Maternal and fetal mitochondrial gene dysregulation in hypertensive disorders of pregnancy

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dc.creatorRicci, Contessa A.
dc.creatorReid, Danielle M.
dc.creatorSun, Jie
dc.creatorSantillan, Donna A.
dc.creatorSantillan, Mark K.
dc.creatorPhillips, Nicole R.
dc.creatorGoulopoulou, Styliani
dc.creator.orcid0000-0002-9324-2687 (Phillips, Nicole R.)
dc.date.accessioned2023-07-12T13:34:23Z
dc.date.available2023-07-12T13:34:23Z
dc.date.issued2023-05-15
dc.description.abstractMitochondrial dysfunction has been implicated in pregnancy-induced hypertension (PIH). The role of mitochondrial gene dysregulation in PIH, and consequences for maternal-fetal interactions, remain elusive. Here, we investigated mitochondrial gene expression and dysregulation in maternal and placental tissues from pregnancies with and without PIH; further, we measured circulating mitochondrial DNA (mtDNA) mutational load, an index of mtDNA integrity. Differential gene expression analysis followed by Time Course Gene Set Analysis (TcGSA) was conducted on publicly available high throughput sequencing transcriptomic data sets. Mutational load analysis was carried out on peripheral mononuclear blood cells from healthy pregnant individuals and individuals with preeclampsia. Thirty mitochondrial differentially expressed genes (mtDEGs) were detected in the maternal cell-free circulating transcriptome, whereas nine were detected in placental transcriptome from pregnancies with PIH. In PIH pregnancies, maternal mitochondrial dysregulation was associated with pathways involved in inflammation, cell death/survival, and placental development, whereas fetal mitochondrial dysregulation was associated with increased production of extracellular vesicles (EVs) at term. Mothers with preeclampsia did not exhibit a significantly different degree of mtDNA mutational load. Our findings support the involvement of maternal mitochondrial dysregulation in the pathophysiology of PIH and suggest that mitochondria may mediate maternal-fetal interactions during healthy pregnancy.NEW & NOTEWORTHY This study identifies aberrant maternal and fetal expression of mitochondrial genes in pregnancies with gestational hypertension and preeclampsia. Mitochondrial gene dysregulation may be a common etiological factor contributing to the development of de novo hypertension in pregnancy-associated hypertensive disorders.
dc.description.sponsorshipThis research was supported in part by the National Institutes of Health (R01HL0146562; R01HL146562-04S1; R01HD089940), National Institutes on Minority Health and Health Disparities of the National Institutes of Health (U54MD006882), American Heart Association (18SCG34350001, 15SFRN 23730000, 15SFRN 23480000), the University of Iowa Carver College of Medicine, and the National Center for Advancing Translational Sciences of the National Institutes of Health (UL1TR002537, UL1TR002537-S1).
dc.identifier.citationRicci, C. A., Reid, D. M., Sun, J., Santillan, D. A., Santillan, M. K., Phillips, N. R., & Goulopoulou, S. (2023). Maternal and fetal mitochondrial gene dysregulation in hypertensive disorders of pregnancy. Physiological genomics, 55(7), 275-285. https://doi.org/10.1152/physiolgenomics.00005.2023
dc.identifier.issn1531-2267
dc.identifier.issue7
dc.identifier.urihttps://hdl.handle.net/20.500.12503/32372
dc.identifier.volume55
dc.publisherAmerican Physiological Society
dc.relation.urihttps://doi.org/10.1152/physiolgenomics.00005.2023
dc.rights.holder© 2023 The Authors.
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourcePhysiological Genomics
dc.subjecthypertension
dc.subjectmitochondrial DNA
dc.subjectpreeclampsia
dc.subjectplacenta
dc.subject.meshPregnancy
dc.subject.meshFemale
dc.subject.meshHumans
dc.subject.meshHypertension, Pregnancy-Induced / genetics
dc.subject.meshPlacenta
dc.subject.meshPre-Eclampsia / genetics
dc.subject.meshGenes, Mitochondrial / genetics
dc.subject.meshDNA, Mitochondrial / genetics
dc.titleMaternal and fetal mitochondrial gene dysregulation in hypertensive disorders of pregnancy
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dc.type.materialArticle

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