McMaster 2018 Am J Obstet Gynecol
|Preeclampsia is associated with placental mitochondrial dysfunction.|
Event: Am J Obstet Gynecol
We have demonstrated that serum from women with preeclampsia (PE) contains circulating factors which contribute to mitochondrial (Mt) dysfunction and increased reactive oxygen species in cultured human vascular endothelial cells. When Mt are damaged or dysfunctional, there is an increase in mtDNA copy number, with an associated decreased Electron Transport Chain (ETC) expression, activity and respiration. The objective of this study is to determine if Mt isolated from placentas of women with PE exhibit more of these features compared to Mt from normotensive pregnant (NP) women.
Intact placental Mt were isolated from of NP and PE women, real-time PCR was used to determine the relative quantity of mtDNA compared to nuclear DNA, and complex expression was determined by Western blot with OxPhos, an antibody cocktail targeting the 5 ETC complexes. Finally ETC complex IV activities and respiration rates were measured using Oxygraph-2K. Respiration rates measured include: basal state (no substrates), state 2 (glutamate/malate), state 3 (ADP), state 4 (oligomycin), and maximal state (FCCP).
There is significantly increased placental mtDNA in PE vs NP (159 ±25, n=3 vs 78.04±10, n=3, p=0.042). We noted a trend toward decreased expression of Complex I and II. Complex IV expression is significantly decreased in PE vs NP (0.505±0.09, n=3 vs. 0.912±0.08, n=3 Complex IV/VDAC, p=0.029). Additionally, complex IV activity was drastically reduced in PE vs NP (141.4±18, n=9 vs 238.5±24, n=10 nmol e-/min/mg, P<0.01). In our preliminary data (n=2), we noted a downward trend in Complex I mediated State 3 and maximal state respiration rates in PE.
In preeclampsia, there is significantly increased placental Mt DNA mean copy numbers and a simultaneous decrease in ETC Complex IV expression and activity. Impairment of mitochondrial respiration and ETC activities in PE indicate that mitochondrial dysfunction could contribute to oxidative stress and other pathophysiological features of preeclampsia.
• Bioblast editor: Kandolf G
Labels: MiParea: Respiration, mtDNA;mt-genetics, nDNA;cell genetics
Preparation: Isolated mitochondria
Coupling state: LEAK, ROUTINE, OXPHOS, ET Pathway: N HRR: Oxygraph-2k
- Univ Mississippi Medical Center, Jackson, MS, USA.