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Mechanisms Regulating Human Trophoblast Fusion

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Cell Fusions

Abstract

In the human placenta, the syncytiotrophoblast is part of the villous trophoblast, which is the epithelial cover of the placental villi floating in maternal blood. The villous trophoblast is composed of two layers, the syncytiotrophoblast in direct contact to maternal blood and the underlying layer of mononucleated cytotrophoblasts. Throughout pregnancy there is continuous fusion of cytotrophoblast with the syncytiotrophoblast to maintain this highly differentiated layer until delivery. This way the syncytiotrophoblast is continuously supplied with cytoplasmic compounds derived from the fusing cytotrophoblasts. The continuous acquisition of fresh cellular components needs to be balanced by a simultaneous release of apoptotic material from the syncytiotrophoblast into the maternal circulation. In the maintenance of the syncytiotrophoblast, fusion is an essential step and was shown to be regulated by multiple factors, such as cytokines, hormones, protein kinases, transcription factors, proteases and membrane proteins. Here we focus on factors that may play roles in the trophoblast fusion process or in the preparation of the cytotrophoblasts to fuse. We will also speculate on pitfalls when studying trophoblast fusion in vitro.

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Abbreviations

1T:

First trimester trophoblasts

2T:

Second trimester trophoblasts

3T:

Third trimester trophoblasts

ADAM:

A disintegrin and metalloprotease

ASCT:

Alanine, serine and cysteine selective transporters

BW:

BeWo cells

CSF:

Colony stimulating factor

CT:

Cytotrophoblast

EGF:

Epidermal growth factor

Env:

Envelope

ERK:

Extracellular signal-regulated kinase

ERV:

Endogenous retrovirus

GCM:

Glial cell missing

GM-CSF:

Granulocyte-macrophage colony-stimulating factor

hCG:

Human chorionic gonadotropin

HERV:

Human endogenous retrovirus

HLA-G:

Human leukocyte antigen G

hPL:

Human placental lactogen

LIF:

Leukemia-inhibitory factor

MAPK:

Mitogen-activated protein kinase

Mash-2:

Mammalian achaete/scute homolog 2

MIC-1:

Macrophage inhibitory cytokine 1

pc:

Post conception

PKA:

Protein kinase A

PP13:

Placental protein 13

PS:

Phosphatidylserine

ST:

Syncytiotrophoblast

TGF:

Transforming growth factor

TNF:

Tumor necrosis factor

VE:

Villous explants

VEGF:

Vascular endothelial growth factor

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Huppertz, B., Gauster, M. (2011). Mechanisms Regulating Human Trophoblast Fusion. In: Larsson, LI. (eds) Cell Fusions. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9772-9_9

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