Complex patterns of cell growth in the placenta in normal pregnancy and as adaptations to maternal diet restriction
Complex patterns of cell growth in the placenta in normal pregnancy and as adaptations to maternal diet restriction
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DOI：
10.1371/journal.pone.0226735
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发表时间：
2020-01-09
期刊：
影响因子：
3.7
通讯作者：
Cross, James C.
中科院分区：
文献类型：
--
作者：
Eaton, Malcolm;Davies, Alastair H.;Cross, James C.
小鼠胎盘发育的主要里程碑已被很好地描述，但我们的理解仅限于胎盘如何适应环境的破坏或变化。通过体视学和细胞周期标记的表达，我们发现胎盘在正常条件下不仅通过滋养细胞的增生生长，而且通过广泛的多倍体和细胞肥大生长。为了模拟慢性营养不良，在怀孕前和怀孕期间给母亲喂食低蛋白饮食，我们发现这个正常的程序被改变了，它受到胎儿性别的影响。男性胎儿在胚胎日(E) 18.5即足月前出现宫内生长受限（IUGR），而女性胎儿早在胚胎日(E) 16.5即出现宫内生长受限（IUGR）。这种差异与胎盘迷宫层大小的差异有关，迷宫层是营养和气体交换的场所。营养转运基因的上调暗示了功能的变化。连接区也受到影响，糖原滋养层细胞和海绵滋养层细胞均减少。这些变化与Phlda2表达增加和Egfr表达减少有关。多倍体是滋养层巨细胞（TGC）和海绵状滋养层细胞的正常特征。在低蛋白胎盘中，窦状- tgcs和海绵滋养细胞的倍性增加，而顶叶- tgcs的倍性没有增加。这些结果表明，胎盘在发育和功能方面经历了一系列变化，以应对母体不良饮食，我们解释其中许多变化旨在减轻对胎儿和母体健康的影响。
The major milestones in mouse placental development are well described, but our understanding is limited to how the placenta can adapt to damage or changes in the environment. By using stereology and expression of cell cycle markers, we found that the placenta grows under normal conditions not just by hyperplasia of trophoblast cells but also through extensive polyploidy and cell hypertrophy. In response to feeding a low protein diet to mothers prior to and during pregnancy, to mimic chronic malnutrition, we found that this normal program was altered and that it was influenced by the sex of the conceptus. Male fetuses showed intrauterine growth restriction (IUGR) by embryonic day (E) 18.5, just before term, whereas female fetuses showed IUGR as early as E16.5. This difference was correlated with differences in the size of the labyrinth layer of the placenta, the site of nutrient and gas exchange. Functional changes were implied based on up-regulation of nutrient transporter genes. The junctional zone was also affected, with a reduction in both glycogen trophoblast and spongiotrophoblast cells. These changes were associated with increased expression of Phlda2 and reduced expression of Egfr. Polyploidy, which results from endoreduplication, is a normal feature of trophoblast giant cells (TGC) but also spongiotrophoblast cells. Ploidy was increased in sinusoidal-TGCs and spongiotrophoblast cells, but not parietal-TGCs, in low protein placentas. These results indicate that the placenta undergoes a range of changes in development and function in response to poor maternal diet, many of which we interpret are aimed at mitigating the impacts on fetal and maternal health.