We have described two novel implantation
serine proteinase (ISP) genes that are expressed during the implantation period. The ISP1 gene may encode 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. Recently
strypsin has also been found within uterine fluid, suggesting a second potential role in hatching. Consistently, we have discovered that ISP1 is also expressed in the uterine secretory gland at the time of hatching. In this study we demonstrate that both ISP1 and ISP2 are secreted together into the uterine lumen at peri-implantation, and that the appearance of ISP
protein is regulated positively at the transcriptional level by
progesterone and negatively at the posttranscriptional level by
estrogen. This negative regulation by
estrogen may be overridden in pregnancy as ISP
protein expression is restored during oil-induced decidualization. ISP1 and ISP2
proteins are also expressed in proestrous suggesting additional roles in the endometrial cycle.