Differential effects of maternal nutrient restriction through pregnancy on kidney development and later blood pressure control in the resulting offspring

Differential effects of maternal nutrient restriction through pregnancy on kidney development and later blood pressure control in the resulting offspring
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DOI:
10.1152/ajpregu.00741.2007
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发表时间:
2008-07-01
影响因子:
2.8
通讯作者:
Olson, D. M.
Olson, D. M.
中科院分区:
医学3区
文献类型:
--
作者:
Brennan, K. A.;Kaufman, S.;Olson, D. M.

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母体在妊娠期间的营养调控导致后代血压改变的机制可能包括胎儿、新生儿和成人肾脏前列腺素(PG)合成、代谢和受体表达的变化。由于营养限制对肾脏PG合成和受体系统在肾发生与肾单位数量和血压的影响尚未在大鼠中进行评估,本研究探讨了减少母亲的食物摄入量的50%,通过怀孕对年轻的雄性大鼠随意的影响。在每个采样时间点使用6只对照喂养的母亲和8只营养限制的妊娠大鼠(具有单窝交配),其中大部分发生在肾发生期间。营养限制母鼠的后代从出生到3天体重较轻。这伴随着PGE(2)减少,肾脏变小长达14天。营养限制也降低了PG合成酶的mRNA表达,对PG受体的影响不大,并增加了肾发生过程中的降解酶和成人肾脏中的糖皮质激素受体的mRNA表达。这些mRNA的变化通常伴随着蛋白质的类似变化。肾单位数量也减少,从7天到成年时,血压(遥测测量)没有增加控制后代在黑暗中,活跃的时期。总之,母体营养限制抑制了后代的肾脏PG浓度,这与肾脏生长发育抑制和血压降低有关。
The mechanisms whereby maternal nutritional manipulation through pregnancy result in altered blood pressure in the offspring may include changes in fetal and newborn and adult renal prostaglandin (PG) synthesis, metabolism, and receptor expression. Since the postnatal effects of nutrient restriction on the renal PG synthesis and receptor system during nephrogenesis in conjunction with nephron numbers and blood pressure have not been evaluated in the rat, the present study examined the effect of reducing maternal food intake by 50% of ad libitum through pregnancy on young male rats. Six control-fed mothers and eight nutrient-restricted pregnant rats with single litter mates were used at each sampling time point, most of which occurred during nephrogenesis. Offspring of nutrient-restricted dams were lighter from birth to 3 days. This was accompanied by reduced PGE(2), with smaller kidneys up to 14 days. Nutrient restriction also decreased mRNA expression of the PG synthesis enzyme, had little effect on the PG receptors, and increased mRNA expression of the degradation enzyme during nephrogenesis and the glucocorticoid receptor in the adult kidney. These mRNA changes were normally accompanied by similar changes in protein. Nephron number was also reduced from 7 days up to adulthood when blood pressure (measured by telemetry) did not increase as much as in control offspring during the dark, active period. In conclusion, maternal nutrient restriction suppressed renal PG concentrations in the offspring, and this was associated with suppressed kidney growth and development and decreased blood pressure.