Oxidative DNA damage in placentas from normal and pre-eclamptic pregnancies

Abstract

Placental oxidative stress was suggested to play a role in the pathogenesis of pre-eclampsia (PE). In this study, levels of 8-hydroxy-2'-deoxyguanosine (8-OH-dG), a well-established marker of oxidative DNA damage, were analysed in placental cellular DNA from normal (group NP) and pre-eclamptic (group PE) pregnancies as well as from PE pregnancies complicated by intrauterine growth restriction (group PE-IUGR). Placental samples obtained immediately after delivery were frozen at -80 degrees C until analysis. Cellular DNA was isolated, hydrolysed and analysed using high-performance liquid chromatography. Native nucleosides were monitored at 254 nm and 8-OH-dG using electrochemical detection. Concentrations of 8-OH-dG were expressed as micro mol/mol 2'-deoxyguanosine. In group NP, mean concentration of 8-OH-dG reached 179.97+/-80.58 (+/-SEM; micro mol/mol dG). 8-OH-dG levels were higher in group PE (273.44+/-110.14 micro mol/mol), but the difference was not significant in comparison with group NP. Highest concentrations of 8-OH-dG were found in group PE-IUGR (428.97+/-141.40 micro mol/mol), with levels significantly higher than in group NP, but not group PE. The results indicate a positive correlation between the severity of PE and the degree of oxidative stress and corroborate previous studies suggesting reactive oxygen species to be involved in the pathophysiology of PE.

Oxidative stress in pregnancy and fertility pathologies

“…Other studies on the same subject showed similar conclusions, with oxidative stress levels being higher in the groups that exhibit both pathologies (Fujimaki et al 2011;Mert et al 2012). These findings suggest a correlation be-tween the severity of the deficiency in the interaction between cytotrophoblasts and the maternal spiral arteries, both representative of IUGR and PE, and the levels of oxidative stress (Wiktor et al 2004).…”

“…The PE plus IUGR group presented the highest 8-OHdG levels, with a significant difference from control. The PE group, however, showed no statistically significant difference from control (Wiktor et al 2004). Other studies on the same subject showed similar conclusions, with oxidative stress levels being higher in the groups that exhibit both pathologies (Fujimaki et al 2011;Mert et al 2012).…”

“…Despite having distinctive clinical manifestations, there is accumulating evidence that the two pathologies have a common cause: an abnormal placental implantation (Mert et al 2012). Several studies have been conducted in order to understand if the two pathologies are related (Fujimaki et al 2011;Mert et al 2012;Takagi et al 2004;Wiktor et al 2004). One study, using immunohistochemistry and Western blotting in tissue samples from normal and PE placentas, suggested that the oxidative damage was higher in placenta displaying PE together with IUGR when compared with placenta displaying PE alone (Takagi et al 2004).…”

Absence of telomere shortening and oxidative DNA damage in the young adult offspring of women with pre-gestational type 1 diabetes

“…Type 1 diabetes offers a very hostile intrauterine environment, and is associated with high rates of fetal morbidity, including increased risks of congenital malformation, spontaneous abortion and perinatal death [39]. The fetal morbidity associated with maternal diabetes (and other embryopathies) reflects increased intrauterine oxidative stress and fetal oxidative DNA damage [11,12,[17][18][19][20][21][22][23][24]. The increased fetal DNA damage described in diabetes pregnancy must lead to increased telomeric DNA damage, as the GGG sequence in telomeric DNA is particularly susceptible to DNA damage [17].…”

“…Rates of telomere shortening at cell division are highly dependent on oxidatively induced strand breaks in telomeric DNA and oxidative DNA damage [11,12,17,18]. Feto-placental telomere attrition is an attractive hypothetical bridge between the adverse intrauterine environment and preprogramming of the offspring towards senescent phenotypes [19][20][21], as an adverse intrauterine environment increases oxidative damage to feto-placental DNA and fetal vascular endothelium [22][23][24]. We have previously suggested that this mechanism could account for a senescent phenotype in the adult offspring of women with type 1 diabetes [25].…”