Granulocyte-Colony Stimulating Factor related pathways tested on an endometrial ex-vivo model.

<h4>Introduction</h4>Recombinant human Granulocyte-Colony Stimulating Factor (rhG-CSF) supplementation seems to be a promising innovative therapy in reproductive medicine, used in case of recurrent miscarriage, embryo implantation failure or thin endometrium, although its mechanisms of a...

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Autores principales:	Mona Rahmati, Marie Petitbarat, Sylvie Dubanchet, Armand Bensussan, Gerard Chaouat, Nathalie Ledee
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b4e5e57e28034a9ab32b9c5c388ae005
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spelling	oai:doaj.org-article:b4e5e57e28034a9ab32b9c5c388ae0052021-11-25T05:58:13ZGranulocyte-Colony Stimulating Factor related pathways tested on an endometrial ex-vivo model.1932-620310.1371/journal.pone.0102286https://doaj.org/article/b4e5e57e28034a9ab32b9c5c388ae0052014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0102286https://doaj.org/toc/1932-6203<h4>Introduction</h4>Recombinant human Granulocyte-Colony Stimulating Factor (rhG-CSF) supplementation seems to be a promising innovative therapy in reproductive medicine, used in case of recurrent miscarriage, embryo implantation failure or thin endometrium, although its mechanisms of action remain unknown. Our aim was to identify possible endometrial pathways influenced by rhG-CSF.<h4>Materials and methods</h4>Hypothetical molecular interactions regulated by G-CSF were designed through a previous large scale endometrial microarray study. The variation of endometrial expression of selected target genes was confirmed in control and infertile patients. G-CSF supplementation influence on these targets was tested on an endometrial ex-vivo culture. Middle luteal phase endometrial biopsies were cultured on collagen sponge with or without rhG-CSF supplementation during 3 consecutive days. Variations of endometrial mRNA expression for the selected targets were studied by RT-PCR.<h4>Results</h4>At the highest dose of rhG-CSF stimulation, the mRNA expression of these selected target genes was significantly increased if compared with their expression without addition of rhG-CSF. The selected targets were G-CSF Receptor (G-CSFR), Integrin alpha-V/beta-3 (ITGB3) implicated in cell migration and embryo implantation, Plasminogen Activator Urokinase Receptor (PLAUR) described as interacting with integrins and implicated in cell migration, Thymidine Phosphorylase (TYMP) implicated in local angiogenesis, CD40 and its ligand CD40L involved in cell proliferation control.<h4>Conclusion</h4>RhG-CSF seems able to influence endometrial expressions crucial for implantation process involving endometrial vascular remodelling, local immune modulation and cellular adhesion pathways. These variations observed in an ex-vivo model should be tested in-vivo. The strict indications or counter indication of rhG-CSF supplementation in reproductive field are not yet established, while the safety of its administration in early pregnancy on early embryogenesis still needs to be demonstrated. Nevertheless, rhG-CSF appears as a promising therapy in some difficult and unsolved cases of reproductive failure. Indications of pre-conceptual rhG-CSF supplementation may derive from a diagnosed lack of endometrial expression of some target genes.Mona RahmatiMarie PetitbaratSylvie DubanchetArmand BensussanGerard ChaouatNathalie LedeePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 9, p e102286 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mona Rahmati Marie Petitbarat Sylvie Dubanchet Armand Bensussan Gerard Chaouat Nathalie Ledee Granulocyte-Colony Stimulating Factor related pathways tested on an endometrial ex-vivo model.
description	<h4>Introduction</h4>Recombinant human Granulocyte-Colony Stimulating Factor (rhG-CSF) supplementation seems to be a promising innovative therapy in reproductive medicine, used in case of recurrent miscarriage, embryo implantation failure or thin endometrium, although its mechanisms of action remain unknown. Our aim was to identify possible endometrial pathways influenced by rhG-CSF.<h4>Materials and methods</h4>Hypothetical molecular interactions regulated by G-CSF were designed through a previous large scale endometrial microarray study. The variation of endometrial expression of selected target genes was confirmed in control and infertile patients. G-CSF supplementation influence on these targets was tested on an endometrial ex-vivo culture. Middle luteal phase endometrial biopsies were cultured on collagen sponge with or without rhG-CSF supplementation during 3 consecutive days. Variations of endometrial mRNA expression for the selected targets were studied by RT-PCR.<h4>Results</h4>At the highest dose of rhG-CSF stimulation, the mRNA expression of these selected target genes was significantly increased if compared with their expression without addition of rhG-CSF. The selected targets were G-CSF Receptor (G-CSFR), Integrin alpha-V/beta-3 (ITGB3) implicated in cell migration and embryo implantation, Plasminogen Activator Urokinase Receptor (PLAUR) described as interacting with integrins and implicated in cell migration, Thymidine Phosphorylase (TYMP) implicated in local angiogenesis, CD40 and its ligand CD40L involved in cell proliferation control.<h4>Conclusion</h4>RhG-CSF seems able to influence endometrial expressions crucial for implantation process involving endometrial vascular remodelling, local immune modulation and cellular adhesion pathways. These variations observed in an ex-vivo model should be tested in-vivo. The strict indications or counter indication of rhG-CSF supplementation in reproductive field are not yet established, while the safety of its administration in early pregnancy on early embryogenesis still needs to be demonstrated. Nevertheless, rhG-CSF appears as a promising therapy in some difficult and unsolved cases of reproductive failure. Indications of pre-conceptual rhG-CSF supplementation may derive from a diagnosed lack of endometrial expression of some target genes.
format	article
author	Mona Rahmati Marie Petitbarat Sylvie Dubanchet Armand Bensussan Gerard Chaouat Nathalie Ledee
author_facet	Mona Rahmati Marie Petitbarat Sylvie Dubanchet Armand Bensussan Gerard Chaouat Nathalie Ledee
author_sort	Mona Rahmati
title	Granulocyte-Colony Stimulating Factor related pathways tested on an endometrial ex-vivo model.
title_short	Granulocyte-Colony Stimulating Factor related pathways tested on an endometrial ex-vivo model.
title_full	Granulocyte-Colony Stimulating Factor related pathways tested on an endometrial ex-vivo model.
title_fullStr	Granulocyte-Colony Stimulating Factor related pathways tested on an endometrial ex-vivo model.
title_full_unstemmed	Granulocyte-Colony Stimulating Factor related pathways tested on an endometrial ex-vivo model.
title_sort	granulocyte-colony stimulating factor related pathways tested on an endometrial ex-vivo model.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/b4e5e57e28034a9ab32b9c5c388ae005
work_keys_str_mv	AT monarahmati granulocytecolonystimulatingfactorrelatedpathwaystestedonanendometrialexvivomodel AT mariepetitbarat granulocytecolonystimulatingfactorrelatedpathwaystestedonanendometrialexvivomodel AT sylviedubanchet granulocytecolonystimulatingfactorrelatedpathwaystestedonanendometrialexvivomodel AT armandbensussan granulocytecolonystimulatingfactorrelatedpathwaystestedonanendometrialexvivomodel AT gerardchaouat granulocytecolonystimulatingfactorrelatedpathwaystestedonanendometrialexvivomodel AT nathalieledee granulocytecolonystimulatingfactorrelatedpathwaystestedonanendometrialexvivomodel
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Granulocyte-Colony Stimulating Factor related pathways tested on an endometrial ex-vivo model.

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