Subtilisin proprotein convertase‐6 expression in the mouse uterus during implantation and artificially induced decidualization

Abstract

During implantation, a balance of factors regulates the invasive properties of the embryo and the anti-invasive properties of uterine decidua. Although antiproteinases such as the metalloproteinase inhibitor TIMP-3 are thought to play critical roles in preventing the overaggressive invasion of trophoblasts, the mechanism of antiproteinase regulation is unknown. Recently, the prohormone convertase SPC-6 has been found to be co-expressed in embryo-proximal decidua in association with TIMP-3. As members of this serine proteinase family are known to activate latent TGFbeta family members which regulate decidual TIMP-3 levels, we sought to characterize the expression of SPC-6 during pregnancy and artificial decidualization. In this study, we demonstrate that the zone of SPC-6 gene expression exhibits a great degree of temporal and spatial overlap with TIMP-3 gene expression in uterine decidua from E5.5 through to E8.5. Like TIMP-3, we demonstrate that SPC-6 expression is induced during the decidual cell response using an in vivo model of artificial decidualization. Both the secreted and membrane bound forms of SPC-6 are expressed throughout the period of decidualization, suggesting that SPC-6 may play multiple roles during this developmental period. This is confirmed by our observation of the movement of SPC-6 expression to the presumptive placental region, as TIMP-3 expression regresses at the implantation site.

Specific and Transient Up-Regulation of Proprotein Convertase 6 at the Site of Embryo Implantation and Identification of a Unique Transcript in Mouse Uterus During Early Pregnancy1

“…Just prior to the submission of this report, expression of PC6 was reported by Wong et al [12] in the mouse uterus during implantation. Overall, our data confirm those of that study but more clearly illustrate cell-specific expression of PC6 in the mouse uterus during implantation and, in particular, its differential expression between implantation and interimplantation sites.…”

“…Wong et al [12] proposed that PC6 might participate in the regulation of tissue inhibitor of metalloproteinase 3 during implantation. However, more data are needed to support this hypothesis.…”

“…Although Wong et al [12] recently reported the uterine expression of PC6 mRNA in the mouse and indicated its involvement during decidualization, the roles of PC6 in the uterus and particularly during embryo implantation have not been well studied. In the present investigation, we examined the uterine expression of PC6 mRNA in mice during early pregnancy, in particular at implantation and interimplantation sites at the time of implantation.…”

The Cysteine-rich Domain of the Secreted Proprotein Convertases PC5A and PACE4 Functions as a Cell Surface Anchor and Interacts with Tissue Inhibitors of Metalloproteinases

“…We also tested the possible interaction of PC5 with other TIMPs (e.g., TIMP-1, -3, and -4), especially in view of the fact that the mRNA levels of TIMP-3 and PC5A are coordinately regulated, and both are coexpressed during placental embryonic implantation and decidualization (Rancourt and Rancourt, 1997;Wong et al, 2002) and are possibly involved in the cell surface processing of zona pellucida domain proteins (Jovine et al, 2004). In addition, PC5A can process TGF␤-like (usually antiproliferative) proteins (Dubois et al, 2001;Ulloa et al, 2001) and active TGF␤ regulates the expression of TIMP-3 (Leco et al, 1994).…”

Angiopoietin-like gene expression in the mouse uterus during implantation and in response to steroids

“…Therefore, regulation of ANGPTL4 function appears to be complex but involves the activities of protein convertase enzymes. Notably, Pcks5 is expressed in the uterus and placenta during implantation in mice (Nie et al 2003, Wong et al 2002). Further, blocking expression of this gene prevents implantation in mice (Nie et al 2005) and normal decidual differentiation of human endometrial cells (Tang et al 2005).…”