The role of leukemia inhibitory factor in tubal ectopic pregnancy.

Krishnan, T; Winship, A; Sonderegger, S; Menkhorst, E; Horne, A W; Brown, J; Zhang, J-G; Nicola, N A; Tong, S; Dimitriadis, E

Krishnan, T; Winship, A; Sonderegger, S; Menkhorst, E; Horne, A W; Brown, J; Zhang, J-G; Nicola, N A; Tong, S; Dimitriadis, E.

Afiliación

Krishnan T; Prince Henry's Institute of Medical Research, P.O. Box 5152, Clayton, Victoria 3168, Australia; Faculty of Medicine, Nursing & Health Sciences, Wellington Road, Monash University, Clayton, Victoria 3800, Australia.

Placenta ; 34(11): 1014-9, 2013 Nov.

Article en En | MEDLINE | ID: mdl-24074901

RESUMEN

INTRODUCTION: Ectopic pregnancy is unique to humans and a leading cause of maternal morbidity and mortality. The etiology remains unknown however factors regulating embryo implantation likely contribute. Leukemia inhibitory factor (LIF) has roles in extravillous trophoblast adhesion and invasion and is present in ectopic implantation sites. We hypothesised that LIF facilitates blastocyst adhesion/invasion in the Fallopian tube, contributing to ectopic pregnancy. METHODS: We immunolocalised LIF receptor (R) in tubal ectopic pregnancy (N = 5). We used an oviduct cell line (OE-E6/E7) to model Fallopian tube epithelial cells and a trophoblast spheroid co-culture model (HTR-8/SVneo cell line formed spheroids) to model blastocyst attachment to the Fallopian tube. We examined LIF signaling pathways in OE-E6/E7 cells by Western blot. The effect of LIF and LIF inhibition (using a novel LIF inhibitor, PEGLA) on first-trimester placental outgrowth was determined. RESULTS: LIFR localised to villous and extravillous trophoblast and Fallopian tube epithelium in ectopic pregnancy. LIF activated STAT3 but not the ERK pathway in OE-E6/E7 cells. LIF stimulated HTR-8/SVneo spheroid adhesion to OE-E6/E7 cells which was significantly reduced after PEGLA treatment. LIF promoted placental explants outgrowth, while co-treatment with PEGLA blocked outgrowth. DISCUSSION: Our data suggests LIF facilitates the development of ectopic pregnancy by stimulating blastocyst adhesion and trophoblast outgrowth from placental explants. Ectopic pregnancy is usually diagnosed after 6 weeks of pregnancy, therefore PEGLA may be useful in targeting trophoblast growth/invasion. CONCLUSION: LIF may contribute to the development of ectopic pregnancies and that pharmacologically targeting LIF-mediated trophoblast outgrowth may be useful as a treatment for ectopic pregnancy.

Asunto(s)

Blastocisto/metabolismo; Trompas Uterinas/metabolismo; Subunidad alfa del Receptor del Factor Inhibidor de Leucemia/metabolismo; Factor Inhibidor de Leucemia/metabolismo; Placenta/metabolismo; Embarazo Tubario/metabolismo; Transducción de Señal; Adolescente; Adulto; Blastocisto/efectos de los fármacos; Blastocisto/patología; Adhesión Celular/efectos de los fármacos; Línea Celular; Proliferación Celular/efectos de los fármacos; Técnicas de Cocultivo; Implantación del Embrión/efectos de los fármacos; Epitelio/efectos de los fármacos; Epitelio/metabolismo; Epitelio/patología; Trompas Uterinas/efectos de los fármacos; Trompas Uterinas/patología; Trompas Uterinas/cirugía; Femenino; Humanos; Factor Inhibidor de Leucemia/antagonistas & inhibidores; Factor Inhibidor de Leucemia/genética; Factor Inhibidor de Leucemia/farmacología; Subunidad alfa del Receptor del Factor Inhibidor de Leucemia/agonistas; Subunidad alfa del Receptor del Factor Inhibidor de Leucemia/antagonistas & inhibidores; Subunidad alfa del Receptor del Factor Inhibidor de Leucemia/genética; Persona de Mediana Edad; Placenta/efectos de los fármacos; Placenta/patología; Polietilenglicoles/farmacología; Embarazo; Embarazo Tubario/patología; Embarazo Tubario/cirugía; Factor de Transcripción STAT3/agonistas; Factor de Transcripción STAT3/antagonistas & inhibidores; Factor de Transcripción STAT3/metabolismo; Transducción de Señal/efectos de los fármacos; Esferoides Celulares; Técnicas de Cultivo de Tejidos; Adulto Joven

Palabras clave

EVT; Ectopic; Implantation; Leukemia inhibitory factor; Placenta; Pregnancy

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Placenta / Embarazo Tubario / Blastocisto / Transducción de Señal / Factor Inhibidor de Leucemia / Subunidad alfa del Receptor del Factor Inhibidor de Leucemia / Trompas Uterinas Tipo de estudio: Prognostic_studies Idioma: En Revista: Placenta Año: 2013 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Países Bajos

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