Embryo hatching and outgrowth are the first critical steps on the way to a successful pregnancy. It is generally held that
serine proteases are responsible for this process, although the exact mechanisms of action are not clearly understood. Recently, we described two novel implantation
serine proteinase (ISP) genes that are expressed during the implantation period. The ISP1 gene encodes the embryo-derived
enzyme strypsin, which is necessary for blastocyst hatching in vitro and the initiation of invasion. The ISP2 gene, which encodes a related
tryptase, is expressed in endometrial glands and is regulated by
progesterone during the peri-implantation period. Based on similarities between ISP2 gene expression and that of a
progesterone-regulated lumenal
serine proteinase activity associated with lysis of the zona pellucida, we have suggested that the
strypsin related
protein, ISP2, may encode a
zona lysin
proteinase. As
tryptases naturally assemble to form tetrameric structures, we have hypothesized that ISP1 and ISP2 tetramerize to form
strypsin and lysin, respectively. In this study, we demonstrate that like ISP2, the ISP1 gene is also expressed in endometrial glands and is positively regulated by
progesterone during implantation. Using in situ hybridization of adjacent tissue sections, we show that the ISP1 and ISP2 genes are co-expressed within the endometrial gland. Following evidence that ISP1 and 2 can efficiently form homotetramers and heterotetramers in silico, we suggest that ISP heterotetramers may be also be secreted into the uterine lumen during the implantation period. That the embryonic
hatching enzyme, may also be secreted into the uterine lumen from uterus, may provide insight into the mechanisms of hatching and implantation initiation.