Altered placental and fetal expression of IGFs and IGF-binding proteins associated with intrauterine growth restriction in fetal sheep during early and mid-pregnancy

Altered placental and fetal expression of IGFs and IGF-binding proteins associated with intrauterine growth restriction in fetal sheep during early and mid-pregnancy
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DOI:
10.1203/01.pdr.0000242364.78002.71
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发表时间:
2006-11-01
期刊:
影响因子:
3.6
通讯作者:
Regnault, Timothy R. H.
Regnault, Timothy R. H.
中科院分区:
医学3区
文献类型:
--
作者:
De Vrijer, Barbra;Davidsen, Meredith L.;Regnault, Timothy R. H.

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胰岛素样生长因子(IGFs)的改变与胎儿宫内生长受限(IUGR)的发生有关。目前的研究检查胎盘和胎儿肝脏的IGF系统的组件在两个时间点(55和90天胎龄,dGA;术语147 dGA)在高温(HT)诱导的羊胎盘inflicency-IUGR模型的mRNA浓度。母体血浆胰岛素和IGF-I在55和90 dGA时保持恒定,不受给药影响。脐静脉胰岛素浓度在HT暴露后90 dGA时趋于降低。在HT胎盘中,90 dGA时肉阜IGF-I mRNA增加(p < 0.05),而子叶浓度在整个妊娠期间保持不变,并且不受处理的影响。在对照子叶中,在55和90 dGA之间,IGF-II mRNA浓度增加(p < 0.01),IGFBP-3浓度降低(p < 0.01)。HT胎盘子叶IGF-II和肉阜IGFBP-4 mRNA在55 dGA时显著高于对照组(p < 0.01和p < 0.05)。胎肝IGF-I。IGFBP-2、IGFBP-3和IGFBP-4的浓度在妊娠期间升高(p < 0.05)。但没有治疗效果。这些数据表明,在妊娠早期和中期胎盘IGF表达的变化可能使妊娠胎盘功能不全,导致在妊娠后期发育胎儿的底物供应不足。
The insulin-like growth factors (IGFs) are postulated to be altered in association with the development of intrauterine growth restriction (IUGR). The present studies examined placental and fetal hepatic mRNA concentration of components of the IGF system at two time points (55 and 90 d gestational age, dGA; Term 147 dGA) in a hyperthermia (HT)-induced sheep model of placental insufficiency-IUGR. Maternal plasma insulin and IGF-I were constant at 55 and 90 dGA and were unaffected by treatment. Umbilical vein insulin concentrations tended to be reduced at 90 dGA following HT exposure. Caruncle IGF-I mRNA was increased at 90 dGA in HT placentae (p < 0.05), while cotyledon concentrations were constant over gestation and unaltered by treatment. In control cotyledons, IGF-II mRNA concentration increased (p < 0.01) and IGFBP-3 decreased between 55 and 90 dGA (p < 0.01). Cotyledon IGF-II and caruncle IGFBP-4 mRNA were elevated at 55 dGA in HT placentae compared with control (p < 0.01 And p < 0.05 respectively). Fetal hepatic IGF-I. IGFBP-2, -3 and -4 concentrations rose over gestation (p < 0.05). but there were no treatment effects. These data suggest that changes in placental IGF expression in early and mid gestation may predispose the pregnancy to placental insufficiency, resulting in inadequate substrate supply to the developing fetus later in gestation.