Discordant HIF1A mRNA levels and oxidative stress in placental shares of monochorionic twins with selective intra-uterine growth restriction

• Investigated the hypoxic-oxidative status of the placenta from MCT with sIUGR.
• Assessed the levels of HIF1A mRNA, MDA, and 8-OHdG in the placenta shares of each MCT.
• More severe hypoxia/oxidative stress was detected in the placenta of MCT with sIUGR.
• Provided evidences for possible involvement of oxidative stress in sIUGR pathogenesis of MCT.

IntroductionOxidative stress is a key factor in the pathogenesis of intra-uterine growth restriction in singleton. However, its role in selective intra-uterine growth restriction (sIUGR) in monochorionic twins (MCT) is still unknown. This study explored the characteristics of oxidative stresses in the placenta shares of MCT and analyzed their possible connections with sIUGR.MethodsThe placental levels of hypoxia inducible factor-1α gene (HIF1A)mRNA, malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHdG) were evaluated in normal MCT (Group A) and sIUGR MCT (Group B). The results were compared between the placental shares of the larger twins (A1/B1) and smaller twins (A2/B2).ResultsPlacental HIF1A mRNA level significantly increased in Group B. Particularly, HIF1A mRNA level was elevated in the placenta share of the growth-restricted fetus (B2) than the co-twin (B1) (P = 0.036). More discordant HIF1A mRNA level was detected in Group B than Group A with larger inter-twin difference (P = 0.021). The levels of MDA and 8-OHdG were significantly higher in B2 than B1 in sIUGR MCT (P < 0.05). Both the inter-twin differences of MDA and 8-OHdG were also significantly larger in Group B (P < 0.05), indicating that discordant oxidative stress existed in the placental shares of sIUGR pregnancies. Finally, MDA concentration was found inversely correlated with neonatal birth weight, in both sIUGR (r = −0.650, P = 0.022) and normal MCT (r = −0.632, P = 0.027) pregnancies.DiscussionThe elevation of HIF1A mRNA, and MDA/8-OHdG levels in placenta shares of sIUGR MCT suggests that oxidative stress may be involved in the pathogenesis of sIUGR.