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 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.

Exosomes Derived from miR-183-Overexpressing Human Adipose-Derived Stem Cells Alleviate Hepatic Ischemia-Reperfusion (I/R) Injury through miR-183/ALOX5 axisExosomes Derived from miR-183-Overexpressing Human Adipose-Derived Stem Cells Alleviate Hepatic Ischemia-Reperfusion (I/R) Injury through miR-183/ALOX5 Axis

“…Research manifested that LTA4, as an active lipid, critically related to in ammation. Currently, ALOX5 has been reported to be involved in the pathogenesis of multiple diseases, such as asthma, cardiovascular diseases, multiple sclerosis, tumors and allergic diseases, etc [59][60][61][62][63]. Our study further demonstrated that ALOX5 could dramatically reverse miR-183-medaited proliferation and apoptosis of HL-7702 cells with I/R injury, indicating that miR-183 could notably attenuate liver I/R injury by targeting ALOX5.…”

CXCL16/CXCR6 interaction promotes endometrial decidualization via the PI3K/AKT pathway

“…This means that trophoblast cells could produce multiple cytokines that participate in decidualization. As documented, the factors secreted by trophoblast cells such as profilin 1 could also induce the decidualization of human ESCs (Menkhorst et al 2017) In addition, trophoblasts-derived CXCL12 could promote the invasiveness of trophoblasts and enhances the coordination between trophoblasts and DSCs (Zhou et al 2008). CCL25, CCL8 and CXCL10 secreted by trophoblast cells can also be involved in embryo implantation (Sakumoto et al 2017, Weingrill et al 2018).…”

Metabolism of cholesterol and progesterone is differentially regulated in primary trophoblastic subtypes and might be disturbed in recurrent miscarriages

“…However, knowledge about the regulation of progesterone metabolism in trophoblasts derived from the critical first trimester is sparse so far: Genbacev, Schubach, and Miller (36) observed progesterone production in cultivated primary human villous explant cultures. Later on, progesterone secretion was also confirmed in primary EVT cultures (37).…”