Therapeutically targeting mitochondrial redox signalling alleviates endothelial dysfunction in preeclampsia

Aberrant placentation generating placental oxidative stress is proposed to play a critical role in the pathophysiology of preeclampsia. Unfortunately, therapeutic trials of antioxidants have been uniformly disappointing. There is provisional evidence implicating mitochondrial dysfunction as a source of oxidative stress in preeclampsia. Here we provide evidence that mitochondrial reactive oxygen species mediates endothelial dysfunction and establish that directly targeting mitochondrial scavenging may provide a protective role. Human umbilical vein endothelial cells exposed to 3% plasma from women with pregnancies complicated by preeclampsia resulted in a significant decrease in mitochondrial function with a subsequent significant increase in mitochondrial superoxide generation compared to cells exposed to plasma from women with uncomplicated pregnancies. Real-time PCR analysis showed increased expression of inflammatory markers TNF-α, TLR-9 and ICAM-1 respectively in endothelial cells treated with preeclampsia plasma. MitoTempo is a mitochondrial-targeted antioxidant, pre-treatment of cells with MitoTempo protected against hydrogen peroxide-induced cell death. Furthermore MitoTempo significantly reduced mitochondrial superoxide production in cells exposed to preeclampsia plasma by normalising mitochondrial metabolism. MitoTempo significantly altered the inflammatory profile of plasma treated cells. These novel data support a functional role for mitochondrial redox signaling in modulating the pathogenesis of preeclampsia and identifies mitochondrial-targeted antioxidants as potential therapeutic candidates.

Parents' concerns about future pregnancy after stillbirth: a qualitative study

Objectives: As stillbirth has a devastating impact, it is imperative to understand the importance of clinical and emotional care after stillbirth and how it influences subsequent pregnancies. The aim of the study was to gain insight into the consideration and planning of a subsequent pregnancy by parents in the weeks following stillbirth. Design: A qualitative semi-structured interview format was utilized. Interpretative phenomenological analysis was employed as the analytic strategy. Participants and setting: The recruitment strategy focused on couples whereby the parents of ten stillborn babies were contacted; however, five men declined to participate in the study. The final sample of 15 parents were all Irish: ten of whom were female and five of whom were male. Results: Findings revealed two superordinate themes relating to a subsequent pregnancy after stillbirth: aspirations for future pregnancy and expectations of future care. Parents disclosed how the prospect of a subsequent pregnancy was daunting with fears about the potential loss of another child. Despite these fears, parentsâ aspirations differed in the days following stillbirth; mothers wished to plan a future pregnancy while fathers were reluctant to consider any pregnancies. Parents were unsure of what to expect in terms of the level of care that would be provided to them in a subsequent pregnancy. Additional appointments at the maternity hospital were considered crucial to provide reassurance during a subsequent pregnancy. Conclusions: These findings underscore the far-reaching and contrasting effects of stillbirth on parents. These complex needs highlight the importance of the multidisciplinary team approach.Objectives: As stillbirth has a devastating impact, it is imperative to understand the importance of clinical and emotional care after stillbirth and how it influences subsequent pregnancies. The aim of the study was to gain insight into the consideration and planning of a subsequent pregnancy by parents in the weeks following stillbirth. Design: A qualitative semi-structured interview format was utilized. Interpretative phenomenological analysis was employed as the analytic strategy. Participants and setting: The recruitment strategy focused on couples whereby the parents of ten stillborn babies were contacted; however, five men declined to participate in the study. The final sample of 15 parents were all Irish: ten of whom were female and five of whom were male. Results: Findings revealed two superordinate themes relating to a subsequent pregnancy after stillbirth: aspirations for future pregnancy and expectations of future care. Parents disclosed how the prospect of a subsequent pregnancy was daunting with fears about the potential loss of another child. Despite these fears, parentsâ aspirations differed in the days following stillbirth; mothers wished to plan a future pregnancy while fathers were reluctant to consider any pregnancies. Parents were unsure of what to expect in terms of the level of care that would be provided to them in a subsequent pregnancy. Additional appointments at the maternity hospital were considered crucial to provide reassurance during a subsequent pregnancy. Conclusions: These findings underscore the far-reaching and contrasting effects of stillbirth on parents. These complex needs highlight the importance of the multidisciplinary team approach.