Neville T L, Redmer D A, Borowicz P P, Reed J J, Ward M A, Johnson M L, Taylor J B, Soto-Navarro S A, Vonnahme K A, Reynolds L P, Caton J S
Center for Nutrition and Pregnancy, Department of Animal Sciences, North Dakota State University, Fargo, North Dakota 58108, USA.
J Anim Sci. 2010 Aug;88(8):2692-702. doi: 10.2527/jas.2009-2706. Epub 2010 Apr 20.
The objectives of this study were to evaluate effects of maternal dietary restriction and Se supply on angiogenic factor mRNA expression in intestinal and mammary tissues, and jejunal crypt cell proliferation and vascularity in late-term fetal intestines. In Exp. 1, pregnant ewe lambs (n = 32; initial BW = 45.6 +/- 2.3 kg) were allotted randomly to 1 of 4 treatments. Treatments (initiated d 50 +/- 5 of gestation) were control (3.5 microg of Se.kg of BW(-1).d(-1)), Se-wheat (75 microg of Se.kg of BW(-1).d(-1)), selenate (Se3; providing 75 microg of Se.kg of BW(-1).d(-1)), selenate (Se15; providing 375 microg of Se.kg of BW(-1).d(-1)). Diets (DM basis) were similar in CP (15.5%) and ME (2.68 Mcal/kg). In Exp. 2, pregnant ewe lambs (n = 36; initial BW 53.8 +/- 1.3 kg) were allotted randomly to treatments in a 2 x 2 factorial arrangement. Factors were nutrition (control, 100% of requirements vs. restricted nutrition, 60% of controls) and dietary Se (adequate Se; 6 microg of Se.kg of BW(-1).d(-1) vs. high Se; 80 microg of Se.kg of BW(-1).d(-1)). Selenium treatments were initiated 21 d before breeding, and nutritional treatments were initiated on d 64 of gestation. Diets (DM basis) were 16% CP and 2.12 Mcal/kg of ME. In Exp. 1, Se15 increased (P = 0.07) vascular endothelial growth factor (VEGF) mRNA expression, whereas Se supplementation decreased (P = 0.06) kinase insert domain receptor (KDR) mRNA in maternal mucosal scrape on d 134 of gestation. Expression of VEGF mRNA was decreased by Se (P = 0.10) in fetal jejunum. In mammary tissue, fms-related tyrosine kinase 1 and KDR mRNA were greater in Se-wheat compared with Se3, and KDR expression was increased (P = 0.10) in Se15 compared with Se3. In Exp. 2, dietary restriction increased (P < or = 0.07) expression of mRNA for VEGF, fms-related tyrosine kinase 1, KDR, neuropilin 1, neuropilin 2, and hypoxia-inducible factor 1, alpha subunit in mucosal scrapes from maternal jejunum. In fetal jejunum, soluble guanylate cyclase, was decreased (P = 0.01) by maternal dietary restriction from d 64 to 135 of gestation. Total microvascularity in fetal jejunum was reduced (P = 0.002) by maternal dietary restriction. Mammary gland expression of VEGF, neuropilin 1, angiopoietin receptor (endothelial tyrosine kinase), and endothelial nitric oxide synthase 3 increased (P < or = 0.09), whereas angiopoietin 1 decreased (P = 0.05) due to nutrient restriction. Data indicate that expression of angiogenic factors and receptors in maternal intestine, mammary gland, and fetal jejunum are responsive to maternal nutrition and likely explain observed changes in tissue vascularity.
本研究的目的是评估母体饮食限制和硒供应对肠道和乳腺组织中血管生成因子mRNA表达、以及晚期胎儿肠道空肠隐窝细胞增殖和血管形成的影响。在实验1中，将怀孕的母羊羔羊（n = 32；初始体重 = 45.6 ± 2.3 kg）随机分配到4种处理中的1种。处理（在妊娠50 ± 5天开始）分别为对照（3.5 μg硒·kg体重⁻¹·天⁻¹）、硒小麦（75 μg硒·kg体重⁻¹·天⁻¹）、硒酸盐（Se3；提供75 μg硒·kg体重⁻¹·天⁻¹）、硒酸盐（Se15；提供375 μg硒·kg体重⁻¹·天⁻¹）。日粮（以干物质计）的粗蛋白（CP）含量（15.5%）和代谢能（ME）含量（2.68 Mcal/kg）相似。在实验2中，将怀孕的母羊羔羊（n = 36；初始体重53.8 ± 1.3 kg）随机分配到一个2×2析因设计的处理中。因素为营养（对照，满足100%需求 vs. 营养限制，对照的60%）和日粮硒（充足硒；6 μg硒·kg体重⁻¹·天⁻¹ vs. 高硒；80 μg硒·kg体重⁻¹·天⁻¹）。硒处理在配种前21天开始，营养处理在妊娠64天开始。日粮（以干物质计）的粗蛋白含量为16%，代谢能含量为2.12 Mcal/kg。在实验1中，Se15增加了（P = 0.07）血管内皮生长因子（VEGF）mRNA的表达，而在妊娠134天时，补充硒降低了（P = 0.06）母体黏膜刮片中激酶插入结构域受体（KDR）mRNA的表达。在胎儿空肠中，硒降低了（P = 0.10）VEGF mRNA的表达。在乳腺组织中，与Se3相比，硒小麦组中fms相关酪氨酸激酶1和KDR mRNA的表达更高，与Se3相比，Se15组中KDR的表达增加了（P = 0.10）。在实验2中，饮食限制增加了（P≤0.07）母体空肠黏膜刮片中VEGF、fms相关酪氨酸激酶1、KDR、神经纤毛蛋白1、神经纤毛蛋白2和缺氧诱导因子1α亚基mRNA的表达。在胎儿空肠中，从妊娠64天到135天，母体饮食限制降低了（P = 0.01）可溶性鸟苷酸环化酶的表达。母体饮食限制降低了（P = 0.002）胎儿空肠中的总微血管密度。由于营养限制，乳腺中VEGF、神经纤毛蛋白1、血管生成素受体（内皮酪氨酸激酶）和内皮型一氧化氮合酶3的表达增加（P≤0.09），而血管生成素1的表达降低（P = 0.05）。数据表明，母体肠道、乳腺和胎儿空肠中血管生成因子和受体的表达对母体营养有反应，这可能解释了观察到的组织血管变化。
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