Invasive trophoblast promote stromal fibroblast decidualization via Profilin 1 and ALOX5

Abstract During the establishment of pregnancy, extravillous trophoblast (EVT) must invade into the uterine decidua to facilitate decidual artery remodelling to create the placental blood supply. The local decidual environment is thought to regulate trophoblast invasion, however these interactions a...

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Main Authors: E. M. Menkhorst, M. L. Van Sinderen, K. Rainczuk, C. Cuman, A. Winship, E. Dimitriadis
Format: Article
Language:English
Published: Nature Portfolio 2017-08-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-017-05947-0
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author E. M. Menkhorst
M. L. Van Sinderen
K. Rainczuk
C. Cuman
A. Winship
E. Dimitriadis
author_facet E. M. Menkhorst
M. L. Van Sinderen
K. Rainczuk
C. Cuman
A. Winship
E. Dimitriadis
author_sort E. M. Menkhorst
collection DOAJ
description Abstract During the establishment of pregnancy, extravillous trophoblast (EVT) must invade into the uterine decidua to facilitate decidual artery remodelling to create the placental blood supply. The local decidual environment is thought to regulate trophoblast invasion, however these interactions are poorly defined in humans. Recent evidence in women suggests impaired decidualization is associated with miscarriage and preeclampsia. Primary human endometrial stromal cells (HESC) and first trimester extravillous trophoblast (EVTs) were used to assess the effect of EVT-secreted factors on HESC decidualization, adhesion, proliferation and migration. We determined the role of profilin (PFN)1, an EVT-secreted factor, on HESC function and identified a downstream target of PFN1. EVT-secreted factors induced HESC decidualization and enhanced decidualized HESC adhesion, proliferation and migration. Recombinant PFN1 enhanced methoxyprogesterone acetate-induced HESC decidualization and proliferation. PFN1 down-regulated the expression of lipoxygenase arachidonate 5-lipoxygenase (ALOX5) in HESC and THP-1 macrophages. ALOX5 localised to decidual cells and CD68+macrophages in 1st trimester decidua. This study demonstrated that EVT secretions, including PFN1, enhanced HESC decidualization and motility. This study has identified a new pathway that facilitates appropriate decidualization during the establishment of pregnancy.
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spelling doaj.art-9feba91aa68c41ba9162df6811a207342022-12-21T22:56:55ZengNature PortfolioScientific Reports2045-23222017-08-017111110.1038/s41598-017-05947-0Invasive trophoblast promote stromal fibroblast decidualization via Profilin 1 and ALOX5E. M. Menkhorst0M. L. Van Sinderen1K. Rainczuk2C. Cuman3A. Winship4E. Dimitriadis5Hudson Institute of Medical ResearchHudson Institute of Medical ResearchHudson Institute of Medical ResearchHudson Institute of Medical ResearchHudson Institute of Medical ResearchHudson Institute of Medical ResearchAbstract During the establishment of pregnancy, extravillous trophoblast (EVT) must invade into the uterine decidua to facilitate decidual artery remodelling to create the placental blood supply. The local decidual environment is thought to regulate trophoblast invasion, however these interactions are poorly defined in humans. Recent evidence in women suggests impaired decidualization is associated with miscarriage and preeclampsia. Primary human endometrial stromal cells (HESC) and first trimester extravillous trophoblast (EVTs) were used to assess the effect of EVT-secreted factors on HESC decidualization, adhesion, proliferation and migration. We determined the role of profilin (PFN)1, an EVT-secreted factor, on HESC function and identified a downstream target of PFN1. EVT-secreted factors induced HESC decidualization and enhanced decidualized HESC adhesion, proliferation and migration. Recombinant PFN1 enhanced methoxyprogesterone acetate-induced HESC decidualization and proliferation. PFN1 down-regulated the expression of lipoxygenase arachidonate 5-lipoxygenase (ALOX5) in HESC and THP-1 macrophages. ALOX5 localised to decidual cells and CD68+macrophages in 1st trimester decidua. This study demonstrated that EVT secretions, including PFN1, enhanced HESC decidualization and motility. This study has identified a new pathway that facilitates appropriate decidualization during the establishment of pregnancy.https://doi.org/10.1038/s41598-017-05947-0
spellingShingle E. M. Menkhorst
M. L. Van Sinderen
K. Rainczuk
C. Cuman
A. Winship
E. Dimitriadis
Invasive trophoblast promote stromal fibroblast decidualization via Profilin 1 and ALOX5
Scientific Reports
title Invasive trophoblast promote stromal fibroblast decidualization via Profilin 1 and ALOX5
title_full Invasive trophoblast promote stromal fibroblast decidualization via Profilin 1 and ALOX5
title_fullStr Invasive trophoblast promote stromal fibroblast decidualization via Profilin 1 and ALOX5
title_full_unstemmed Invasive trophoblast promote stromal fibroblast decidualization via Profilin 1 and ALOX5
title_short Invasive trophoblast promote stromal fibroblast decidualization via Profilin 1 and ALOX5
title_sort invasive trophoblast promote stromal fibroblast decidualization via profilin 1 and alox5
url https://doi.org/10.1038/s41598-017-05947-0
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