Maternal obesity and overnutrition alter fetal growth rate and cotyledonary vascularity and angiogenic factor expression in the ewe

Maternal obesity and overnutrition alter fetal growth rate and cotyledonary vascularity and angiogenic factor expression in the ewe
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DOI:
10.1152/ajpregu.00498.2009
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发表时间:
2010-07-01
影响因子:
2.8
通讯作者:
Ford, Stephen P.
Ford, Stephen P.
中科院分区:
医学3区
文献类型:
--
作者:
Ma, Yan;Zhu, Mei J.;Ford, Stephen P.

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Ma Y,Zhu MJ,Zhang L,Hein SM,Nathanielsz PW,福特SP.母亲肥胖和营养过剩改变母羊的胎儿生长率和子叶血管分布及血管生成因子表达。Am J Physiol Regul Integr Comp Physiol 299:R249-R258,2010年。首次发表于2010年4月28日; doi:10.1152/ajpregu.00498.2009。在妊娠绵羊中,母体:胎儿交换发生在由胎盘子叶和子宫阜组织组成的胎盘体上。最近,我们报道了在妊娠中期(MG),肥胖(OB)母羊[饲喂150%国家研究理事会(NRC)建议的饮食]的胎儿重量比对照(C)母羊(饲喂100% NRC建议的饮食)的胎儿重量高30%,但在妊娠晚期(LG)胎儿重量相似。经胎盘的营养交换依赖于胎盘血流,而胎盘血流本身又依赖于胎盘血管。目前的研究调查了所观察到的OB与C相比的初始更快和随后更慢的胎儿生长速率是否与子叶血管分布和血管生成因子(血管内皮生长因子、成纤维细胞生长因子-2、胎盘生长因子、血管生成素-1和-2)表达的变化相关。MG时,OB的子叶微动脉直径显著大于C(P < 0.05),而从MG到LG,C的微动脉直径增加(P < 0.05),OB的微动脉直径无变化。子叶动脉血管生成因子mRNA和蛋白表达较低MG时OB的血管生成因子mRNA水平显著高于C组(P < 0.05),从MG到LG,C组的血管生成因子mRNA水平一直较低,而MG时C组的血管生成因子mRNA水平较高,到LG时C组的血管生成因子mRNA水平逐渐下降,到MG时C组的血管生成因子mRNA水平接近OB组(P < 0.05)。而MG-LG降低的子叶动脉血管生成因子可能起到保护胎儿免于过度胎盘血管发育、增加母体营养输送和过度体重增加的作用。
Ma Y, Zhu MJ, Zhang L, Hein SM, Nathanielsz PW, Ford SP. Maternal obesity and overnutrition alter fetal growth rate and cotyledonary vascularity and angiogenic factor expression in the ewe. Am J Physiol Regul Integr Comp Physiol 299: R249-R258, 2010. First published April 28, 2010; doi: 10.1152/ajpregu.00498.2009.-In pregnant sheep, maternal: fetal exchange occurs across placentomes composed of placental cotyledonary and uterine caruncular tissues. Recently, we reported that fetal weights of obese (OB) ewes [fed a diet of 150% of National Research Council (NRC) recommendations] were similar to 30% greater than those of control (C) ewes (fed a diet 100% of NRC recommendations) at midgestation (MG), but fetal weights were similar in late gestation (LG). Transplacental nutrient exchange is dependent on placental blood flow, which itself is dependent on placental vascularity. The current study investigated whether the observed initial faster and subsequent slower fetal growth rate of OB compared with C was associated with changes in cotyledonary vascularity and expression of angiogenic factors (vascular endothelial growth factor, fibroblast growth factor-2, placental growth factor, angiopoietin-1 and -2). Cotyledonary arteriole diameters were markedly greater (P < 0.05) in OB than C ewes at MG, but while arteriole diameter of C ewes increased (P < 0.05) from MG to LG, they remained unchanged in OB ewes. Cotyledonary arterial angiogenic factors mRNA and protein expression were lower (P < 0.05) in OB than C ewes at MG and remained low from MG to LG. In contrast, mRNA levels of angiogenic factors in C ewes declined from high levels at MG to reach those of OB ewes by LG. The increase in cotyledonary arteriole diameter in early to MG may function to accelerate fetal growth rate in OB ewes, while the decreased cotyledonary arterial angiogenic factors from MG-LG may function to protect the fetus from excessive placental vascular development, increased maternal nutrient delivery, and excessive weight gain.