Stroke in Pregnancy Brings Epigenetic Changes in Correlation with Affected Mitochondrial Dynamics and Inflammasome Mediated Apoptosis in Rodents.

BACKGROUND: Pregnancy may be a risk factor for stroke in females. Stroke in pregnancy influences mitochondrial dynamics as well as the inflammatory responses in mothers. However, limited studies are available that report any epigenetic changes in the offspring following a stroke in mothers. In the present study we investigate the effect of stroke in pregnancy as a possible epigenetic modifier correlated with dysfunctional mitochondrial dynamics and exacerbated inflammasome mediated apoptosis in the offsprings. METHODS AND RESULTS: Female and male Sprague Dawley rats were housed in the same cage in 1:2 ratio to ensure successful pregnancy. Stroke was induced by middle cerebral artery occlusion at gestational day 17. After delivery of F1 generation, bloods were collected from the dams for hormonal study. Brains were harvested from both dams and F1 generation for biochemical, histological, genetic, molecular, and mitochondrial studies. In the F1 generation of stroke induced dams, an increased mitochondrial fission and decreased mitochondrial fusion were observed as compared with normal dams and their F1 generation. Similarly, enhanced mitochondrial reactive oxygen species and depolarization were also observed in the F1 generation of stroke induced dams. Exacerbated inflammasome signaling and enhanced apoptosis were also evident in this F1 generation. Changes in histone-methylation corresponding to increased inflammation were also observed in this F1 generation. CONCLUSIONS: The present study reports the occurrence of epigenetic modifications towards mitochondrial dysfunction and exacerbated inflammasome mediated apoptosis in the F1 generation following a stroke in pregnant dams.