title: Interleukin 11 and activin A synergise to regulate progesterone-induced but not cAMP-induced decidualization.
abstract: Blastocyst implantation, placentation and the establishment of pregnancy in the human are dependent on the adequate decidualization of endometrial stromal cells. Locally produced and temporally regulated products such as interleukin 11 (IL11), and activin A are involved in this process; however, the molecular interactions that regulate decidualization are largely unknown. Here, we investigated whether IL11 and activin A interact to promote human endometrial stromal cell (HESC) decidualization using an in vitro model. HESCs, induced to decidualize by cAMP or progesterone, were treated with IL11, activin A or IL11 plus activin A combined and decidual progress was examined using prolactin as a decidual marker. Treatment with combined IL11 plus activin A enhanced progesterone-induced decidualization above control or treatment with IL11 or activin A alone. Treatment had no effect on cAMP-decidualized HESC. Investigation of IL11 and activin A stimulation of (respectively) activin A and IL11 expression in undifferentiated HESC was by real-time PCR and ELISA. Activin A treatment induced IL11 secretion and phosphorylation of the activin A signalling component, SMAD2 (measured by ELISA). Inclusion of the TGFbeta 1 receptor inhibitor, SB431542, in the activin A treatment, reduced pSMAD2 and IL11 secretion. This study suggests that activin A is an early inducer of decidualization, regulating the secretion of IL11. This data provides insight into the processes underlying decidualization, which are important for understanding implantation and placentation and have potential clinical applications for the regulation of fertility.
authors.affiliation: Prince Henry's Institute of Medical Research, PO Box 5152, Clayton, Victoria, 3168, Australia.
authors.forename: Ellen
authors.initials: E
authors.lastname: Menkhorst
authors.forename: Lois A
authors.initials: LA
authors.lastname: Salamonsen
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.forename: Craig A
authors.initials: CA
authors.lastname: Harrison
authors.forename: Jun
authors.initials: J
authors.lastname: Gu
authors.forename: Evdokia
authors.initials: E
authors.lastname: Dimitriadis
mesh_terms: D028341:Activins / Q000378:metabolism / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D003656:Decidua / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004149:Dioxoles / Q000494:pharmacology; D004717:Endometrium / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D017370:Interleukin-11 / Q000378:metabolism / Q000494:pharmacology*; D011247:Pregnancy; D011374:Progesterone / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D004149:Dioxoles; D017370:Interleukin-11; D018125:Receptors, Transforming Growth Factor beta; D051899:Smad2 Protein; C422405:activin A; D028341:Activins; D011374:Progesterone; D000242:Cyclic AMP