Leukemia inhibitory factor enhances endometrial stromal cell decidualization in humans and mice.

Adequate differentiation or decidualization of endometrial stromal cells (ESC) is critical for successful pregnancy in humans and rodents. Here, we investigated the role of leukemia inhibitory factor (LIF) in human and murine decidualization. Ex vivo human (H) ESC decidualization was induced by estr...

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Autores principales:	Lorraine Lin Shuya, Ellen Melaleuca Menkhorst, Joanne Yap, Priscilla Li, Natalie Lane, Evdokia Dimitriadis
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9f34cd3d1ea647a29aafaa5a3e10f477
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spelling	oai:doaj.org-article:9f34cd3d1ea647a29aafaa5a3e10f4772021-11-04T06:07:53ZLeukemia inhibitory factor enhances endometrial stromal cell decidualization in humans and mice.1932-620310.1371/journal.pone.0025288https://doaj.org/article/9f34cd3d1ea647a29aafaa5a3e10f4772011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21966484/?tool=EBIhttps://doaj.org/toc/1932-6203Adequate differentiation or decidualization of endometrial stromal cells (ESC) is critical for successful pregnancy in humans and rodents. Here, we investigated the role of leukemia inhibitory factor (LIF) in human and murine decidualization. Ex vivo human (H) ESC decidualization was induced by estrogen (E, 10(-8) M) plus medroxyprogesterone acetate (MPA, 10(-7) M). Exogenous LIF (≥50 ng/ml) induced STAT3 phosphorylation in non-decidualized and decidualized HESC and enhanced E+MPA-induced decidualization (measured by PRL secretion, P<0.05). LIF mRNA in HESC was down-regulated by decidualization treatment (E+MPA) whereas LIF receptor (R) mRNA was up-regulated, suggesting that the decidualization stimulus 'primed' HESC for LIF action, but that factors not present in our in vitro model were required to induce LIF expression. Ex vivo first trimester decidual biopsies secreted >100 pg/mg G-CSF, IL6, IL8, and MCP1. Decidualized HESC secreted IL6, IL8, IL15 and MCP1. LIF (50 ng/ml) up-regulated IL6 and IL15 (P<0.05) secretion in decidualized HESC compared to 0.5 ng/ml LIF. In murine endometrium, LIF and LIFR immunolocalized to decidualized stromal cells on day 5 of gestation (day 0 = day of plug detection). Western blotting confirmed that LIF and the LIFR were up-regulated in intra-implantation sites compared to inter-implantation sites on Day 5 of gestation. To determine the role of LIF during in vivo murine decidualization, intra-peritoneal injections of a long-acting LIF antagonist (PEGLA; 900 or 1200 µg) were given just post-attachment, during the initiation of decidualization on day 4. PEGLA treatment reduced implantation site decidual area (P<0.05) and desmin staining immuno-intensity (P<0.05) compared to control on day 6 of gestation. This study demonstrated that LIF was an important regulator of decidualization in humans and mice and data provides insight into the processes underlying decidualization, which are important for understanding implantation and placentation.Lorraine Lin ShuyaEllen Melaleuca MenkhorstJoanne YapPriscilla LiNatalie LaneEvdokia DimitriadisEvdokia DimitriadisPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 9, p e25288 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lorraine Lin Shuya Ellen Melaleuca Menkhorst Joanne Yap Priscilla Li Natalie Lane Evdokia Dimitriadis Evdokia Dimitriadis Leukemia inhibitory factor enhances endometrial stromal cell decidualization in humans and mice.
description	Adequate differentiation or decidualization of endometrial stromal cells (ESC) is critical for successful pregnancy in humans and rodents. Here, we investigated the role of leukemia inhibitory factor (LIF) in human and murine decidualization. Ex vivo human (H) ESC decidualization was induced by estrogen (E, 10(-8) M) plus medroxyprogesterone acetate (MPA, 10(-7) M). Exogenous LIF (≥50 ng/ml) induced STAT3 phosphorylation in non-decidualized and decidualized HESC and enhanced E+MPA-induced decidualization (measured by PRL secretion, P<0.05). LIF mRNA in HESC was down-regulated by decidualization treatment (E+MPA) whereas LIF receptor (R) mRNA was up-regulated, suggesting that the decidualization stimulus 'primed' HESC for LIF action, but that factors not present in our in vitro model were required to induce LIF expression. Ex vivo first trimester decidual biopsies secreted >100 pg/mg G-CSF, IL6, IL8, and MCP1. Decidualized HESC secreted IL6, IL8, IL15 and MCP1. LIF (50 ng/ml) up-regulated IL6 and IL15 (P<0.05) secretion in decidualized HESC compared to 0.5 ng/ml LIF. In murine endometrium, LIF and LIFR immunolocalized to decidualized stromal cells on day 5 of gestation (day 0 = day of plug detection). Western blotting confirmed that LIF and the LIFR were up-regulated in intra-implantation sites compared to inter-implantation sites on Day 5 of gestation. To determine the role of LIF during in vivo murine decidualization, intra-peritoneal injections of a long-acting LIF antagonist (PEGLA; 900 or 1200 µg) were given just post-attachment, during the initiation of decidualization on day 4. PEGLA treatment reduced implantation site decidual area (P<0.05) and desmin staining immuno-intensity (P<0.05) compared to control on day 6 of gestation. This study demonstrated that LIF was an important regulator of decidualization in humans and mice and data provides insight into the processes underlying decidualization, which are important for understanding implantation and placentation.
format	article
author	Lorraine Lin Shuya Ellen Melaleuca Menkhorst Joanne Yap Priscilla Li Natalie Lane Evdokia Dimitriadis Evdokia Dimitriadis
author_facet	Lorraine Lin Shuya Ellen Melaleuca Menkhorst Joanne Yap Priscilla Li Natalie Lane Evdokia Dimitriadis Evdokia Dimitriadis
author_sort	Lorraine Lin Shuya
title	Leukemia inhibitory factor enhances endometrial stromal cell decidualization in humans and mice.
title_short	Leukemia inhibitory factor enhances endometrial stromal cell decidualization in humans and mice.
title_full	Leukemia inhibitory factor enhances endometrial stromal cell decidualization in humans and mice.
title_fullStr	Leukemia inhibitory factor enhances endometrial stromal cell decidualization in humans and mice.
title_full_unstemmed	Leukemia inhibitory factor enhances endometrial stromal cell decidualization in humans and mice.
title_sort	leukemia inhibitory factor enhances endometrial stromal cell decidualization in humans and mice.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/9f34cd3d1ea647a29aafaa5a3e10f477
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_version_	1718445165724565504

Leukemia inhibitory factor enhances endometrial stromal cell decidualization in humans and mice.

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