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Submitted on June 7, 2005
Accepted on August 23, 2005
Dept of Obstetrics and Gynecology, Stony Brook University, Stony Brook, NY; Laboratory for Molecular Cell Biology, Department for Human Genetics, University of Leuven and Flanders Interuniversity Institute for Biotechnology, Herestraat 49, B-3000 Leuven, Belgium; Department of Gynecology and Obstetrics, Stanford University Medical Center, Stanford, California; Department of Obstetrics and Gynecology, University of Illinois at Chicago, Chicago, IL 60612; Department of Biological Sciences, University of Delaware, Newark 19707; Department of Laboratory Pathology and Medicine, Division of Reproductive Endocrinology and Infertility, University of North Carolina at Chapel Hill, North Carolina
* To whom correspondence should be addressed. E-mail: tabibzadeh{at}bioscience.org.
Lefty/Ebaf polypeptides, novel members of the TGF-
superfamily, are involved in endometrial differentiation and embryo implantation. Recently, we showed that during un-disturbed 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 (
3.1-3.6 fold in vivo and 5- to 8-fold in vitro) and processing of its precursor primarily to its long form. This event occurs on day five of pregnancy, and is paralleled by PC5/6 up-regulation ( 6 fold increase for PC5A and 3 fold increase for PC5B) in decidualized uterine horn. These events can be replicated by artificial decidualization of stroma 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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