Proteomic Analysis of Placental Mitochondria Following Trophoblast Differentiation

Fisher, Joshua J.; McKeating, Daniel R.; Cuffe, James; Bianco‐Miotto, Tina; Holland, Olivia J.; Perkins, Anthony V.

doi:10.3389/fphys.2019.01536

Cited by 26 publications

(27 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…No significant differences were found with GDM; however, the findings did validate the previous observations with all proteins significantly decreased in Syncytio‐Mito when compared with Cyto‐Mito, regardless of pathology (Fisher et al . 2019 c ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Mitochondrial dysfunction in placental trophoblast cells experiencing gestational diabetes mellitus

Fisher

Vanderpeet

Bartho

et al. 2020

The Journal of Physiology

Self Cite

View full text Add to dashboard Cite

Key points Mitochondrial dysfunction is known to occur in diabetic phenotypes including type 1 and 2 diabetes mellitus. The incidence of gestational diabetes mellitus (GDM) is increasing and defined as the onset of a diabetic phenotype during pregnancy. The role of placental mitochondria in the aetiology of GDM remains unclear and is an emerging area of research. Differing mitochondrial morphologies within the placenta may influence the pathogenesis of the disorder. This study observed mitochondrial dysfunction in GDM placenta when assessing whole tissue. Upon further investigation into mitochondrial isolates from the cytotrophoblast and syncytiotrophoblast, mitochondrial dysfunction appears exaggerated in syncytiotrophoblast. Assessing mitochondrial populations individually enabled the determination of differences between cell lineages of the placenta and established varying levels of mitochondrial dysfunction in GDM, in some instances establishing significance in pathways previously inconclusive or confounded when assessing whole tissue. This research lays the foundation for future work into mitochondrial dysfunction in the placenta and the role it may play in the aetiology of GDM. Abstract Mitochondrial dysfunction has been associated with diabetic phenotypes, yet the involvement of placental mitochondria in gestational diabetes mellitus (GDM) remains inconclusive. This is in part complicated by the different mitochondrial subpopulations present in the two major trophoblast cell lineages of the placenta. To better elucidate the role of mitochondria in this pathology, this study examined key aspects of mitochondrial function in placentas from healthy pregnancies and those complicated by GDM in both whole tissue and isolated mitochondria. Mitochondrial content, citrate synthase activity, reactive oxygen species production and gene expression regulating metabolic, hormonal and antioxidant control was examined in placental tissue, before examining functional differences between mitochondrial isolates from cytotrophoblast (Cyto‐Mito) and syncytiotrophoblast (Syncytio‐Mito). Our study observed evidence of mitochondrial dysfunction across multiple pathways when assessing whole placental tissue from GDM pregnancies compared with healthy controls. Furthermore, by examining isolated mitochondria from the cytotrophoblast and syncytiotrophoblast cell lineages of the placenta we established that although both mitochondrial populations were dysfunctional, they were differentially impacted. These data highlight the need to consider changes in mitochondrial subpopulations at the feto‐maternal interface when studying pregnancy pathologies.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Mitochondria from the syncytiotrophoblasts have decreased rates of respiration, adenosine triphosphate (ATP) generation and alterations in expression of mitochondrial complex proteins ATP5α, ATP5β, as well as a decrease in a number of metabolic pathways (Fisher et al . 2019 a , c ).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial dysfunction in placental trophoblast cells experiencing gestational diabetes mellitus

Fisher

Vanderpeet

Bartho

et al. 2020

The Journal of Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…PE is a vascular disease that occurs during pregnancy and results in the impairment of placental development [21]. The differentiation of trophoblasts in the placenta could form the multinuclear layer-covering placenta, playing an essential role in the etiology of PE [22]. The current study was conducted with the main objective of determining the mechanism by which miR-101 encapsulated in EV released from HUCMSCs affects proliferation and migration of trophoblasts in vitro and the blood pressure and urine protein in a rat model of PE in vivo.…”

Section: Discussionmentioning

confidence: 99%

MiR-101-containing extracellular vesicles bind to BRD4 and enhance proliferation and migration of trophoblasts in preeclampsia

et al. 2020

View full text Add to dashboard Cite

Background: Preeclampsia (PE) is a frequently occurring pregnancy disorder in the placenta, which results in various maternal and fetal complications. The current study aims to evaluate the role of extracellular vesicles (EVs)encapsulated microRNA (miR)-101 in biological processes of trophoblasts in PE and its underlying mechanism. Methods: Human umbilical cord mesenchymal stem cell (HUCMSC) and HUCMSC-derived EVs were isolated and cultured, after which EV characterization was carried out using PKH67 staining. In silico analyses were adopted to predict the downstream target genes of miR-101, and dual luciferase reporter gene assay was applied to validate the binding affinity. Furthermore, loss-and gain-of-function approaches were adopted to determine the role of miR-101 and bromodomain-containing protein 4 (BRD4) in trophoblast proliferation and invasion using EDU staining and transwell assay. In addition, a rat model of PE was established to verify the function of EV-encapsulated miR-101 in vivo. Results: Placental tissues obtained from PE patients presented with downregulated miR-101 expression and upregulated BRD4 and CXCL11 expression. EV-encapsulated miR-101 from HUCMSCs could be delivered into the trophoblast HTR-8/SVneo cells, thus enhancing proliferation and migration of trophoblasts. Mechanically, miR-101 targeted and negatively regulated BRD4 expression. BRD4 knockdown promoted the proliferation and migration of trophoblasts by suppressing NF-κB/CXCL11 axis. EV-encapsulated miR-101 from HUCMSCs also reduced blood pressure and 24 h urine protein in vivo, thereby ameliorating PE. Conclusion: In summary, EV-encapsulated miR-101 promoted proliferation and migration of placental trophoblasts through the inhibition of BRD4 expression via NF-κB/CXCL11 inactivation.

show abstract

“…Out of these 340 proteins, 208 were not previously detected in the studies conducted by Paradela et al (2005) or Zhang et al (2010), emphasizing the variability of this approach based on tissue sampling, extraction approaches, and analyses (Vandré et al, 2012). Fisher et al (2019) used sequential centrifugation to enrich mitochondrial fractions based on the distinct structural differences apparent between mitochondria in CTBs (larger mitochondria with defined cristae) and STB (smaller and punctate mitochondria with diffuse cristae). LC-MS/MS was then performed to evaluate proteomic differences between STB and CTB mitochondria.…”

Section: Using Omics To Define the Stb Metabolome And Sub-proteomementioning

confidence: 99%

Omics Approaches to Study Formation and Function of Human Placental Syncytiotrophoblast

Jaremek

Jeyarajah

Bhattad

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Proper development of the placenta is vital for pregnancy success. The placenta regulates exchange of nutrients and gases between maternal and fetal blood and produces hormones essential to maintain pregnancy. The placental cell lineage primarily responsible for performing these functions is a multinucleated entity called syncytiotrophoblast. Syncytiotrophoblast is continuously replenished throughout pregnancy by fusion of underlying progenitor cells called cytotrophoblasts. Dysregulated syncytiotrophoblast formation disrupts the integrity of the placental exchange surface, which can be detrimental to maternal and fetal health. Moreover, various factors produced by syncytiotrophoblast enter into maternal circulation, where they profoundly impact maternal physiology and are promising diagnostic indicators of pregnancy health. Despite the multifunctional importance of syncytiotrophoblast for pregnancy success, there is still much to learn about how its formation is regulated in normal and diseased states. ‘Omics’ approaches are gaining traction in many fields to provide a more holistic perspective of cell, tissue, and organ function. Herein, we review human syncytiotrophoblast development and current model systems used for its study, discuss how ‘omics’ strategies have been used to provide multidimensional insights into its formation and function, and highlight limitations of current platforms as well as consider future avenues for exploration.

show abstract

Proteomic Analysis of Placental Mitochondria Following Trophoblast Differentiation

Cited by 26 publications

References 19 publications

Mitochondrial dysfunction in placental trophoblast cells experiencing gestational diabetes mellitus

Mitochondrial dysfunction in placental trophoblast cells experiencing gestational diabetes mellitus

MiR-101-containing extracellular vesicles bind to BRD4 and enhance proliferation and migration of trophoblasts in preeclampsia

Omics Approaches to Study Formation and Function of Human Placental Syncytiotrophoblast

Contact Info

Product

Resources

About