, respectively. Placentomes were separated into cotyledon and caruncle, and samples snap frozen. Protein was determined by western blot and mRNA expression by real-time PCR. Data were analyzed by ANOVA and significance determined at P ≤ 0.05. Ewes fed a RES diet had decreased CXCL12 and vascular endothelial growth factor (VEGF), and increased tumor necrosis factor (TNF)α protein compared with CON ewes in caruncle at day 45 (P ≤0.05). In day 45 cotyledon, CXCR7 protein was increased and mTOR was decreased in RES relative to CON (P ≤0.05). At day 90, CXCR4 and CXCR7 were reduced in RES caruncle compared with CON, whereas VEGF was reduced and mTOR increased in cotyledon of RES ewes relative to CON (P ≤0.05). In OVER caruncle, at day 45 CXCR4 and VEGF were reduced and at day 90 CXCR4, CXCR7, and TNFα were reduced in caruncle compared with CON (P ≤0.05). There was no observed effect of OVER diet on protein abundance in the cotyledon (P > 0.05). Expression of IGF-II mRNA was increased in OVER at day 45 and IGFBP-3 was reduced in RES at day 90 in caruncle relative to CON (P ≤0.05). Maternal diet did not alter placentome diameter or weight (P > 0.05). These findings suggest that restricted- and over-feeding negatively impact protein and mRNA expression of key chemokines and growth factors implicated in proper placenta development and function.

中文翻译：

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妊娠期母体营养限制和过度喂养会改变参与胎盘发育和血管形成的关键因子的表达

母亲营养不良会对胎儿和胎盘的生长发育产生负面影响。然而，导致胎盘生长和功能改变的机制尚不清楚。我们假设不良的母亲饮食会影响通过 CXC 基序趋化因子配体 (CXCL) 12-CXCL4 轴和/或胰岛素样生长因子 (IGF) 轴的胎盘表达的信号传导。使用我们建立的母体营养不良的绵羊模型，我们检查了限制和过度喂养对母羊胎盘基因和蛋白质表达的影响。具体来说，从妊娠第 30.2 ± 0.02 天开始，母羊被喂食对照（CON；100%）、限制（RES；60%）或过量（OVER；140%）饮食，并在第 45、90、90 天收集样本。和 135 妊娠，代表活跃的胎盘，胎盘生长高峰期和近期，分别。胎盘体被分成子叶和肉阜，样品快速冷冻。通过蛋白质印迹测定蛋白质，通过实时 PCR 测定 mRNA 表达。通过 ANOVA 分析数据，并在 P ≤ 0.05 时确定显着性。与 CON 母羊相比，在第 45 天，饲喂 RES 日粮的母羊 CXCL12 和血管内皮生长因子 (VEGF) 减少，肿瘤坏死因子 (TNF)α 蛋白增加 (P ≤ 0.05)。在第 45 天的子叶中，相对于 CON，RES 中 CXCR7 蛋白增加，mTOR 减少（P ≤ 0.05）。在第90天，与CON相比，RES母羊肉阜中CXCR4和CXCR7减少，而相对于CON，RES母羊子叶中VEGF减少而mTOR增加（P≤0.05）。在 OVER 肉阜中，与 CON 相比，第 45 天 CXCR4 和 VEGF 减少，第 90 天 CXCR4、CXCR7 和 TNFα 减少（P ≤ 0.05）。没有观察到过度饮食对子叶中蛋白质丰度的影响(P＞0.05)。相对于 CON，第 45 天 OVER 中 IGF-II mRNA 的表达增加，第 90 天 RES 中 IGFBP-3 减少（P ≤ 0.05）。母亲的饮食没有改变胎盘直径或重量（P > 0.05）。这些发现表明，限制和过度喂养会对与胎盘正常发育和功能有关的关键趋化因子和生长因子的蛋白质和 mRNA 表达产生负面影响。