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Maternal and Fetal Mitochondrial Gene Dysregulation in Hypertensive Disorders of Pregnancy
Journal article   Open access   Peer reviewed

Maternal and Fetal Mitochondrial Gene Dysregulation in Hypertensive Disorders of Pregnancy

Contessa A. Ricci, Danielle M. Reid, Jie Sun, Donna A. Santillan, Mark K. Santillan, Nicole R. Phillips and Styliani Goulopoulou
Physiological genomics, Vol.55(7), pp.275-285
07/2023
DOI: 10.1152/physiolgenomics.00005.2023
PMCID: PMC10292966
PMID: 37184228
url
https://doi.org/10.1152/physiolgenomics.00005.2023View
Published (Version of record) Open Access

Abstract

Mitochondrial 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) were conducted in publicly available high throughput sequencing transcriptomic datasets. 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, while 9 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, while 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.

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