Antiphospholipid antibodies bind syncytiotrophoblast mitochondria and alter the proteome of extruded syncytial nuclear aggregates.
BACKGROUND
Antiphospholipid antibodies (aPL) are autoantibodies that increase the risk of women developing the hypertensive disorder pre-eclampsia. aPL are internalised by the syncytiotrophoblast and increase extrusion of necrotic multinucleated syncytial nuclear aggregates (SNAs), which may trigger endothelial dysfunction in pre-eclampsia. The mechanisms by which aPL alter death processes in the syncytiotrophoblast leading to extrusion of SNAs are unknown.


METHODS
First trimester human placentae (n = 10) were dissected into explants and cultured either with aPL (50 μg/mL), isotype-matched control antibody (50 μg/mL), or media for 24 h. Harvested SNAs underwent iTRAQ proteomic analysis. Mitochondria in syncytiotrophoblast treated with aPL labelled with FluoroNanogold were visualised using transmission electron microscopy (TEM).


RESULTS
aPL altered the expression of 72 proteins in SNAs. Thirteen proteins were involved in mitochondrial function. TEM demonstrated that aPL bind to mitochondria in the syncytiotrophoblast and may cause mitochondrial swelling.


CONCLUSIONS
aPL disrupt mitochondria increasing the extrusion of SNAs with an altered proteome from the syncytiotrophoblast. These altered SNAs may trigger endothelial dysfunction and pre-eclampsia in these pregnancies.
Department of Obstetrics & Gynaecology, The University of Auckland, Auckland, New Zealand; Department of Pediatrics, Section of Neonatology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. Electronic address: priyadarshini.pantham@ucdenver.edu.
Priyadarshini
P
Pantham
Department of Obstetrics & Gynaecology, The University of Auckland, Auckland, New Zealand.
Chez A
CA
Viall
Department of Obstetrics & Gynaecology, The University of Auckland, Auckland, New Zealand.
Qi
Q
Chen
Centre for Protein Research, University of Otago, Dunedin, New Zealand.
Torsten
T
Kleffmann
Department of Molecular Medicine and Pathology, The University of Auckland, Auckland, New Zealand; Bioinformatics Institute, The University of Auckland, Auckland, New Zealand.
Cristin G
CG
Print
Department of Obstetrics & Gynaecology, The University of Auckland, Auckland, New Zealand.
Lawrence W
LW
Chamley
D017152:Antibodies, Antiphospholipid / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D005260:Female; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D020543:Proteome / Q000378:metabolism*; D014327:Trophoblasts / Q000378:metabolism*
D017152:Antibodies, Antiphospholipid; D020543:Proteome
Apoptosis; Necrosis; Placenta; Preeclampsia; Proteomics; Syncytiotrophoblast