Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic.
Biol Reprod. 2013 Mar 7;88(3):55. doi: 10.1095/biolreprod.112.105064. Print 2013 Mar.
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-phenylpyridinium (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.
在我们之前的研究中，我们描述了有机阳离子转运体 3（OCT3/SLC22A3）和多药和毒素外排蛋白 1（MATE1/SLC47A1）转运体在有机阳离子穿过大鼠胎盘的过程中的同步活性，以及这些转运体在胎儿防御中的作用；在这项研究中，我们假设整个妊娠期间胎盘内 OCT3 和 MATE1 水平的变化可能会影响胎儿的保护和解毒作用。使用定量 RT-PCR、Western blot 分析和免疫组织化学，我们能够在妊娠第 12 天（gd）检测到大鼠胎盘中的 Oct3/OCT3 和 Mate1/MATE1 表达，并且随着妊娠末期的临近，其表达呈上升趋势。与当前文献相比，我们在人类胎盘中也观察到了 OCT1 的稳定表达和 OCT2 和 OCT3 同工型的表达减少。与当前文献相反，我们能够在人类胎盘中检测到 MATE1/MATE2 同工型，然而，其表达存在显著的个体间和个体内差异。通过将 1-甲基-4-苯基吡啶（MPP(+)），一种 OCT 和 MATE 转运体的底物，输注到妊娠母体中，我们研究了胎盘在不同 gd 时对有机阳离子的保护作用。MPP(+)到达胎儿的量在 gd 12 时最高，而从 gd 15 开始，MPP(+)从母体向胎儿的转运显著减少。我们得出结论，胎盘 OCT3 和 MATE1 的表达增加以及胎盘组织的普遍成熟导致 MPP(+)从母体向胎儿的转运显著减少。相反，人类胎盘中 OCT3 和 MATE1 的表达减少表明这些转运体可能在妊娠早期优先发挥胎儿保护作用。
