Maternal undernutrition and the offspring kidney: from fetal to adult life
Maternal undernutrition and the offspring kidney: from fetal to adult life
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DOI：
10.1590/s0100-879x2010007500113
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发表时间：
2010-11-01
影响因子：
2.3
通讯作者：
Boer, P.A.
中科院分区：
文献类型：
--
作者：
Mesquita, F.F.;Gontijo, J.A.R.;Boer, P.A.
妊娠期母体膳食蛋白质限制与低胎儿出生体重相关，并导致肾脏形态和生理变化。不同的机制可以导致这种表型：暴露于胎儿糖皮质激素，改变的组成部分，肾素-血管紧张素系统，细胞凋亡和DNA甲基化。妊娠期低蛋白饮食会降低胎盘11 β-羟基类固醇脱氢酶的活性，使胎儿暴露于糖皮质激素，并重置后代的下丘脑-垂体-肾上腺轴。在生命的任何时期，1型（AT 1（R））或2型（AT 2（R））AngII受体的异常功能/表达可能是肾适应的结果或原因。与对照组相比，在低蛋白饮食母亲所生后代出生后的第一天，AT 1（R）上调，但这种蛋白质似乎在12日龄及以后下调。在这些后代中，AT 2（R）表达在1日龄时与对照不同，但此后也下调，在所有年龄段均具有低肾单位数量：从胎儿期开始，在肾单位形成结束时，以及在成年期。然而，在成年期，由于肾小球和足细胞肥大，肾小球滤过率没有改变。肾小管转运蛋白受生理机制调节; Na+/K+-ATP酶受AngII抑制，在该模型中，下调的AngII受体无法抑制Na+/K+-ATP酶，导致Na+重吸收增加，导致高血压状态。我们还考虑了肾发生过程中促凋亡和抗凋亡因子的调节，因为器官发生依赖于增殖、分化和细胞死亡之间的紧密平衡。
Maternal dietary protein restriction during pregnancy is associated with low fetal birth weight and leads to renal morphological and physiological changes. Different mechanisms can contribute to this phenotype: exposure to fetal glucocorticoid, alterations in the components of the renin-angiotensin system, apoptosis, and DNA methylation. A low-protein diet during gestation decreases the activity of placental 11 beta-hydroxysteroid dehydrogenase, exposing the fetus to glucocorticoids and resetting the hypothalamic-pituitary-adrenal axis in the offspring. The abnormal function/expression of type 1 (AT1(R)) or type 2 (AT2(R)) AngII receptors during any period of life may be the consequence or cause of renal adaptation. AT1(R) is up-regulated, compared with control, on the first day after birth of offspring born to low-protein diet mothers, but this protein appears to be down-regulated by 12 days of age and thereafter. In these offspring, AT2(R) expression differs from control at 1 day of age, but is also down-regulated thereafter, with low nephron numbers at all ages: from the fetal period, at the end of nephron formation, and during adulthood. However, during adulthood, the glomerular filtration rate is not altered, due to glomerulus and podocyte hypertrophy. Kidney tubule transporters are regulated by physiological mechanisms; Na+/K+-ATPase is inhibited by AngII and, in this model, the down-regulated AngII receptors fail to inhibit Na+/K+-ATPase, leading to increased Na+ reabsorption, contributing to the hypertensive status. We also considered the modulation of pro-apoptotic and anti-apoptotic factors during nephrogenesis, since organogenesis depends upon a tight balance between proliferation, differentiation and cell death.