The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

Dealing with the stress of preeclampsia through placental mitochondrial adaptations (#349)

Olivia J Holland 1 , James SM Cuffe 1 2 , Marloes Dekker Nitert 3 4 , Leonie Callaway 3 5 , Keith Kwan Cheung 1 , Filip Radenkovic 1 , Tony V Perkins 1
  1. Griffith University, Gold Coast, QLD, Australia
  2. School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland, Australia
  3. University of Queensland Centre for Clinical Research, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia
  4. School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland, Australia
  5. Women and Newborns, Royal Brisbane and Women’s Hospital, Herston, Queensland, Australia

Preeclampsia is a devastating pregnancy disorder that can quickly and unpredictably become dangerous for both mother and fetus. Severity varies widely, and while severe preeclampsia often requires preterm delivery, women with mild preeclampsia may reach term with minor interventions. The mechanisms that mediate disease severity are poorly understood, but may include adaptive processes by the placenta. We aimed to establish whether placental response to preeclampsia was different in pregnancies that reached term versus those that delivered preterm, and explore potential adaptive mechanisms.

This study included placentae collected from 16 patients with preeclampsia (term delivery n=10, preterm delivery n=6) and 16 control pregnancies (term delivery n=10, preterm delivery n=6). Markers of oxidative stress, antioxidant, mitochondrial, and apoptosis function were analysed.

Hydrogen peroxide production (p=0.003, 1.15 fold) and antioxidant activity (p=0.016, 1.13 fold) were increased in term preeclamptic placentae, whereas preterm preeclamptic placentae had reduced function of the antioxidant superoxide dismutase (activity p=0.029, 0.79 fold). Mitochondrial fusion (L-OPA1/S-OPA1 p=0.0007, 1.62 fold; MFN1 p=0.011, 1.78 fold) and anti-apoptosis (BCL2 p=0.016, 1.53 fold) proteins were increased in term preeclamptic placentae. Mitochondrial respiration (mitochondrial complex I, p=0.008, 1.19 fold) and mitochondrial content (p=0.009, 1.46 fold) were increased in term preeclamptic placentae, but mitochondria had a lower respiratory reserve capacity (p=0.001, 0.46 fold).

Placentae from preeclamptic pregnancies that reached term showed multiple mitochondrial-related adaptions that were not present in preterm preeclamptic placentae. Increased antioxidant activity, and expression of markers of mitochondrial fusion and apoptotic suppression, may relate to salvaging damaged mitochondria. Increased mitochondrial content may be the reason for increased respiration, allowing ongoing tissue function even with reduced respiratory efficiency in term preeclamptic pregnancies. Reactive oxygen species signalling in term preeclamptic placentae may be at a level to trigger compensatory antioxidant and mitochondrial responses, allowing tissue level maintenance of function when there is organelle level dysfunction.