title: Isolation, characterization, and function of EBAF/LEFTY B: role in infertility.
abstract: Human endometrium exhibits cyclic stromal and glandular remodeling in preparation of embryo implantation. We identified EBAF/LEFTY B as a soluble cytokine of the TGF-β superfamily that is expressed at a low level in human endometrium during the receptivity period, while it is maximally expressed during perimenstrual and menstrual phases. Transfection of cells with EBAF/LEFTY B resulted in expression of a 42 kD protein that was proteolytically processed to release two polypeptides of 34 and 28 kD. EBAF/LEFTY B causes tissue remodeling by induction of collagenolysis by matrix metalloproteases. In a subset of infertile patients, the expression EBAF/LEFTY B was prematurely increased during the implantation window. We showed that induced overexpression of EBAF/LEFTY B in transgenic mice impairs implantation. EBAF/LEFTY B inhibits the expression of key decidual proteins, IGFBP-1 and PRL, through regulation of transcription factors FOXO1 and ETS1. Together, these findings show that during embryonic development, EBAF/LEFTY B plays important roles in decidualization and embryo implantation.
authors.affiliation: Department of Obstetrics and Gynecology, Stony Brook University, Stony Brook, New York, USA. fbs@bioscience.org
authors.forename: Siamak
authors.initials: S
authors.lastname: Tabibzadeh
mesh_terms: D010064:Embryo Implantation / Q000502:physiology; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D006801:Humans; D007247:Infertility, Female / Q000378:metabolism*; D055458:Left-Right Determination Factors / Q000378:metabolism*; D011247:Pregnancy
chemical_list: C526161:LEFTY1 protein, human; C411603:LEFTY2 protein, human; D055458:Left-Right Determination Factors