Department of Pharmacology and Toxicology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Department of Obstetrics and Gynecology, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Placenta. 2021 Jan 15;104:220-231. doi: 10.1016/j.placenta.2020.12.015. Epub 2021 Jan 2.
An increasing number of women becomes pregnant while suffering from chronic kidney disease (CKD). As a result of decreased renal function, uremic solutes circulate at high levels in the maternal circulation. This study aimed to acquire more knowledge about the placental transfer of uremic solutes across the human placenta.
Placental transfer was studied in healthy term placentas, via the ex vivo dual-side human cotyledon perfusion technique (closed-closed set-up for both maternal and fetal circulations). Uremic solute concentrations in maternal and fetal perfusates were measured via LC-MS/MS over 180 min of perfusion.
We found that the studied compounds demonstrated different degrees of placental transfer. Fetal-to-maternal perfusate ratios at t = 180 min were for anthranilic acid 1.00 ± 0.02, indole-3-acetic acid 0.47 ± 0.08, hippuric acid 0.36 ± 0.18, l-arabinitol 0.33 ± 0.04, indoxyl sulfate 0.33 ± 0.11, neopterin 0.28 ± 0.14 and kynurenic acid 0.13 ± 0.03. All uremic solutes studied also emerged in the perfusates when cotyledons were perfused in the absence of uremic solute concentrations added to the maternal reservoir. For kynurenin these concentrations were so high, it complicated the calculation of a transfer ratio for the exogenously administered compound.
After 180 min of exposure the extent of placental transfer differs substantially for the solutes studied, reflecting different transfer rates. Future studies should investigate to what extent specific uremic solutes reach the fetal circulation in vivo and how they may interfere with organ function and development of the unborn child.
越来越多的女性在患有慢性肾脏病（CKD）时怀孕。由于肾功能下降，尿毒症溶质在母体循环中以高水平循环。本研究旨在更深入地了解尿毒症溶质在人胎盘内的胎盘转运。
通过离体双侧人绒毛膜胎盘灌注技术（母体和胎儿循环均为封闭式设置）研究健康足月胎盘的胎盘转运。通过 LC-MS/MS 在灌注 180 分钟的过程中测量母体和胎儿灌流液中的尿毒症溶质浓度。
我们发现所研究的化合物表现出不同程度的胎盘转运。t=180 分钟时，胎儿-母体灌流液的比值分别为：邻氨基苯甲酸 1.00±0.02、吲哚-3-乙酸 0.47±0.08、马尿酸 0.36±0.18、L-阿拉伯糖醇 0.33±0.04、吲哚硫酸酯 0.33±0.11、新蝶呤 0.28±0.14 和犬尿氨酸 0.13±0.03。当胎盘在没有添加尿毒症溶质浓度的情况下进行灌注时，所有研究的尿毒症溶质也会出现在灌流液中。对于犬尿氨酸，其浓度非常高，这使得计算外源性给予的化合物的转移比变得复杂。
暴露 180 分钟后，研究的溶质的胎盘转运程度有很大差异，反映了不同的转运率。未来的研究应调查特定的尿毒症溶质在体内到达胎儿循环的程度以及它们如何干扰未出生婴儿的器官功能和发育。
