Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal.
Unit of Biochemistry, Department of Biomedicine, Faculty of Medicine, University of Porto, Porto, Portugal; Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, Portugal.
Reprod Biol. 2022 Mar;22(1):100602. doi: 10.1016/j.repbio.2022.100602. Epub 2022 Jan 10.
Extravillous trophoblasts (EVTs) are the main participants in the process of placentation, an early process critical for placental growth and function involving an adequate invasion and complete remodelling of the maternal spiral arteries during early pregnancy. An increase in oxidative stress during pregnancy is associated with the onset and progression of several pregnancy disorders, including preeclampsia and gestational diabetes mellitus and it also occurs due to exposure of pregnant women to some xenobiotics (eg. alcohol). This study aimed to investigate how oxidative stress affects EVTs, and the ability of several distinct antioxidant agents to prevent these changes. For this, we exposed HTR8/SVneo cells to tert-butylhydroperoxide (0.5 μM; 24 h), which was able to increase lipid peroxidation and protein carbonyl levels. Under these conditions, there was a decrease in proliferation rates, culture growth, migratory and angiogenic capacities and an increase in the apoptosis rates. The antiproliferative effect of TBH was supressed by simultaneous treatment of the cells with α-tocopherol, but other antioxidants (vitamin C, allopurinol, apocynin, N-acetylcysteine, quercetin and resveratrol) were ineffective. α-tocopherol was also able to abolish the effect of TBH on lipid peroxidation and protein carbonyl levels. Overall, our results show that oxidative stress interferes with EVT characteristics essential for the placentation process, which may contribute to the association between oxidative stress and pregnancy disorders. Our results also show that the nature of the in vitro model of oxidative stress-induction is an important determinant of the cellular consequences of oxidative stress and, therefore, of the efficacy of antioxidants.
绒毛外滋养细胞（EVTs）是胎盘形成过程中的主要参与者，这是一个早期过程，对于胎盘的生长和功能至关重要，包括在妊娠早期充分浸润和完全重塑母体螺旋动脉。妊娠期间氧化应激的增加与几种妊娠疾病的发生和进展有关，包括子痫前期和妊娠期糖尿病，并且还由于孕妇暴露于某些外源性物质（例如酒精）而发生。本研究旨在研究氧化应激如何影响 EVTs，以及几种不同抗氧化剂预防这些变化的能力。为此，我们将 HTR8/SVneo 细胞暴露于叔丁基过氧化物（0.5 μM；24 小时）中，这能够增加脂质过氧化和蛋白质羰基水平。在这些条件下，增殖率、培养生长、迁移和血管生成能力下降，凋亡率增加。TBH 的抗增殖作用通过同时用α-生育酚处理细胞而被抑制，但其他抗氧化剂（维生素 C、别嘌呤醇、apocynin、N-乙酰半胱氨酸、槲皮素和白藜芦醇）无效。α-生育酚还能够消除 TBH 对脂质过氧化和蛋白质羰基水平的影响。总的来说，我们的结果表明，氧化应激干扰了对胎盘形成过程至关重要的 EVT 特征，这可能与氧化应激和妊娠疾病之间的关联有关。我们的结果还表明，诱导氧化应激的体外模型的性质是氧化应激的细胞后果以及抗氧化剂的功效的重要决定因素。
