Chronic Protein Restriction in Mice Impacts Placental Function and Maternal Body Weight before Fetal Growth.
Chronic Protein Restriction in Mice Impacts Placental Function and Maternal Body Weight before Fetal Growth.
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小鼠的慢性蛋白质限制会影响胎儿生长前的胎盘功能和母亲体重。
DOI：
10.1371/journal.pone.0152227
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Hallgrímsson B
中科院分区：
文献类型：
--
作者：
Gonzalez PN;Gasperowicz M;Barbeito-Andrés J;Klenin N;Cross JC;Hallgrímsson B
资源分配机制对孕产妇和胎儿的生存至关重要，特别是在营养物质供应有限的情况下。我们研究了胎儿-胎盘发育对母亲慢性蛋白质营养不良的反应，以检验母亲低蛋白饮食导致胎盘和胎儿组织的不同生长限制以及胎盘的适应性变化可能减轻对胎儿生长的影响的假说。C57BL/6J雌性小鼠饲喂低蛋白饲料(6%蛋白质)和对照组等热量饲料(20%蛋白质)。在胚胎发育10.5天、17.5天和18.5天制备组织样本，进行形态计量学、组织学和定量RT-PCR分析，其中包括滋养层细胞亚型的标记。潜在的内分泌适应性通过催乳素相关激素基因的表达来评估。在低蛋白组，胎盘重量在E10.5时显著降低，随后母亲体重在E17.5时下降，而胎儿变得明显轻并不早于E18.5。低蛋白组胎头在E18.5，虽然比对照组小，但比预期的身体大小要大。E17.5对颅顶和颅底屈曲的相对大小和形状的影响较大，E18.5的影响更大。胎盘交界区是富含内分泌和储存能量的糖原细胞的一层，在低蛋白胎盘和糖原滋养层细胞标志物Pcdh12的表达较小。胎盘激素基因Pr13a1对低蛋白饮食的反应发生改变：胎盘激素基因Pr13a1在胚胎发育正常时于E17.5时表达升高，但在E18.5时随着胎儿生长的减慢而急剧下降。这一模型表明，营养物质优先用于维持胎儿和大脑的生长，胎盘是妊娠早期的营养感受器，在减轻母亲营养不良对胎儿生长的影响方面起到了作用。
Mechanisms of resource allocation are essential for maternal and fetal survival, particularly when the availability of nutrients is limited. We investigated the responses of feto-placental development to maternal chronic protein malnutrition to test the hypothesis that maternal low protein diet produces differential growth restriction of placental and fetal tissues, and adaptive changes in the placenta that may mitigate impacts on fetal growth. C57BL/6J female mice were fed either a low-protein diet (6% protein) or control isocaloric diet (20% protein). On embryonic days E10.5, 17.5 and 18.5 tissue samples were prepared for morphometric, histological and quantitative RT-PCR analyses, which included markers of trophoblast cell subtypes. Potential endocrine adaptations were assessed by the expression of Prolactin-related hormone genes. In the low protein group, placenta weight was significantly lower at E10.5, followed by reduction of maternal weight at E17.5, while the fetuses became significantly lighter no earlier than at E18.5. Fetal head at E18.5 in the low protein group, though smaller than controls, was larger than expected for body size. The relative size and shape of the cranial vault and the flexion of the cranial base was affected by E17.5 and more severely by E18.5. The junctional zone, a placenta layer rich in endocrine and energy storing glycogen cells, was smaller in low protein placentas as well as the expression of Pcdh12, a marker of glycogen trophoblast cells. Placental hormone gene Prl3a1 was altered in response to low protein diet: expression was elevated at E17.5 when fetuses were still growing normally, but dropped sharply by E18.5 in parallel with the slowing of fetal growth. This model suggests that nutrients are preferentially allocated to sustain fetal and brain growth and suggests the placenta as a nutrient sensor in early gestation with a role in mitigating impacts of poor maternal nutrition on fetal growth.