Zhu M J, Du M, Hess B W, Means W J, Nathanielsz P W, Ford S P
Center for the Study of Fetal Programming, University of Wyoming, 1000 E. University Avenue, Laramie, WY 82071, USA.
Placenta. 2007 Apr;28(4):361-8. doi: 10.1016/j.placenta.2006.04.005. Epub 2006 Jul 5.
This study evaluated the role of MAPK/ERK1/2 and/or PI3-K/Akt signaling pathways in modulating bovine placentomal vascularity in response to maternal nutrient restriction. Beef cows were randomly assigned to control fed (Control, n=15, 100% of requirements) or nutrient restricted (NR, n=15, 50% requirements) diets from day 30 to day 125 of gestation. Ten cows from each dietary group were necropsied on day 125 (approximately 45% gestation), and the remaining cows in each diet group were then fed control diets and necropsied on day 250 (approximately 90% gestation). At day 125 of gestation, NR cows exhibited increased (P=0.06) COT vascularity, improved (P<0.05) placentome efficiency (fetal weight/placentomal weight), and increased (P<0.05) phosphorylated Akt and ERK1/2 in COT arteries compared to Control cows. By day 250, however, treatment differences in COT vascularity and phosphorylated Akt and ERK1/2 in COT arteries were lost. On both gestational days, no treatment difference was observed in the levels of phosphorylated Akt or ERK1/2 in CAR arteries. CAR vascularity was similar across treatment on day 125, but tended to be greater (P<0.10) in NR than Control cows on day 250. These data suggest that conceptuses react to an early gestational nutrient restriction by up-regulating COT growth signaling pathways associated with angiogenesis, and that these compensations do not persist to term.
本研究评估了丝裂原活化蛋白激酶/细胞外信号调节激酶1/2(MAPK/ERK1/2)和/或磷脂酰肌醇-3激酶/蛋白激酶B(PI3-K/Akt)信号通路在调节母体营养限制条件下牛胎盘血管生成中的作用。从妊娠第30天至第125天,将肉牛随机分为对照组(Control,n = 15,满足100%营养需求)或营养限制组(NR,n = 15,满足50%营养需求)。在妊娠第125天(约妊娠45%)对每个饮食组的10头母牛进行剖检,然后将每个饮食组的其余母牛改喂对照日粮,并在妊娠第250天(约妊娠90%)进行剖检。与对照组母牛相比,在妊娠第125天,营养限制组母牛的绒毛叶毛细血管密度增加(P = 0.06),胎盘效率提高(P < 0.05)(胎儿体重/胎盘重量),绒毛叶动脉中磷酸化Akt和ERK1/2增加(P < 0.05)。然而,到妊娠第250天,绒毛叶毛细血管密度以及绒毛叶动脉中磷酸化Akt和ERK1/2的处理差异消失。在两个妊娠日,子宫动脉中磷酸化Akt或ERK1/2水平均未观察到处理差异。在妊娠第125天,各处理组的子宫动脉血管生成相似,但在妊娠第250天,营养限制组母牛的子宫动脉血管生成比对照组母牛有增加趋势(P < 0.10)。这些数据表明,孕体通过上调与血管生成相关的绒毛叶生长信号通路对妊娠早期的营养限制做出反应,并且这些补偿作用不会持续到足月。