Palmitic Acid Impedes Extravillous Trophoblast Activity by Increasing MRP1 Expression and Function.
Palmitic Acid Impedes Extravillous Trophoblast Activity by Increasing MRP1 Expression and Function.
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DOI：
10.3390/biom12081162
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发表时间：
2022-08-22
期刊：
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
胎盘绒毛外滋养层细胞（EVT）的正常功能，负责子宫胎盘血管重塑，是至关重要的氧气和营养物质的充分输送到发育中的胎儿和正常的胎儿编程。EVT对螺旋动脉的增殖和侵袭依赖于足够的叶酸水平。多药耐药相关蛋白1（MRP 1）是一种外排转运蛋白，已知可从这些细胞中清除叶酸。我们假设棕榈酸增加了MRP 1介导的从EVT中清除叶酸，从而干扰了EVT在早期胎盘血管重塑中的作用。HTR-8/SVneo和Swan-71细胞（妊娠早期人EVT）分别在不存在或存在0.5 mM和0.7 mM棕榈酸的情况下生长72小时。软脂酸增加ABCC 1基因表达和MRP 1蛋白表达在两个细胞系。叶酸从细胞流出到培养基中的速率随着培养细胞中的迁移和侵袭功能的降低而增加。用N-乙酰半胱氨酸（NAC）治疗阻止了棕榈酸介导的MRP 1上调，并恢复了EVT的侵袭和迁移。最后，在Swan-71细胞的ABCC 1敲除亚系中，侵袭和迁移功能显著增加。这项研究中的新发现，即棕榈酸增加MRP 1介导的叶酸外排，提供了一个缺失的环节，有助于解释母体摄入饱和脂肪酸如何影响子宫内环境。
Normal function of placental extravillous trophoblasts (EVTs), which are responsible for uteroplacental vascular remodeling, is critical for adequate delivery of oxygen and nutrients to the developing fetus and normal fetal programming. Proliferation and invasion of spiral arteries by EVTs depends upon adequate levels of folate. Multidrug resistance-associated protein 1 (MRP1), which is an efflux transporter, is known to remove folate from these cells. We hypothesized that palmitic acid increases MRP1-mediated folate removal from EVTs, thereby interfering with EVTs’ role in early placental vascular remodeling. HTR-8/SVneo and Swan-71 cells, first trimester human EVTs, were grown in the absence or presence of 0.5 mM and 0.7 mM palmitic acid, respectively, for 72 h. Palmitic acid increased ABCC1 gene expression and MRP1 protein expression in both cell lines. The rate of folate efflux from the cells into the media increased with a decrease in migration and invasion functions in the cultured cells. Treatment with N-acetylcysteine (NAC) prevented the palmitic acid-mediated upregulation of MRP1 and restored invasion and migration in the EVTs. Finally, in an ABCC1 knockout subline of Swan-71 cells, there was a significant increase in invasion and migration functions. The novel finding in this study that palmitic acid increases MRP1-mediated folate efflux provides a missing link that helps to explain how maternal consumption of saturated fatty acids compromises the in utero environment.
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影响因子：
9.8
作者：
Labarrere CA;DiCarlo HL;Bammerlin E;Hardin JW;Kim YM;Chaemsaithong P;Haas DM;Kassab GS;Romero R
通讯作者：
Romero R
滋养细胞的分化会影响胎盘转运蛋白的关键营养功能。
影响因子：
5.5
作者：
Karahoda R;Zaugg J;Fuenzalida B;Kallol S;Moser-Haessig R;Staud F;Albrecht C
通讯作者：
Albrecht C
影响因子：
7.7
作者：
Brix, Nis;Ernst, Andreas;Ramlau-Hansen, Cecilia Host
通讯作者：
Ramlau-Hansen, Cecilia Host
影响因子：
4
作者：
Le, H. T.;Atif, J.;Beristain, A. G.
通讯作者：
Beristain, A. G.
影响因子：
3.6
作者：
Manuel, Clarence R.;Charron, Maureen J.;Reznik, Sandra E.
通讯作者：
Reznik, Sandra E.