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Decidual Differentiation of Stromal Cells Promotes Proprotein Convertase 5/6 Expression and Lefty Processing

Department of Obstetrics and Gynecology (M.T., A.M., S.T.), Stony Brook University, Stony Brook, New York 11794; Laboratory for Molecular Cell Biology (I.P., J.W.M.C.), Department for Human Genetics, University of Leuven and Flanders Interuniversity Institute for Biotechnology, B-3000 Leuven, Belgium; Department of Gynecology and Obstetrics (L.C.G., S.T.), Stanford University Medical Center, Stanford, California 94305; Department of Obstetrics and Gynecology (A.T.F.), University of Illinois at Chicago, Chicago, Illinois 60612; Department of Biological Sciences (D.D.C.), University of Delaware, Newark, Delaware 19707; and Department of Laboratory Pathology and Medicine (D.G.K., C.B.), Division of Reproductive Endocrinology and Infertility, University of North Carolina, Chapel Hill, North Carolina 27599

Address all correspondence and requests for reprints to: S. Tabibzadeh, M.D., Frontiers in Bioscience, PO Box 160, Searingtown, New York 11507. E-mail: tabibzadeh{at}bioscience.org.

Lefty/Ebaf polypeptides, novel members of the TGF-ß superfamily, are involved in endometrial differentiation and embryo implantation. Recently, we showed that, during undisturbed estrous cycle, lefty is present in mouse uterine horn primarily in a precursor form. Here, we show that decidual differentiation of endometrial stroma leads to increased lefty (3.1- to 3.6-fold in vivo and 5- to 8-fold in vitro) and processing of its precursor primarily to its long form. This event occurs on d 5 of pregnancy, and is paralleled by proprotein convertase (PC)5/6 up-regulation (6-fold increase for PC5A and 3-fold increase for PC5B) in decidualized uterine horn, independent of embryo implantation. Among the known convertases, only PC5/6A processes lefty to its long form. Taken together, the findings show that decidualized differentiation of stroma, which is a prerequisite for embryo implantation, leads to processing of lefty by PC5/6A.

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