α-tocopherol prevents oxidative stress-induced proliferative dysfunction in first-trimester human placental (HTR-8/SVneo) cells

Abstract

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.

Keywords: Extravillous trophoblasts; Oxidative stress; Tert-butylhydroperoxide; α-tocopherol.