Maternal dietary restriction and selenium supply alters messenger ribonucleic acid expression of angiogenic factors in maternal intestine, mammary gland, and fetal jejunal tissues during late gestation in pregnant ewe lambs

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 mu g of Se.kg of BW-1.d(-1)), Se-wheat (75 mu g of Se.kg of BW-1.d(-1)), selenate (Se3; providing 75 mu g of Se.kg of BW-1.d(-1)), selenate (Se15; providing 375 mu g 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 mu g of Se.kg of BW-1.d(-1) vs. high Se; 80 mu g 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 = 0.07) expression of mRNA for VEGF, fms-related tyrosine kinase 1, KDR, neuropilin 1, neuropilin 2, and hypoxia-inducible factor 1, a 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 = 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.