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Cited by 6Birth, Development, and HealthMitochondrial Function and PathologyPregnancy and preeclampsia studies

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

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Datta, Aishika, Rahane, Dipali, Bhurle, Gangadhar, Akundi, Soumya, Mukherjee, Ushmita, Dubey, Akshada, Barik, Anirban, Karmarkar, Gautam, Malik, Nikita, Ghosh, Bijoyani, Rana, Nikita, Borah, Anupom, Bhattacharya, Pallab·2025·Journal of the American Heart Association
DOI 10.1161/jaha.124.039411PMC PMC12184259
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Abstract

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.

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Figure 1 Effect of stroke in pregnancy on hormonal levels of dams, changes in biochemical parameters, gene expressions and mitochondrial health of F1 generation. A, Graph representing the level of estradiol and progesterone in pregnant rats of different groups (n=3; acknowledgement Jyoti Pathology Diagnostics at Gandhinagar) and (B) graph representing body weight and body length of pups. (C) Graphs of malondialdehyde, nitrite, and reduced glutathione levels in brain of pups of different groups (n=4–6); (D) Graph of mRNA levels of SIRT1 (Sirtuin‐1), OPA1 (optic atrophy 1), FIS1 (mitochondrial fission 1) (n=6); (E) representative images and corresponding graphs of mitochondrial ROS (MitoSox) and mitochondrial membrane potential (JC‐1) (n=4–6); (F) representative graph of percentage respiratory control ratio of pups of different groups (n=5–6). Data are expressed as mean±SD and analyzed for statistical significance using 1‐way Analysis of variance (ANOVA) with Tukey multiple‐comparison test, ***P<0.001, **P<0.01, *P<0.5.
Figure 1 Effect of stroke in pregnancy on hormonal levels of dams, changes in biochemical parameters, gene expressions and mitochondrial health of F1 generation. A, Graph representing the level of estradiol and progesterone in pregnant rats of different groups (n=3; acknowledgement Jyoti Pathology Diagnostics at Gandhinagar) and (B) graph representing body weight and body length of pups. (C) Graphs of malondialdehyde, nitrite, and reduced glutathione levels in brain of pups of different groups (n=4–6); (D) Graph of mRNA levels of SIRT1 (Sirtuin‐1), OPA1 (optic atrophy 1), FIS1 (mitochondrial fission 1) (n=6); (E) representative images and corresponding graphs of mitochondrial ROS (MitoSox) and mitochondrial membrane potential (JC‐1) (n=4–6); (F) representative graph of percentage respiratory control ratio of pups of different groups (n=5–6). Data are expressed as mean±SD and analyzed for statistical significance using 1‐way Analysis of variance (ANOVA) with Tukey multiple‐comparison test, ***P<0.001, **P<0.01, *P<0.5.CC BY-NC-ND · PubMed Central
Figure 2 Effect of stroke in pregnancy on mitochondrial proteins and histone lysine methylation of F1 generation. A, Representative immunoblots and their corresponding graphs of DRP1 (dynamin‐related protein 1), FIS1 (mitochondrial fission 1), OPA1 (optic atrophy 1), MFN1 (mitofusin‐1), MFN2 (mitofusin‐2), TFAM (mitochondrial transcription factor A), PGC1α (proliferator‐activated receptor gamma coactivator 1 α), H3K4Me3 (histone H3 lysine 4 trimethylation), H3K27Me2 (histone H3 dimethyl Lys27) and H3K79Me (histone H3 methylated at lysine 79) (n=6). Data are expressed as mean±SD and analyzed for statistical significance using 1‐way ANOVA with Tukey multiple‐comparison test, ***P<0.001, **P<0.01, *P<0.5.
Figure 2 Effect of stroke in pregnancy on mitochondrial proteins and histone lysine methylation of F1 generation. A, Representative immunoblots and their corresponding graphs of DRP1 (dynamin‐related protein 1), FIS1 (mitochondrial fission 1), OPA1 (optic atrophy 1), MFN1 (mitofusin‐1), MFN2 (mitofusin‐2), TFAM (mitochondrial transcription factor A), PGC1α (proliferator‐activated receptor gamma coactivator 1 α), H3K4Me3 (histone H3 lysine 4 trimethylation), H3K27Me2 (histone H3 dimethyl Lys27) and H3K79Me (histone H3 methylated at lysine 79) (n=6). Data are expressed as mean±SD and analyzed for statistical significance using 1‐way ANOVA with Tukey multiple‐comparison test, ***P<0.001, **P<0.01, *P<0.5.CC BY-NC-ND · PubMed Central
Figure 3 Effect of stroke in pregnancy on inflammasomes and apoptotic protein expressions of F1 generation. A, Representative immunoblots and their corresponding graphs of interleukin‐1β, ASC1 (apoptosis‐associated speck‐like protein containing a caspase recruitment domain‐1), NLRP 3, NLRP 1 (nucleotide‐binding domain and leucine‐rich repeat containing proteins), Caspase3, Caspase1, BAX (Bcl‐2 Associated X‐protein), and cytochrome C (n=6). Data are expressed as mean±SD and analyzed for statistical significance using 1‐way ANOVA with Tukey multiple‐comparison test, ***P<0.001, **P<0.01, *P<0.5.
Figure 3 Effect of stroke in pregnancy on inflammasomes and apoptotic protein expressions of F1 generation. A, Representative immunoblots and their corresponding graphs of interleukin‐1β, ASC1 (apoptosis‐associated speck‐like protein containing a caspase recruitment domain‐1), NLRP 3, NLRP 1 (nucleotide‐binding domain and leucine‐rich repeat containing proteins), Caspase3, Caspase1, BAX (Bcl‐2 Associated X‐protein), and cytochrome C (n=6). Data are expressed as mean±SD and analyzed for statistical significance using 1‐way ANOVA with Tukey multiple‐comparison test, ***P<0.001, **P<0.01, *P<0.5.CC BY-NC-ND · PubMed Central

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Metadata

Authors
Datta, A., Rahane, D., Bhurle, G., Akundi, S., Mukherjee, U., Dubey, A., Barik, A., Karmarkar, G., Malik, N., Ghosh, B., Rana, N., Borah, A., & Bhattacharya, P.
Affiliations
  • National Institute of Pharmaceutical Education and Research (IN)
  • Assam University (IN)
Corresponding author
  • Datta, Aishika
  • Rahane, Dipali
  • Bhurle, Gangadhar
  • Bhattacharya, Pallab
ORCID
Venue
Journal of the American Heart Association
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2025-05-06
Volume
14
Issue
9
Pages
e039411-e039411
ISSN
2047-9980 (ISSN-L)
DOI
10.1161/jaha.124.039411
PMC
PMC12184259
OpenAlex
W4410038974
Cited by
6
References
2
Citations by year
2026: 5 · 2025: 1
FWCI
9.13
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Journal of the American Heart Association (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
Keywords
stroke in pregnancy, maternal stroke, epigenetic modifications, mitochondrial dynamics, mitochondrial fission, mitochondrial fusion, mitochondrial dysfunction, inflammasome, apoptosis, histone methylation, middle cerebral artery occlusion, neuroinflammation, reactive oxygen species, mitochondrial depolarization
MeSH terms
Animals, Brain, Disease Models, Animal, Female, Male, Mitochondria, Pregnancy, Pregnancy Complications, Cardiovascular, Rats, Sprague-Dawley, Apoptosis, Reactive Oxygen Species, Infarction, Middle Cerebral Artery, Epigenesis, Genetic, Rats, Inflammasomes, Mitochondrial Dynamics

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CoChat. (2026). Citation check: Stroke in Pregnancy Brings Epigenetic Changes in Correlation with Affected Mitochondrial Dynamics and Inflammasome Mediated Apoptosis in Rodents. https://app.cochat.ai/papers/10.1161/jaha.124.039411
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Datta, A., Rahane, D., Bhurle, G., Akundi, S., Mukherjee, U., Dubey, A., Barik, A., Karmarkar, G., Malik, N., Ghosh, B., Rana, N., Borah, A., & Bhattacharya, P. (2025). Stroke in Pregnancy Brings Epigenetic Changes in Correlation with Affected Mitochondrial Dynamics and Inflammasome Mediated Apoptosis in Rodents. Journal of the American Heart Association. https://doi.org/10.1161/jaha.124.039411