Related Experiment Video

Updated: Jan 26, 2026

In Vitro Assays to Evaluate the Migration, Invasion, and Proliferation of Immortalized Human First-trimester Trophoblast Cell Lines
09:57

In Vitro Assays to Evaluate the Migration, Invasion, and Proliferation of Immortalized Human First-trimester Trophoblast Cell Lines

Published on: March 5, 2019

10.7K

Faulty oxygen sensing disrupts angiomotin function in trophoblast cell migration and predisposes to preeclampsia

Abby Farrell1,2, Sruthi Alahari1,3, Leonardo Ermini1

  • 1Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.

JCI Insight
|April 19, 2019
PubMed

Human placenta development and a successful pregnancy is incumbent upon precise oxygen-dependent control of trophoblast migration/invasion. Persistent low oxygen leading to failed trophoblast invasion promotes inadequate spiral artery remodeling, a characteristic of preeclampsia. Angiomotin (AMOT) is a multifaceted scaffolding protein involved in cell polarity and migration, yet its upstream regulation and significance in the human placenta remain unknown. Herein, we show that AMOT is primarily expressed in migratory extravillous trophoblast cells (EVTs) of the intermediate and distal anchoring column. Its expression increases after 10 weeks of gestation when oxygen tension rises and EVT migration/invasion peaks. Time-lapse imaging confirmed that the AMOT 80-kDa isoform promotes migration of trophoblastic JEG3 and HTR-8/SVneo cells. In preeclampsia, however, AMOT expression is decreased and its localization to migratory fetomaternal interface EVTs is disrupted. We demonstrate that Jumonji C domain-containing protein 6 (JMJD6), an oxygen sensor, positively regulates AMOT via oxygen-dependent lysyl hydroxylation. Furthermore, in vitro and ex vivo studies show that transforming growth factor-β (TGF-β) regulates AMOT expression, its interaction with polarity protein PAR6, and its subcellular redistribution from tight junctions to cytoskeleton. Our data reveal an oxygen- and TGF-β-driven migratory function for AMOT in the human placenta, and implicate its deficiency in impaired trophoblast migration that plagues preeclampsia.

Keywords:
Cell BiologyCell migration/adhesionObstetrics/gynecologyReproductive Biologyhypoxia

More Related Videos

Isolation of Primary Mouse Trophoblast Cells and Trophoblast Invasion Assay10:28

Isolation of Primary Mouse Trophoblast Cells and Trophoblast Invasion Assay

Published on: January 8, 2012

24.8K
Human Primary Trophoblast Cell Culture Model to Study the Protective Effects of Melatonin Against Hypoxia/reoxygenation-induced Disruption12:02

Human Primary Trophoblast Cell Culture Model to Study the Protective Effects of Melatonin Against Hypoxia/reoxygenation-induced Disruption

Published on: July 30, 2016

16.5K

Related Concept Videos

Cell Migration01:19

Cell Migration

Cell migration is a process by which the cells move from one location to another, playing an essential role in embryological development, repair and regeneration, immune response, and metastasis. Cells migrate in response to chemical or mechanical signals generated by specific organs or tissues. The overall mechanism includes three steps - polarization, protrusion, and release. Polarization involves the formation of a distinct cell front and rear, which determines the direction of movement.
6.5K
Cell Migration01:09

Cell Migration

Cell migration, the process by which cells move from one location to another, is essential for the proper development and viability of organisms throughout their life. When cells are not able to migrate properly to their ordained locations, various disorders may occur. For example, disruption in cell migration causes chronic inflammatory diseases such as arthritis.
18.7K
The Sense of Self: Reflected Self-Appraisal and Social Comparison02:57

The Sense of Self: Reflected Self-Appraisal and Social Comparison

According to Charles Cooley, we base our image on what we think other people see (Cooley 1902). We imagine how we must appear to others, then react to this speculation. We don certain clothes, prepare our hair in a particular manner, wear makeup, use cologne, and the like—all with the notion that our presentation of ourselves is going to affect how others perceive us. We expect a certain reaction, and, if lucky, we get the one we desire and feel good about it. But more than that, Cooley...
55.6K
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
3.2K
Chemotaxis and Direction of Cell Migration01:21

Chemotaxis and Direction of Cell Migration

Cells can detect chemical cues in their environment and reorganize the cytoskeleton to migrate toward them or away from them. This directional migration, called chemotaxis, is essential during embryogenesis and development, immune response, tissue repair and regeneration, and reproduction. These chemical cues can either attract or repel the cell's movement. For example, axon development is determined by a combination of chemoattractants and chemorepellents that direct the growing axon...
4.5K
Role of Myosin in Cell Migration01:18

Role of Myosin in Cell Migration

Myosins are multimeric motor proteins involved in various cellular processes such as migration, adhesion, and proliferation. Myosin II is the most common type in animal cells, which binds and cross-links actin filaments.
Myosin II  is a hexamer comprising two heavy chains with globular heads and coiled-coil tails, two regulatory light chains, and two essential light chains. The ATPase sites on the myosin heads hydrolyze ATP, and the released phosphate generates the force for contraction....
3.2K