dc.contributor.author |
Zhao, Mingzhi |
en |
dc.contributor.author |
Li, Yanyun |
en |
dc.contributor.author |
Xu, Lance |
en |
dc.contributor.author |
Hickey, Anthony |
en |
dc.contributor.author |
Allan, Katie |
en |
dc.contributor.author |
Stone, Peter |
en |
dc.contributor.author |
Chamley, Lawrence |
en |
dc.contributor.author |
Chen, Qi |
en |
dc.date.accessioned |
2018-10-16T21:18:48Z |
en |
dc.date.issued |
2017-10 |
en |
dc.identifier.issn |
0143-4004 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/42069 |
en |
dc.description.abstract |
The exact cause of preeclampsia is unknown. However a "toxin" from the placenta triggers the condition via activation of the maternal endothelium. Extracellular vesicles (EVs) from the syncytiotrophoblast, may be an endothelial-activating toxin. Antiphospholipid antibodies (aPL) and preeclamptic sera both induce the production of endothelial cell-activating EVs by mechanisms which may produce excess free-radicals in the placenta. Melatonin is produced by the human placenta and has both direct and indirect anti-free-radical properties and may therefore counter the effects of aPL and preeclamptic sera.First trimester placental explants were exposed to preeclamptic sera or aPL in the presence or absence of melatonin. Nitrosylative damage was assessed in the explants by immunohistochemistry and the effect of EVs from these explants on endothelial cell activation determined by ICAM-1. Release of nitrosylated proteins from the explants was also measured.Placental explants showed reduced secretion of melatonin after treatment with preeclamptic sera. Nitrosylated proteins were more abundant in placentae that had been treated with aPL or preeclamptic sera and EVs from such placentae induced endothelial cell activation. Adding melatonin to the aPL or preeclamptic sera reversed the protein nitrosylation and production of endothelial-activating EVs.Our data are consistent with reports that the levels of circulating melatonin are reduced in preeclampsia and suggest that aPL and factors in preeclamptic sera induce free-radical-mediated damage in the placenta leading to the production of endothelial-activating EVs. Melatonin reversing production of endothelial-activating EVs indicates that melatonin may have therapeutic benefits in women with preeclampsia and/or aPL. |
en |
dc.format.medium |
Print-Electronic |
en |
dc.language |
eng |
en |
dc.relation.ispartofseries |
Placenta |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.subject |
Endothelial Cells |
en |
dc.subject |
Trophoblasts |
en |
dc.subject |
Placenta |
en |
dc.subject |
Humans |
en |
dc.subject |
Pre-Eclampsia |
en |
dc.subject |
Reactive Nitrogen Species |
en |
dc.subject |
Melatonin |
en |
dc.subject |
Antibodies, Antiphospholipid |
en |
dc.subject |
Pregnancy |
en |
dc.subject |
Pregnancy Trimester, First |
en |
dc.subject |
Adult |
en |
dc.subject |
Female |
en |
dc.subject |
Young Adult |
en |
dc.subject |
Extracellular Vesicles |
en |
dc.title |
Melatonin prevents preeclamptic sera and antiphospholipid antibodies inducing the production of reactive nitrogen species and extrusion of toxic trophoblastic debris from first trimester placentae. |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1016/j.placenta.2017.08.001 |
en |
pubs.begin-page |
17 |
en |
pubs.volume |
58 |
en |
dc.rights.holder |
Copyright: The author |
en |
dc.identifier.pmid |
28962691 |
en |
pubs.end-page |
24 |
en |
pubs.publication-status |
Published |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Journal Article |
en |
pubs.elements-id |
650241 |
en |
pubs.org-id |
Liggins Institute |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
School of Medicine |
en |
pubs.org-id |
Obstetrics and Gynaecology |
en |
pubs.org-id |
Science |
en |
pubs.org-id |
Biological Sciences |
en |
pubs.org-id |
Science Research |
en |
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
en |
dc.identifier.eissn |
1532-3102 |
en |
pubs.record-created-at-source-date |
2017-10-01 |
en |
pubs.dimensions-id |
28962691 |
en |