Galectin-8 is expressed by villous and extravillous trophoblast of the human placenta

We studied the distribution of laminin (Ln) α1–α3, β1–β3, and γ1 chains, and of the extradomain-A (EDA) and EDB and the oncofetal epitope of fibronectin (Onc-Fn) in extravillous trophoblastic cells and decidua in the human placenta by immunohistochemistry. We found that the transition from villous to extravillous trophoblast was accompanied by emergence of immunoreactivity for EDA-, EDB-, and Onc-Fn among the cells. Furthermore, whereas the villous trophoblastic basement membrane (BM) contains Ln α1, α2, β1, β2, and γ1 chains, immunoreactivity for Ln α1, β1, and γ1, but not for Ln α2 and β2 chains, was detected in association with extravillous trophoblastic cells. Interestingly, although immunoreactivity for the Ln α1, α2, β1, β2, and γ1 chains was detected in all decidual cell BMs, EDB-Fn and Onc-Fn were detected only in decidua that had been invaded by the trophoblast. In summary, our results describe distinct changes in the distribution of Ln and Fn isoforms during the differentiation of villous trophoblast into extravillous trophoblastic cells. Furthermore, EDB- and Onc-Fn are preferentially found in decidua that has been invaded by the trophoblast, indicating that the deposition of these Fn isoforms reflects a decidual cell response to invasion.

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Expression of HERV-W Env Glycoprotein (syncytin) in the Extravillous Trophoblast of First Trimester Human Placenta

Placenta ◽

10.1016/j.placenta.2004.09.002 ◽

2005 ◽

Vol 26 (7) ◽

pp. 556-562 ◽

Cited By ~ 64

Author(s):

A. Malassiné ◽

K. Handschuh ◽

V. Tsatsaris ◽

P. Gerbaud ◽

V. Cheynet ◽

...

Keyword(s):

Human Placenta ◽

First Trimester ◽

Extravillous Trophoblast ◽

Env Glycoprotein

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Integrating High-Throughput Approaches and in vitro Human Trophoblast Models to Decipher Mechanisms Underlying Early Human Placenta Development

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.673065 ◽

2021 ◽

Vol 9 ◽

Author(s):

Bum-Kyu Lee ◽

Jonghwan Kim

Keyword(s):

High Throughput ◽

Human Placenta ◽

Molecular Mechanisms ◽

Molecular Level ◽

Cell Types ◽

Model Systems ◽

Extravillous Trophoblast ◽

Human Trophoblast ◽

Early Human

The placenta is a temporary but pivotal organ for human pregnancy. It consists of multiple specialized trophoblast cell types originating from the trophectoderm of the blastocyst stage of the embryo. While impaired trophoblast differentiation results in pregnancy disorders affecting both mother and fetus, the molecular mechanisms underlying early human placenta development have been poorly understood, partially due to the limited access to developing human placentas and the lack of suitable human in vitro trophoblast models. Recent success in establishing human trophoblast stem cells and other human in vitro trophoblast models with their differentiation protocols into more specialized cell types, such as syncytiotrophoblast and extravillous trophoblast, has provided a tremendous opportunity to understand early human placenta development. Unfortunately, while high-throughput research methods and omics tools have addressed numerous molecular-level questions in various research fields, these tools have not been widely applied to the above-mentioned human trophoblast models. This review aims to provide an overview of various omics approaches that can be utilized in the study of human in vitro placenta models by exemplifying some important lessons obtained from omics studies of mouse model systems and introducing recently available human in vitro trophoblast model systems. We also highlight some key unknown questions that might be addressed by such techniques. Integrating high-throughput omics approaches and human in vitro model systems will facilitate our understanding of molecular-level regulatory mechanisms underlying early human placenta development as well as placenta-associated complications.

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Spatiotemporal expression of SERPINE2 in the human placenta and its role in extravillous trophoblast migration and invasion

Reproductive Biology and Endocrinology ◽

10.1186/1477-7827-9-106 ◽

2011 ◽

Vol 9 (1) ◽

pp. 106 ◽

Cited By ~ 12

Author(s):

Schu-Rern Chern ◽

Sheng-Hsiang Li ◽

Chien-Ling Chiu ◽

Hsiao-Ho Chang ◽

Chih-Ping Chen ◽

...

Keyword(s):

Human Placenta ◽

Extravillous Trophoblast ◽

Migration And Invasion ◽

Spatiotemporal Expression ◽

Trophoblast Migration

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The term basal plate of the human placenta as a source of functional extravillous trophoblast cells

Reproductive Biology and Endocrinology ◽

10.1186/1477-7827-12-7 ◽

2014 ◽

Vol 12 (1) ◽

pp. 7 ◽

Cited By ~ 14

Author(s):

Alexandre U Borbely ◽

Silvana Sandri ◽

Isabella R Fernandes ◽

Karen M Prado ◽

Elaine C Cardoso ◽

...

Keyword(s):

Human Placenta ◽

Basal Plate ◽

Extravillous Trophoblast ◽

Trophoblast Cells

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Notch1 controls development of the extravillous trophoblast lineage in the human placenta

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1612335113 ◽

2016 ◽

Vol 113 (48) ◽

pp. E7710-E7719 ◽

Cited By ~ 46

Author(s):

Sandra Haider ◽

Gudrun Meinhardt ◽

Leila Saleh ◽

Christian Fiala ◽

Jürgen Pollheimer ◽

...

Keyword(s):

Human Placenta ◽

Extravillous Trophoblast ◽

Trophoblast Differentiation ◽

Successful Pregnancy ◽

Self Renewal ◽

Human Trophoblast ◽

Key Factor ◽

Induced Genes ◽

Exchange Surface ◽

Extravillous Trophoblasts

Development of the human placenta and its different epithelial trophoblasts is crucial for a successful pregnancy. Besides fusing into a multinuclear syncytium, the exchange surface between mother and fetus, progenitors develop into extravillous trophoblasts invading the maternal uterus and its spiral arteries. Migration into these vessels promotes remodelling and, as a consequence, adaption of blood flow to the fetal–placental unit. Defects in remodelling and trophoblast differentiation are associated with severe gestational diseases, such as preeclampsia. However, mechanisms controlling human trophoblast development are largely unknown. Herein, we show that Notch1 is one such critical regulator, programming primary trophoblasts into progenitors of the invasive differentiation pathway. At the 12th wk of gestation, Notch1 is exclusively detected in precursors of the extravillous trophoblast lineage, forming cell columns anchored to the uterine stroma. At the 6th wk, Notch1 is additionally expressed in clusters of villous trophoblasts underlying the syncytium, suggesting that the receptor initiates the invasive differentiation program in distal regions of the developing placental epithelium. Manipulation of Notch1 in primary trophoblast models demonstrated that the receptor promotes proliferation and survival of extravillous trophoblast progenitors. Notch1 intracellular domain induced genes associated with stemness of cell columns, myc and VE-cadherin, in Notch1−fusogenic precursors, and bound to themycpromoter and enhancer region at RBPJκ cognate sequences. In contrast, Notch1 repressed syncytialization and expression of TEAD4 and p63, two regulators controlling self-renewal of villous cytotrophoblasts. Our results revealed Notch1 as a key factor promoting development of progenitors of the extravillous trophoblast lineage in the human placenta.

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Villous culture of first trimester human placenta-model to study extravillous trophoblast (EVT) differentiation

Placenta ◽

10.1016/0143-4004(92)90051-t ◽

1992 ◽

Vol 13 (5) ◽

pp. 439-461 ◽

Cited By ~ 126

Author(s):

Olga Genbacev ◽

Stephanie A. Schubach ◽

Richard K. Miller

Keyword(s):

Human Placenta ◽

First Trimester ◽

Extravillous Trophoblast

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Expression of Endothelial Nitric Oxide Synthase by Extravillous Trophoblast Cells in the Human Placenta

Placenta ◽

10.1053/plac.1999.0428 ◽

2000 ◽

Vol 21 (1) ◽

pp. 23-31 ◽

Cited By ~ 46

Author(s):

D. Martin ◽

K.P. Conrad

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Human Placenta ◽

Endothelial Nitric Oxide Synthase ◽

Extravillous Trophoblast ◽

Trophoblast Cells ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

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Prediction of Non-canonical Routes for SARS-CoV-2 Infection in Human Placenta Cells

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.614728 ◽

2021 ◽

Vol 8 ◽

Author(s):

Flávia Bessi Constantino ◽

Sarah Santiloni Cury ◽

Celia Regina Nogueira ◽

Robson Francisco Carvalho ◽

Luis Antonio Justulin

Keyword(s):

Human Placenta ◽

Zika Virus ◽

Cell Entry ◽

Extravillous Trophoblast ◽

Rna Seq ◽

Host Proteins ◽

Congenital Infections ◽

Intrauterine Transmission ◽

Low Levels ◽

Insight Into

The SARS-CoV-2 is the causative agent of the COVID-19 pandemic. The data available about COVID-19 during pregnancy have demonstrated placental infection; however, the mechanisms associated with intrauterine transmission of SARS-CoV-2 is still debated. Intriguingly, while canonical SARS-CoV-2 cell entry mediators are expressed at low levels in placental cells, the receptors for viruses that cause congenital infections such as the cytomegalovirus and Zika virus are highly expressed in these cells. Here we analyzed the transcriptional profile (microarray and single-cell RNA-Seq) of proteins potentially interacting with coronaviruses to identify non- canonical mediators of SARS-CoV-2 infection and replication in the placenta. Despite low levels of the canonical cell entry mediators ACE2 and TMPRSS2, we show that cells of the syncytiotrophoblast, villous cytotrophoblast, and extravillous trophoblast co-express high levels of the potential non-canonical cell-entry mediators DPP4 and CTSL. We also found changes in the expression of DAAM1 and PAICS genes during pregnancy, which are translated into proteins also predicted to interact with coronaviruses proteins. These results provide new insight into the interaction between SARS-CoV-2 and host proteins that may act as non-canonical routes for SARS-CoV-2 infection and replication in the placenta cells.

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