Characterization of secretory leukocyte protease inhibitor as an inhibitor of implantation serine proteinases

Abstract

We have recently identified and characterized two implantation serine proteinase genes, ISP1 and ISP2, which give rise to a dimeric proteinase, ISP that facilitates embryo invasion during peri-implantation period. As many proteinases have cognate serpins that regulate their proteolytic activity, we have been investigating anti-tryptases, expressed during this window of implantation. Here, we report the differential expression of secretory leukocyte protease inhibitor (SLPI) in uterine endometrium around the implantation period. The co-localization of SLPI and ISP suggests the possibility that SLPI is an ISP serpin and that expression of SLPI may lead to a reduction in ISP activity. The expression of SLPI is down regulated during the window of embryo-uterine receptivity. Our results are consistent with a model suggesting that the drop in SLPI expression may help to refine the opening of the window of implantation, by allowing the proteolytic activity of embryo invasive serine proteinases such as the ISPs.

The common marmoset genome provides insight into primate biology and evolution

“…For example, ADAM6, with a role in fertility 33,34 , was lost in marmoset, while ISP2, involved in embryo implantation 35 , has been duplicated twice. KLK2/3, duplicated in the Catarrhine ancestor 36 and involved in reproductive physiology 33 is non-functional in marmoset.…”

Expression of rat uterine serine proteinases homologous to mouse implantation serine proteinase 2

“…This indicates that ISP may have an important role in the initiation of implantation. Recently, Sharma et al (2008) have characterized secretory leukocyte protease inhibitor as an ISP serpin, the expression of which may lead to a reduction in ISP activity. However, the physiological functions of ISPs during the implantation process, or how they participate in the mechanism of implantation, are still not fully understood.…”