Spatial and temporal expression of folate-related transporters and metabolic enzymes during mouse placental development
Spatial and temporal expression of folate-related transporters and metabolic enzymes during mouse placental development
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DOI：
10.1016/j.placenta.2012.02.005
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发表时间：
2012-05-01
期刊：
影响因子：
3.8
通讯作者：
Watson, E. D.
中科院分区：
文献类型：
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作者：
Cherukad, J.;Wainwright, V.;Watson, E. D.
众所周知，母体叶酸缺乏会导致胎儿发育异常。然而，胎盘的发育和功能在多大程度上也依赖于叶酸的摄取和代谢仍不清楚。为了了解叶酸缺乏或叶酸代谢异常可能影响滋养细胞类型，我们完成了叶酸受体（Folr）的全面时空蛋白表达分析。叶酸转运蛋白（质子偶联叶酸受体[Slc46a1或PCFT]和还原叶酸载体-1 [Rfc1]）和叶酸代谢酶（5,10-亚甲基四氢叶酸还原酶[Mthfr]和蛋氨酸合成酶[Mtr]）在小鼠胎盘从发育早期（E8.5）到足月（E18.5）的组织学切片中的表达。我们观察到，最高水平的蛋白表达是在发育早期（E8.5-E10.5），在成熟胎盘的三个主要层形成之前，这表明叶酸的摄取和代谢可能是胎盘发育本身所必需的。正如预期的那样，负责营养运输的迷宫滋养细胞在整个妊娠期间表达这些蛋白质，包括排列在母体血液间隙的窦状滋养细胞巨细胞的强烈表达。其他滋养细胞巨细胞（TGC）亚型（顶叶- tgcs和管状- tgcs），其功能不包括营养运输，从E8.5开始表达叶酸转运蛋白和酶。值得注意的是，这些蛋白也在E12.5-E18.5的糖原滋养细胞中检测到，这表明这些细胞在叶酸摄取和代谢中起着新的作用。总之，这些数据提供的证据表明，叶酸可能是正常胎盘发育和功能所必需的，其可利用性或代谢紊乱可能导致对胎儿发育的继发性影响。(C) 2012 Elsevier Ltd.版权所有。
It is well understood that maternal folate deficiency can cause abnormal fetal development. However, the extent to which placental development and function are also dependent upon folate uptake and metabolism remains unclear. To understand which trophoblast cell types may be affected by folate deficiency or abnormal folate metabolism, we completed a comprehensive spatial and temporal protein expression analysis of folate receptor (Folr), folate transporters (proton-coupled folate receptor [Slc46a1 or PCFT] and reduced folate carrier-1 [Rfc1]) and folate metabolic enzymes (5,10-methylenetetrahydrofolate reductase [Mthfr] and methionine synthase [Mtr]) in histological sections of mouse placentas from early development (E8.5) until term (E18.5). We observed that the highest level of protein expression was during early development (E8.5-E10.5), prior to the formation of the three main layers of the mature placenta suggesting that folate uptake and metabolism may be required for placental development, itself. As expected, the labyrinth trophoblast cells, which are responsible for nutrient transport, expressed these proteins throughout pregnancy, including robust expression in the sinusoidal trophoblast giant cells that line the maternal blood spaces. Other trophoblast giant cell (TGC) subtypes (parietal-TGCs and canal-TGCs), whose function does not include nutrient transport, expressed folate transporters and enzymes from E8.5 onwards. Remarkably, these proteins were also detected in glycogen trophoblast cells from E12.5-E18.5 suggesting a new role in folate uptake and metabolism for these cells. Together, these data provide evidence that folate may be necessary for normal placental development and function, and perturbations in its availability or metabolism may lead to secondary effects on fetal development. (C) 2012 Elsevier Ltd. All rights reserved.