Karolczak-Bayatti, M, Forbes, K orcid.org/0000-0002-3745-1337, Horn, J et al. (4 more authors) (2019) IGF signalling and endocytosis in the human villous placenta in early pregnancy as revealed by comparing quantum dot conjugates with a soluble ligand. Nanoscale, 11 (25). pp. 12285-12295. ISSN 2040-3364
Abstract
A complex combination of trafficking and signalling occurs at the surface of the placenta. The system delivers maternal nutrients to the fetus and facilitates gaseous exchange, whilst mediating signal transduction to support and stimulate the growth of the placenta itself. IGF-I is acknowledged as a maternally-derived ligand important in the regulation of placental growth. Here we show that quantum dots bearing IGF can stimulate IGF receptor (IGF1R) phosphorylation in the syncytio- (maternal-facing) and cyto- (fetal-facing) trophoblast bilayer that forms the outer boundary of the placenta, in a distribution similar to the one resulting from exposure to a soluble ligand. The conjugates are internalised by a clathrin-dependent pathway and delivered to a syncytioplasmic compartment that differs from conventional late endosomes and lysosomes. Two discrete downstream responses are evident in different cellular compartments: phosphorylation of P70S6K in the non-proliferative syncytiotrophoblast and of AKT in the cytotrophoblast. Co-conjugation of IGF-quantum dots with an RGD-containing ligand permits penetration beyond the syncytium, into the cytoplasm of the underlying cytotrophoblast. These data reveal the existence of a trans-syncytial pathway that allows maternal mitotic signals to penetrate to the inner progenitor cells, which must proliferate to support placental and consequently fetal growth.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Royal Society of Chemistry 2019. This article is protected by copyright. This is an author produced version of a paper published in Nanoscale. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | IGF; placenta |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 18 Jun 2019 10:50 |
Last Modified: | 06 Jun 2020 00:38 |
Published Version: | https://pubs.rsc.org/en/content/articlelanding/201... |
Status: | Published |
Publisher: | Royal Society of Chemistry |
Identification Number: | 10.1039/C8NR10337B |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:147471 |