Dong Feng, Ford Stephen P, Nijland Mark J, Nathanielsz Peter W, Ren Jun
Division of Pharmaceutical Sciences, University of Wyoming, Laramie, WY 82071, USA.
J Nutr Biochem. 2008 Jun;19(6):409-14. doi: 10.1016/j.jnutbio.2007.06.003. Epub 2007 Sep 14.
Intrauterine nutrition status is reported to correlate with risk of cardiovascular diseases in adulthood. Either under- or overnutrition during early to mid gestation contributes to altered fetal growth and ventricular geometry. This study was designed to examine myocardial expression of ciliary neurotrophic factor receptor alpha (CNTFRalpha) and its downstream mediator signal transducer and activator of transcription 3 (STAT3) on maternal undernutrition- or overnutrition-induced changes in fetal heart weight. Multiparous ewes were fed with 50% [nutrient-restricted (NR)], 100% (control) or 150% [overfed (OF)] of National Research Council requirements from 28 to 78 days of gestation (dG; term, 148 dG). Ewes were euthanized on Day 78, and the gravid uteri and fetuses recovered. Ventricular protein expression of CNTFRalpha, STAT3, phosphorylated STAT3, insulin-like growth factor I receptor (IGF-1R), and IGF binding protein 3 (IGFBP3) were quantitated using Western blot. Plasma cortisol levels were higher in both NR and OF fetuses, whereas plasma IGF-1 levels were lower and higher in NR and OF fetuses. Fetal weights were reduced by 29.9% in NR ewes and were increased by 22.2% in fetuses from OF ewes compared to control group. Nutrient restriction did not affect fetal heart or ventricular weights, whereas overfeeding increased heart and ventricular weights. Protein expression of CNTFRalpha in fetal ventricular tissue was reduced in OF group, whereas STAT3 and phosphorylated STAT3 levels were reduced in both NR and OF groups. Expression of IGF-1R and IGFBP3 was unaffected in either NR or OF group. These data suggested that, compared with maternal undernutrition, intrauterine overfeeding during early to mid gestation is associated with increases in fetal blood concentrations of cortisol and IGF-1, in association with ventricular hypertrophy where reduced expression of CNTFRalpha and STAT3 may play a role.
据报道，子宫内营养状况与成年后患心血管疾病的风险相关。妊娠早期至中期的营养不足或营养过剩都会导致胎儿生长和心室形态改变。本研究旨在检测睫状神经营养因子受体α（CNTFRα）及其下游介质信号转导和转录激活因子3（STAT3）在母体营养不足或营养过剩引起的胎儿心脏重量变化中的心肌表达。经产母羊在妊娠28至78天（妊娠期，足月为148天）按照美国国家研究委员会要求的50%[营养限制（NR）]、100%（对照）或150%[过度喂养（OF）]进行喂养。在第78天对母羊实施安乐死，并取出妊娠子宫和胎儿。使用蛋白质免疫印迹法对心室中CNTFRα、STAT3、磷酸化STAT3、胰岛素样生长因子I受体（IGF-1R）和IGF结合蛋白3（IGFBP3）的蛋白质表达进行定量分析。NR组和OF组胎儿的血浆皮质醇水平均较高，而NR组胎儿的血浆IGF-1水平较低，OF组胎儿的血浆IGF-1水平较高。与对照组相比，NR组母羊所产胎儿体重降低了29.9%，OF组母羊所产胎儿体重增加了22.2%。营养限制不影响胎儿心脏或心室重量，而过度喂养则增加了心脏和心室重量。OF组胎儿心室组织中CNTFRα的蛋白质表达降低，而NR组和OF组中STAT3和磷酸化STAT3水平均降低。NR组和OF组中IGF-1R和IGFBP3的表达均未受影响。这些数据表明，与母体营养不足相比，妊娠早期至中期子宫内过度喂养与胎儿血液中皮质醇和IGF-1浓度升高有关，同时伴有心室肥大，其中CNTFRα和STAT3表达降低可能起了一定作用。
