Trophoblast Differentiation Affects Crucial Nutritive Functions of Placental Membrane Transporters.
Trophoblast Differentiation Affects Crucial Nutritive Functions of Placental Membrane Transporters.
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滋养细胞分化影响胎盘膜转运蛋白的重要营养功能。
DOI：
10.3389/fcell.2022.820286
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发表时间：
2022
影响因子：
5.5
通讯作者：
Albrecht C
中科院分区：
文献类型：
--
作者：
Karahoda R;Zaugg J;Fuenzalida B;Kallol S;Moser-Haessig R;Staud F;Albrecht C
细胞滋养层细胞是增殖和融合形成多核合体滋养层的前体细胞，参与胎盘的内分泌和运输功能。虽然膜转运蛋白在母胎界面的营养物质、激素和外源物质的分布中起着关键作用，但它们对合体滋养层的选择性却很差。我们的目的是评估胎盘转运蛋白在体外对滋养层细胞分化的调节作用。在分离的原代人滋养层细胞中进行合胞化前后的实验。采用定量聚合酶链式反应技术对6个分子标记和30个膜转运蛋白的基因表达进行了研究。随后，对参与经胎盘转运必需营养素的蛋白质的功能表达进行了评估，即胆固醇(ABCA1，Abcg1)、葡萄糖(SLC2A1)、亮氨酸(SLC3A2，SLC7A5)和铁(转铁蛋白受体，TfR1)。我们发现人绒毛膜促性腺激素、胎盘催乳素、endoglin和钙粘素-11是合胞化过程的最佳基因标记物。我们发现，滋养层细胞的分化与几种营养和药物转运蛋白的差异基因表达(主要是上调)有关。此外，我们还发现在合体细胞中Abcg1、SLC3A2、SLC7A5和TfR1的蛋白表达和活性增强，而ABCA1和GLUT1没有变化。综上所述，这些结果表明合体滋养层细胞在运输必需营养物质胆固醇、亮氨酸和铁方面起着主导作用。尽管如此，我们提出的证据表明，细胞滋养层细胞也可能与对细胞融合过程至关重要的运输功能有关。我们的发现共同为与滋养细胞融合相关的细胞功能或被滋养细胞融合改变的细胞功能提供了新的见解。重要的是，缺陷的合胞化可能会导致营养转移失衡，最终损害胎儿的发育和编程。
Cytotrophoblasts are progenitor cells that proliferate and fuse to form the multinucleated syncytiotrophoblast layer, implicated in placental endocrine and transport functions. While membrane transporters play a critical role in the distribution of nutrients, hormones, and xenobiotics at the maternal-fetal interface, their selectivity to the syncytiotrophoblast layer is poorly characterized. We aimed to evaluate the regulation of placental transporters in response to trophoblast differentiation in vitro. Experiments were carried out in isolated primary human trophoblast cells before and after syncytialization. Gene expression of six molecular markers and thirty membrane transporters was investigated by qPCR analysis. Subsequently, functional expression was evaluated for proteins involved in the transplacental transfer of essential nutrients i.e., cholesterol (ABCA1, ABCG1), glucose (SLC2A1), leucine (SLC3A2, SLC7A5), and iron (transferrin receptor, TfR1). We identified that human chorionic gonadotropin, placental lactogen, endoglin, and cadherin-11 serve as optimal gene markers for the syncytialization process. We showed that trophoblast differentiation was associated with differential gene expression (mostly up-regulation) of several nutrient and drug transporters. Further, we revealed enhanced protein expression and activity of ABCG1, SLC3A2, SLC7A5, and TfR1 in syncytialized cells, with ABCA1 and GLUT1 displaying no change. Taken together, these results indicate that the syncytiotrophoblast has a dominant role in transporting essential nutrients cholesterol, leucine, and iron. Nonetheless, we present evidence that the cytotrophoblast cells may also be linked to transport functions that could be critical for the cell fusion processes. Our findings collectively yield new insights into the cellular functions associated with or altered by the trophoblast fusion. Importantly, defective syncytialization could lead to nutrient transfer imbalance, ultimately compromising fetal development and programming.
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影响因子：
4.4
作者：
Huang X;Anderle P;Hostettler L;Baumann MU;Surbek DV;Ontsouka EC;Albrecht C
通讯作者：
Albrecht C
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
4.1
作者：
Gambling, L;Danzeisen, R;McArdle, HJ
通讯作者：
McArdle, HJ
影响因子：
3.8
作者：
Carter, AM
通讯作者：
Carter, AM
DOI：
10.1073/pnas.0902925106
发表时间：
2009-07-21
影响因子：
11.1
作者：
Dupressoir, Anne;Vernochet, Cecile;Heidmann, Thierry
通讯作者：
Heidmann, Thierry