Introduction: Preeclampsia is thought to be associated with restricted maternal blood flow to the placenta. Mitochondria consume oxygen to produce energy, and are sensitive to oxygen levels. Here, mitochondrial respiration and markers of cellular function were investigated in preeclamptic placentae.
Methods: Placental tissue was obtained from laboured term pregnancies (n=6 control; n=6 preeclamptic). Tissue was selectively permeabilized to access syncytiotrophoblast mitochondria, and high-resolution respirometry was used to assess respiration. Syncytiotrophoblast- and cytotrophoblasts-enriched mitochondrial fractions were isolated by differential centrifugation. Western blot was used to access levels of B-cell lymphoma 2 (BCL2; anti-apoptotic) and nuclear respiratory factor 1 (NRF1; mitochondrial biogenesis) in whole lysate, and complex IV and heat shock protein 60 (HSP-60) in mitochondrial fractions. ELISA was used to investigate protein carbonyls as a marker of oxidative stress.
Results: In preeclamptic syncytiotrophoblast mitochondria, respiration (non-phosphorylating respiration, and oxidative phosphorylation through complexes I and I+II) was significantly increased (p<0.05), and the reserve respiratory capacity was significantly reduced (mean±SD: 0.20±0.05 control; 0.15±0.05 preeclamptic; p=0.0042). No change was found in levels of BCL2, NRF1, or in the levels of protein carbonyls between whole tissue lysate from preeclamptic and control placentae. Levels of complex IV and HSP-60 were significantly increased (p=0.0079 and 0.0159) in syncytiotrophoblast-enriched mitochondrial fractions from preeclamptic placentae, no difference was observed in cytotrophoblast-enriched mitochondrial fractions between control and preeclamptic placentae.
Conclusions: The higher syncytiotrophoblast mitochondrial respiration seen in preeclamptic pregnancies may represent an adaptation to limited or intermittent blood flow in vivo. Syncytiotrophoblast mitochondria from preeclamptic pregnancies functioned at closer to maximum capacity (reserve respiratory capacity reduced by 5%), indicating potential damage to these mitochondria. Changes in mitochondrial proteins in syncytiotrophoblast-enriched mitochondrial fractions of preeclamptic pregnancies, but not the cytotrophoblast-enriched mitochondrial fractions or whole tissue, suggests the different trophoblast linages are differentially affected.