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

Shuya, Lorraine Lin ; Menkhorst, Ellen Melaleuca ; Yap, Joanne ; Li, Priscilla ; Lane, Natalie ; Dimitriadis, Evdokia Wutz, Anton

PloS one, 2011-09, Vol.6 (9), p.e25288-e25288 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Leukemia inhibitory factor enhances endometrial stromal cell decidualization in humans and mice
Autor: Shuya, Lorraine Lin ; Menkhorst, Ellen Melaleuca ; Yap, Joanne ; Li, Priscilla ; Lane, Natalie ; Dimitriadis, Evdokia
Wutz, Anton
Assuntos: Acetic acid ; Animals ; Biology ; Biopsy ; Blotting, Western ; Cells, Cultured ; Cytokines ; Decidua ; Decidua - cytology ; Decidua - drug effects ; Decidua - metabolism ; Desmin ; Desmin - genetics ; Desmin - metabolism ; Developmental biology ; Embryo Implantation - physiology ; Endometrium ; Endometrium - cytology ; Endometrium - drug effects ; Endometrium - metabolism ; Enzyme-Linked Immunosorbent Assay ; Estrogens ; Ethics ; Female ; Females ; Gestation ; Granulocyte colony-stimulating factor ; Humans ; Immunohistochemistry ; Implantation ; In Vitro Techniques ; In vivo methods and tests ; Interleukin 1 ; Interleukin 15 ; Interleukin 6 ; Interleukin 8 ; Laboratories ; Leukemia ; Leukemia inhibitory factor ; Leukemia Inhibitory Factor - genetics ; Leukemia Inhibitory Factor - metabolism ; Leukemia Inhibitory Factor - pharmacology ; Leukemia Inhibitory Factor Receptor alpha Subunit - antagonists & inhibitors ; Leukemia Inhibitory Factor Receptor alpha Subunit - genetics ; Leukemia Inhibitory Factor Receptor alpha Subunit - metabolism ; Ligands ; Medicine ; Medroxyprogesterone acetate ; Melaleuca ; Menstruation ; Mesocricetus auratus ; Mice ; mRNA ; Peritoneum ; Phosphorylation ; Polyethylene glycol ; Polymerase Chain Reaction ; Pregnancy ; Pregnancy Trimester, First - genetics ; Pregnancy Trimester, First - metabolism ; Proteins ; Rodentia ; Rodents ; Stat3 protein ; STAT3 Transcription Factor - genetics ; STAT3 Transcription Factor - metabolism ; Stromal cells ; Surgical implants ; Western blotting ; Womens health
É parte de: PloS one, 2011-09, Vol.6 (9), p.e25288-e25288
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Conceived and designed the experiments: EM ED. Performed the experiments: LS EM JY PL NL. Analyzed the data: LS EM. Contributed reagents/materials/analysis tools: ED. Wrote the paper: LS EM ED.
Descrição: 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.
Editor: United States: Public Library of Science
Idioma: Inglês

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

Shuya, Lorraine Lin ; Menkhorst, Ellen Melaleuca ; Yap, Joanne ; Li, Priscilla ; Lane, Natalie ; Dimitriadis, Evdokia Wutz, Anton

United States: Public Library of Science

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