Mitochondrial DNA copy number and oxidative DNA damage in placental tissues from gestational diabetes and control pregnancies: a pilot study

Abstract

Background: Available evidence supports the role of reactive oxygen species in the pathogenesis of placental insufficiency, gestational diabetes mellitus (GDM), and other pregnancy complications. Abnormal placental mitochondrial function resulting from reactive oxygen species may also be an important precedent of adverse perinatal outcomes.

Methods: We investigated the association of placental oxidative stress with placental mitochondrial DNA (mtDNA) copy number, an indicator of placental mitochondrial density and possible mitochondrial dysfunction, using samples collected from GDM cases and controls. 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, was measured in placentas of 19 GDM cases and 21 controls using a competitive immunoassay. Placental mtDNA copy number was determined using real-time quantitative PCR. Bivariate and multivariable linear regression procedures were used to evaluate associations of these two biomarkers.

Results: Placental DNA oxidation was positively associated with mtDNA copy number in both GDM and control placentas. After adjusting for maternal age, pre-pregnancy body mass index and gestational age at delivery, mtDNA copy number increased (beta = 67.0; 95% CI 27.8 - 106.2, p = 0.001) for every 0.1 ng/microg increase of placental 8-OHdG among GDM cases and controls.

Conclusions: These cross sectional data suggest an association of placental mtDNA copy number with oxidative stress. The consequences of placental oxidative stress and mitochondrial dysfunction on the course and outcomes of pregnancy remain to be elucidated in larger prospective studies.

Figure 1

Relationship between placental mitochondrial DNA (mtDNA) copy number and placental oxidative DNA damage in GDM (RED), control (BLUE) and the groups combined (GREEN). Total DNA isolated from placental tissues were quantified by real-time quantitative PCR analyses using the RNAse P as an endogenous control. Data were analyzed using comparative Ct method and are expressed as 2^−Δct. Placental 8-OHdG is expressed as ng/μg DNA.