Maternal and fetal mitochondrial gene dysregulation in hypertensive disorders of pregnancy

Date

2023-05-15

Authors

Ricci, Contessa A.
Reid, Danielle M.
Sun, Jie
Santillan, Donna A.
Santillan, Mark K.
Phillips, Nicole R.
Goulopoulou, Styliani

ORCID

0000-0002-9324-2687 (Phillips, Nicole R.)

Journal Title

Journal ISSN

Volume Title

Publisher

American Physiological Society

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) 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.

Description

Citation

Ricci, 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

Rights

© 2023 The Authors.

License

Attribution 4.0 International (CC BY 4.0)