Increased DNA damage in patients with complete hydatidiform mole

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Abstract

The pathologic mechanisms underlying the gestational trophoblastic diseases are largely unexplored, but are thought to involve oxidative damage to the maternal vasculature and also to the placenta. In this study we have assessed the plasma levels of total antioxidant response (TAR) and the levels of endogenous DNA damage – determined by the comet assay – in peripheral blood lymphocytes from 13 women with complete hydatidiform mole (CHM) and compared these with those of 12 healthy pregnant controls and 10 healthy non-pregnant controls. Significantly lower mean levels of plasma TAR were found in patients with CHM compared with healthy pregnant controls (1.08 ± 0.29 versus 1.17 ± 0.14 mmol Trolox Eq/L, p < 0.05) and with healthy non-pregnant controls (1.08 ± 0.29 versus 1.38 ± 0.12 mmol Trolox Eq/L, p < 0.05). Significantly higher mean levels of endogenous DNA damage were observed in patients with CHM than in healthy pregnant controls (234.5 ± 50.74 versus 125.7 ± 45.4 AU, p < 0.05) or in healthy non-pregnant controls (234.5 ± 50.74 versus 104.0 ± 49.6 AU, p < 0.05).

We observed an inverse correlation between the plasma TAR and the levels of endogenous DNA damage (r = −0.64, p < 0.01), in that the levels of oxidative damage to the DNA were found to parallel the decrease in the plasma TAR in the CHM group. These results reveal a relationship between the extracellular and intracellular (as reflected by damage to the DNA) levels of oxidation. Our observations suggest that there is a link between the increased levels of oxidative stress and the increase in endogenous DNA damage seen in patients with CHM, as compared with those seen in normal pregnancy. However, the nature of this link, and whether it is direct or indirect, remains to be explored.

Section snippets

Background and aims

The gestational trophoblastic diseases (GTD) comprise a group of interrelated diseases arising from placental trophoblastic tissue after normal or abnormal fertilisation. The WHO classification of GTD includes hydatidiform mole (complete and partial), invasive mole, choriocarcinoma, placental site trophoblastic tumour, and miscellaneous and unclassified trophoblastic lesions [1]. Complete hydatidiform mole (CHM) is by far the most commonly observed variant and is a lesion of the placenta

Subjects

Thirty-five women were enrolled in this study. Of these, 12 were healthy women in the first trimester of pregnancy with a single viable foetus (mean gestational age 10.4 weeks as estimated by ultrasonography). Ten healthy non-pregnant women also participated as controls. The remaining 13 subjects had complete hydatidiform mole (CHM) (mean gestational age 10.1 weeks as estimated from the date of the last menstrual period). Diagnosis of CHM was based on histopathological examination of the molar

Comet assay

The demographic characteristics of the subjects are shown in Table 1. There were no differences in mean age, gestational age, gravidity, or parity between the subjects. Between groups, the endogenous levels of DNA damage in the peripheral blood lymphocytes, the plasma TAR, the plasma total peroxide levels and the OSI were found to be significantly different (all p-values < 0.001) according to the ANOVA test. As seen in Table 2, the DNA damage levels were significantly higher in the patients with

Discussion

It is well known that oxidative stress increases during normal pregnancy. The production of reactive oxygen species is enhanced due to the increased metabolic activity during pregnancy, and this increase is even greater when the pregnancy is complicated by conditions such as hypertension or diabetes mellitus [13], [15].

Recently we have shown that in complicated pregnancies (i.e. in preeclampsia or CHM) patients are subjected to higher levels of oxidative stress. This state of oxidative stress

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