Journal article
Analysis of mitochondrial regulatory transcripts in publicly available datasets with validation in placentae from pre-term, post-term and fetal growth restriction pregnancies
Placenta, Vol.112, pp.162-171
2021
PMID: 34364121
Abstract
The human placenta has a defined lifespan and placental aging is a key feature as pregnancy progresses. Placental aging and mitochondrial dysfunction are known to play a key role in pregnancy pathophysiology. Premature aging of the placenta has also been linked with placental dysfunction resulting in poor fetal development and premature birth.
The expression of key mitochondrial-related genes were analysed in a series of publicly available databases then expression changes were validated in placental samples collected from term, pre-term, post-term pregnancies and pregnancies complicated by fetal growth restriction (FGR). Gene and protein expression levels of MFN1, MFN2, TFAM, TOMM20, OPA3 and SIRT4 were measured in placental tissues via qPCR and western blotting.
Initial analysis found that key mitochondrial transcripts related to biogenesis, bioenergetics and mitophagy clustered by pregnancy trimester. A refined list of 13 mitochondrial-related genes were investigated in additional external datasets of pregnancy complications. In the new cohort, protein expression of MFN1 was decreased in FGR and MFN2 is decreased in post-term placenta. Analysis of placental tissues revealed that TOMM20 gene and protein expression was altered in FGR and post-term placenta.
MFN1 and MFN2 play a major role in mitochondrial dynamics, and alterations in these markers have been highlighted in early unexplained miscarriage. TOMM20 is an importer protein that plays a major role in mitophagy and changes have also been identified in age-related diseases. Significant changes in MFN1, MFN2 and TOMM20 indicate that mitochondrial regulators play a critical role in placental aging and placental pathophysiology.
•Mitochondrial-related genes are examined in placentas from publicly available datasets.•Selected mitochondrial-related markers were measured in a separate cohort.•Transcripts involved in biogenesis, bioenergetics and mitophagy cluster by trimester.•MFN1, MFN2 and TOMM20 are dysregulated in FGR and post-term placenta.•Mitophagy and dynamics play an important role in placental pathophysiology.
Details
- Title
- Analysis of mitochondrial regulatory transcripts in publicly available datasets with validation in placentae from pre-term, post-term and fetal growth restriction pregnancies
- Authors
- Lucy A. Bartho (Author) - Griffith UniversityJessica L. O'Callaghan (Author) - Queensland University of TechnologyJoshua J. Fisher (Author) - University of Newcastle AustraliaJames S.M. Cuffe (Author) - University of QueenslandTu'uhevaha J. Kaitu'u-Lino (Author) - University of MelbourneNatalie J. Hannan (Author) - University of MelbourneVicki L. Clifton (Author) - University of QueenslandAnthony V. Perkins (Author) - Griffith University
- Publication details
- Placenta, Vol.112, pp.162-171
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/j.placenta.2021.07.303
- ISSN
- 1532-3102
- PMID
- 34364121
- Organisation Unit
- University of the Sunshine Coast, Queensland; School of Health and Behavioural Sciences - Legacy; School of Health
- Language
- English
- Record Identifier
- 99685296502621
- Output Type
- Journal article
Metrics
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- Collaboration types
- Domestic collaboration
- Web Of Science research areas
- Developmental Biology
- Obstetrics & Gynecology
- Reproductive Biology
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Source: InCites