title: The production of interleukin-11 and decidualization are compromised in endometrial stromal cells derived from patients with infertility.
abstract: IL-11 signaling is critical for decidualization of the endometrial stroma in early pregnancy in the mouse. In this study, we investigate the function of IL-11 signaling in cAMP-induced decidualization of human endometrial stromal cells. We show that treatment of endometrial stromal cells with 8-bromo-cAMP (8-Br-cAMP) results in an increase in the levels of secreted IL-11, whereas levels of cell surface IL-11 receptor alpha are similar with or without 8-Br-cAMP treatment. The production of IL-11 correlates with the production of molecular markers of decidualization, prolactin and IGF-binding protein-1. The expression of these markers is inhibited when IL-11 signaling is specifically blocked in decidualizing endometrial stromal cells by the IL-11 antagonist W147A. We demonstrate that 8-Br-cAMP-induced endometrial stromal cells derived from patients with primary infertility produce lower levels of prolactin, IGF-binding protein-1, and IL-11 than cells derived from fertile women. Our results suggest that IL-11 expression is critically important during decidualization in the human endometrium, and that aberrant regulation of endometrial IL-11 production may be associated with some types of infertility.
authors.affiliation: Nuffield Department of Obstetrics and Gynecology, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom.
authors.forename: Natalia
authors.initials: N
authors.lastname: Karpovich
authors.forename: Petra
authors.initials: P
authors.lastname: Klemmt
authors.forename: Jung Hye
authors.initials: JH
authors.lastname: Hwang
authors.forename: J Enda
authors.initials: JE
authors.lastname: McVeigh
authors.forename: John K
authors.initials: JK
authors.lastname: Heath
authors.forename: David H
authors.initials: DH
authors.lastname: Barlow
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Mardon
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000328:Adult; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D003656:Decidua / Q000502:physiology*; D004717:Endometrium / Q000166:cytology / Q000502:physiology; D005260:Female; D006801:Humans; D007247:Infertility, Female / Q000378:metabolism*; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism; D017370:Interleukin-11 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053703:Interleukin-11 Receptor alpha Subunit; D011388:Prolactin / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D053702:Receptors, Interleukin-11; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: C508428:IL11RA protein, human; C508429:Il11ra1 protein, mouse; C508431:Il11ra2 protein, mouse; D018970:Insulin-Like Growth Factor Binding Protein 1; D017370:Interleukin-11; D053703:Interleukin-11 Receptor alpha Subunit; D018123:Receptors, Interleukin; D053702:Receptors, Interleukin-11; D015124:8-Bromo Cyclic Adenosine Monophosphate; D011388:Prolactin; D000242:Cyclic AMP