Placental BDNF/TrkB Signaling System is Modulated by Fetal Growth Disturbances in Rat and Human
Placental BDNF/TrkB Signaling System is Modulated by Fetal Growth Disturbances in Rat and Human
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DOI：
10.1016/j.placenta.2010.06.008
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发表时间：
2010-09-01
期刊：
影响因子：
3.8
通讯作者：
Lesage, J.
中科院分区：
文献类型：
--
作者：
Mayeur, S.;Silhol, M.;Lesage, J.
脑源性神经营养因子（BDNF）在小鼠着床、胎盘发育和胎儿生长控制中发挥重要作用。其表达与神经系统等组织的营养状况密切相关。在之前的一项研究中，我们证明了母体营养不良（MU）在围产期会改变生长受限大鼠后代大脑中BDNF及其功能受体酪氨酸激酶受体B （TrkB）基因的表达，这表明这些早期的改变可能会产生长期的影响。在本研究中，我们测量了在妊娠期间食物限制50%的母亲的大鼠胎盘中BDNF/TrkB mRNA和蛋白质水平，以及在胎儿生长限制或胎儿巨大儿的妊娠中人类胎盘中的BDNF/TrkB mRNA和蛋白质水平。在大鼠中，已经鉴定出胎盘TrkB受体的两个亚型：TrkB- fl和TrkB- t1受体。我们发现，MU诱导足月胎儿宫内生长受限（IUGR），降低胎盘BDNF mRNA和蛋白水平。来自营养不良母亲的胎盘显示TrkB-FL mRNA表达增加，而TrkB-FL和TrkB-T1受体蛋白水平没有改变。在IUGR胎盘中，BDNF和TrkB受体mRNA的表达均上调。最后，虽然BDNF和TrkB mRNA水平均未因胎儿巨大儿而改变。当巨大儿与母亲1型糖尿病相关时，BDNF mRNA水平降低。这些结果表明，大鼠和人类胎盘BDNF/TrkB系统在胎儿生长扰动期间受到调节，并受到母体能量状态的影响。这些数据表明，该系统可能在胎儿-胎盘单位发育中发挥重要作用，也可能与胎盘和胎儿生长障碍相关病理的病因学有关。(C) 2010 Elsevier Ltd.版权所有。
The brain-derived neurotrophic factor (BDNF) has been shown to exert an important role during implantation, placental development, and fetal growth control in mice. Its expression is closely related to the nutritional status in several tissues such as in the nervous system. In a previous study, we demonstrated that maternal undernutrition (MU), during the perinatal life, modified both the BDNF and its functional receptor, the tyrosine kinase receptor B (TrkB) gene expression in the brain of growth-restricted rat offspring during sensitive developmental windows, suggesting that these early modifications may have long-lasting consequences. In the present study, we measured BDNF/TrkB mRNA and protein levels in rat placentas from mothers submitted to a 50% food restriction during gestation, and in human placentas from pregnancies with fetal growth restriction or fetal macrosomia. In the rat, two subtypes of placental TrkB receptors have been identified: the TrkB-FL and TrkB-T1 receptors. We found that MU induced intrauterine growth restriction (IUGR) of fetuses at term and decreased the placental BDNF mRNA and protein levels. Placentae from undernourished mothers exhibited an increased mRNA expression of TrkB-FL whereas both TrkB-FL and TrkB-T1 receptors proteins levels were not modified. In human IUGR placentas, both BDNF and TrkB receptor mRNA expressions were up-regulated. Finally, although neither BDNF nor TrkB mRNA levels were altered by fetal macrosomia alone. BDNF mRNA levels were decreased when macrosomia was associated with maternal type 1 diabetes. These results show that the placental BDNF/TrkB system is modulated in rats and humans during pregnancies with fetal growth perturbations and is affected by the maternal energetic status. These data suggest that this system may exert an important role for the feto-placental unit development and that it may also be implicated in the etiology of pathologies related to placental and fetal growth disturbances. (C) 2010 Elsevier Ltd. All rights reserved.