Susceptibility of human placental syncytiotrophoblastic mitochondria to oxygen-mediated damage in relation to gestational age

Abstract

When maintaining first trimester placental villi in organ culture under conventional normoxic conditions, we have observed widespread degeneration of the syncytiotrophoblast within 24 h despite excellent viability for the cytotrophoblastic and stromal cell types. Here we identify loss of mitochondrial activity as an early event in this process. In the light of proposals that the early part of gestation occurs in a low oxygen environment and also reported associations between mitochondrial disruption and oxidative stress, we cultured first trimester villi under low oxygen conditions (2.5%). Mitochondrial superoxide dismutase (MnSOD) localization and activity at different gestational ages were also determined. It was found that syncytiotrophoblastic and mitochondrial morphology improved, and mitochondrial activity was retained for 6 h and more if 8- to 10-week-old tissue was placed into a low oxygen environment immediately after removal from the uterus. The effect of oxygen concentration was less marked when using tissue of 14 weeks or more gestational age, which showed good survival and retention of mitochondrial activity under both low and ambient oxygen conditions. This correlated with our finding that placental MnSOD activity increased significantly between 8 and 14 weeks of gestation. Immunohistochemistry demonstrated that at 11 weeks; MnSOD was localized predominantly within the cytotrophoblast cells, whereas by 16 weeks it was found in the syncytiotrophoblast also. These results indicate an acute sensitivity of first trimester placenta syncytiotrophoblast to oxygen-mediated damage.