Department of Public Health, Section of Environmental Health, University of Copenhagen, Copenhagen, Denmark.
Department of Clinical Medicine, Translational Neuropsychiatry Unit, University of Aarhus, Aarhus, Denmark.
PLoS One. 2020 Jun 3;15(6):e0233979. doi: 10.1371/journal.pone.0233979. eCollection 2020.
Exposure to maternal stress during pregnancy can have adverse effects on the fetus, which has potential long-term effects on offspring´s development and health. We investigated the kinetics and metabolism of the hormones and amino acids: cortisol, cortisone, tryptophan and serotonin in the term placenta in an ex vivo human placental perfusion model. The placentas used in the experiments were donated from families participating in the Maternal Stress and Placental Function project with a known maternal stress background.
Cortisol, cortisone, tryptophan and serotonin were added simultaneously to the maternal side in the 6 hour ex vivo term human recirculating placental perfusion model, in four experimental set-ups: without inhibitors, with carbenoxolone -that inhibits cortisol metabolism into cortisone, with fluoxetine that inhibits the serotonin transporter, and with PCPA that inhibits metabolism of tryptophan into serotonin. The concentration of cortisol and cortisone, and tryptophan and serotonin were quantified using UPLC and HPLC-MS respectively.
Cortisol was rapidly metabolized into cortisone in the placenta, to a somewhat lesser degree when adding the inhibitor carbenoxolone, resulting in higher fetal exposure to cortisol. Serotonin was also rapidly metabolized in the placenta. When adding fluoxetine a peak of fetal serotonin levels was seen in the first hour of the perfusion. No effect was seen of the maternal stress levels on placental transport kinetics in this study.
Inhibiting the metabolism of cortisol in the placenta increased fetal exposure to cortisol as expected. Unexpectedly we saw an increased fetal exposure to serotonin when inhibiting the serotonin transporter, which may be related to the increased serotonin concentration on the maternal side of the placenta. No effect on placental kinetics were evident on maternal stress levels during the pregnancy as the majority of participating mothers had normal stress levels.
孕妇在怀孕期间接触到的压力会对胎儿产生不良影响，这可能对后代的发育和健康产生潜在的长期影响。我们在离体人胎盘灌注模型中研究了激素和氨基酸：皮质醇、皮质酮、色氨酸和 5-羟色胺在足月胎盘中的动力学和代谢。实验中使用的胎盘来自参与“母体应激与胎盘功能”项目的家庭，这些家庭的母亲应激背景已知。
在 6 小时的离体足月人再循环胎盘灌注模型中，同时将皮质醇、皮质酮、色氨酸和 5-羟色胺添加到母体侧，有四个实验设置：不加抑制剂、加 carbenoxolone 抑制皮质醇代谢为皮质酮、加氟西汀抑制 5-羟色胺转运体、加 PCPA 抑制色氨酸代谢为 5-羟色胺。使用 UPLC 和 HPLC-MS 分别定量皮质醇和皮质酮以及色氨酸和 5-羟色胺的浓度。
皮质醇在胎盘内迅速代谢为皮质酮，加入抑制剂 carbenoxolone 时程度稍低，导致胎儿暴露于皮质醇的程度更高。5-羟色胺也在胎盘内迅速代谢。当添加氟西汀时，在灌注的第一个小时可以看到胎儿 5-羟色胺水平的峰值。在这项研究中，没有观察到母体应激水平对胎盘转运动力学的影响。
抑制胎盘内皮质醇的代谢如预期那样增加了胎儿对皮质醇的暴露。出乎意料的是，当抑制 5-羟色胺转运体时，我们观察到胎儿对 5-羟色胺的暴露增加，这可能与胎盘母体侧 5-羟色胺浓度增加有关。在怀孕期间，母体应激水平对胎盘动力学没有明显影响，因为大多数参与的母亲应激水平正常。
