Organic Cation Transporter 3 (OCT3/SLC22A3) and Multidrug and Toxin Extrusion 1 (MATE1/SLC47A1) Transporter in the Placenta and Fetal Tissues: Expression Profile and Fetus Protective Role at Different Stages of Gestation
Organic Cation Transporter 3 (OCT3/SLC22A3) and Multidrug and Toxin Extrusion 1 (MATE1/SLC47A1) Transporter in the Placenta and Fetal Tissues: Expression Profile and Fetus Protective Role at Different Stages of Gestation
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DOI：
10.1095/biolreprod.112.105064
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发表时间：
2013-03-01
影响因子：
3.6
通讯作者：
Staud, Frantisek
中科院分区：
文献类型：
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作者：
Ahmadimoghaddam, Davoud;Zemankova, Lenka;Staud, Frantisek
在我们以前的研究中，我们描述了有机阳离子转运蛋白3的同步活性，（OCT 3/SLC 22 A3）和多药和毒素外排1（MATE 1/SLC 47 A1）转运蛋白在有机阳离子通过大鼠胎盘中的作用及其在胎儿防御中的作用;在这项研究中，我们假设在整个妊娠过程中，胎盘中OCT 3和MATE 1水平的变化可能会影响胎儿保护和解毒。采用定量RT-PCR、Western blot分析和免疫组化方法，我们能够检测到Oct 3/OCT 3和Mate 1/MATE 1在大鼠胎盘中的表达，早在妊娠第12天（gd），随着妊娠结束，表达呈增加趋势。比较早期和晚期妊娠人胎盘，我们观察到OCT 1的稳定表达和OCT 2和OCT 3亚型的表达下降。与目前的文献相反，我们也能够在人胎盘中检测到MATE 1/MATE 2亚型，然而，具有相当大的个体间和个体内变异性。通过将OCT和MATE转运蛋白的底物1-甲基-4-苯基吡啶（MPP+）注入妊娠母鼠，我们研究了不同gds时胎盘对有机阳离子的保护功能。妊娠第12天，MPP+到达胎儿的量最多，而从妊娠第15天开始，MPP+从母体到胎儿的转运显着减少。我们得出结论，胎盘OCT 3和MATE 1的表达增加沿着胎盘组织的一般成熟，导致MPP+从母体到胎儿的转运显著降低。相反，人胎盘中OCT 3和MATE 1的表达降低表明这些转运蛋白可能在妊娠早期优先发挥胎儿保护作用。
In our previous study, we described synchronized activity of organic cation transporter 3 (OCT3/SLC22A3) and multidrug and toxin extrusion 1 (MATE1/SLC47A1) transporter in the passage of organic cations across the rat placenta and the role of these transporters in fetal defense; in this study, we hypothesized that changes in placental levels of OCT3 and MATE1 throughout gestation might affect the fetal protection and detoxification. Using quantitative RT-PCR, Western blot analysis, and immunohistochemistry, we were able to detect Oct3/OCT3 and Mate1/MATE1 expression in the rat placenta as early as on Gestation Day (gd) 12 with increasing tendency toward the end of pregnancy. Comparing first versus third trimester human placenta, we observed stable expression of OCT1 and decreasing expression of OCT2 and OCT3 isoforms. Contrary to the current literature, we were able to detect also MATE1/MATE2 isoforms in the human placenta, however, with considerable inter-and intraindividual variability. Using infusion of 1-methyl-4-phenyl-pyridinium (MPP+), a substrate of OCT and MATE transporters, into pregnant dams, we investigated the protective function of the placenta against organic cations at different gds. The highest amount of MPP+ reached the fetus on gd 12 while from gd 15 onward, maternal-to-fetal transport of MPP+ decreased significantly. We conclude that increased expression of placental OCT3 and MATE1 along with general maturation of the placental tissues results in significantly lower transport of MPP+ from mother to fetus. In contrast, decreasing expression of OCT3 and MATE1 in human placenta indicates these transporters may play a role in fetal protection preferentially at earlier stages of gestation.