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Endocytosis in the placenta: an undervalued mediator of placental transfer

Endocytosis in the placenta: an undervalued mediator of placental transfer
Endocytosis in the placenta: an undervalued mediator of placental transfer

Endocytosis is an essential mechanism for cellular uptake in many human tissues. A range of endocytic mechanisms occur including clathrin-dependent and -independent mechanisms. However, the role of endocytosis in the placenta and the spatial localisation of individual mechanisms is not well understood. The two principal cell layers that comprise the placental barrier to maternal-fetal transfer are the syncytiotrophoblast and fetal capillary endothelium. Endocytic uptake into the syncytiotrophoblast has been demonstrated for physiological maternal molecules such as transferrin-bound iron and low density lipoprotein (LDL) and may play an important role in the uptake of several other micronutrients, serum proteins, and therapeutics at both major placental cell barriers. These mechanisms may also mediate placental uptake of some viruses and nanoparticles. This review introduces the mechanisms of cargo-specific endocytosis and what is known about their localisation in the placenta, focussing predominantly on the syncytiotrophoblast. A fuller understanding of placental endocytosis is necessary to explain both fetal nutrition and the properties of the placental barrier. Characterising placental endocytic mechanisms and their regulation may allow us to identify their role in pregnancy pathologies and provide new avenues for therapeutic intervention.

Albumin, Caveolin, Clathrin, Syncytiotrophoblast, TfR1, hFcRn
0143-4004
67-73
Cooke, Laura D F
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Tumbarello, David A
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Harvey, Nicholas C
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Sethi, Jaswinder K
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Lewis, Rohan M
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Cleal, Jane K
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Cooke, Laura D F
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Tumbarello, David A
75c6932e-fdbf-4d3c-bb4f-48fbbdba93a2
Harvey, Nicholas C
ce487fb4-d360-4aac-9d17-9466d6cba145
Sethi, Jaswinder K
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Lewis, Rohan M
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Cleal, Jane K
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Cooke, Laura D F, Tumbarello, David A, Harvey, Nicholas C, Sethi, Jaswinder K, Lewis, Rohan M and Cleal, Jane K (2021) Endocytosis in the placenta: an undervalued mediator of placental transfer. Placenta, 113, 67-73. (doi:10.1016/j.placenta.2021.04.014).

Record type: Article

Abstract

Endocytosis is an essential mechanism for cellular uptake in many human tissues. A range of endocytic mechanisms occur including clathrin-dependent and -independent mechanisms. However, the role of endocytosis in the placenta and the spatial localisation of individual mechanisms is not well understood. The two principal cell layers that comprise the placental barrier to maternal-fetal transfer are the syncytiotrophoblast and fetal capillary endothelium. Endocytic uptake into the syncytiotrophoblast has been demonstrated for physiological maternal molecules such as transferrin-bound iron and low density lipoprotein (LDL) and may play an important role in the uptake of several other micronutrients, serum proteins, and therapeutics at both major placental cell barriers. These mechanisms may also mediate placental uptake of some viruses and nanoparticles. This review introduces the mechanisms of cargo-specific endocytosis and what is known about their localisation in the placenta, focussing predominantly on the syncytiotrophoblast. A fuller understanding of placental endocytosis is necessary to explain both fetal nutrition and the properties of the placental barrier. Characterising placental endocytic mechanisms and their regulation may allow us to identify their role in pregnancy pathologies and provide new avenues for therapeutic intervention.

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Accepted_Manuscript_Endocytosis_in_the_placenta - Accepted Manuscript
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Accepted/In Press date: 27 April 2021
e-pub ahead of print date: 3 May 2021
Published date: 3 May 2021
Additional Information: Funding Information: LDFC is funded by the Gerald Kerkut Charitable Trust ; DAT is funded by the Wellcome Trust Seed Award ( 205909/Z/17/Z ); NCH is funded by the MRC , NIHR , Versus Athritis , BBSRC , and Wellcome Trust ; JKS is funded by the Wellcome Trust (Grant Number 206453/Z/17/Z ); RML and JKC are supported by BBSRC ( BB/R002762/1 ) and Wellbeing of Women ; RML is also funded by The Leverhulme Trust . Publisher Copyright: © 2021 Elsevier Ltd Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
Keywords: Albumin, Caveolin, Clathrin, Syncytiotrophoblast, TfR1, hFcRn

Identifiers

Local EPrints ID: 449571
URI: http://eprints.soton.ac.uk/id/eprint/449571
ISSN: 0143-4004
PURE UUID: 30e51285-b703-4545-bb29-db95d199e663
ORCID for David A Tumbarello: ORCID iD orcid.org/0000-0002-5169-0561
ORCID for Nicholas C Harvey: ORCID iD orcid.org/0000-0002-8194-2512
ORCID for Jaswinder K Sethi: ORCID iD orcid.org/0000-0003-4157-0475
ORCID for Rohan M Lewis: ORCID iD orcid.org/0000-0003-4044-9104
ORCID for Jane K Cleal: ORCID iD orcid.org/0000-0001-7978-4327

Catalogue record

Date deposited: 08 Jun 2021 16:31
Last modified: 26 Nov 2021 03:11

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Contributors

Author: Laura D F Cooke
Author: Rohan M Lewis ORCID iD
Author: Jane K Cleal ORCID iD

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