Embryonic hatching enzyme strypsin/ISP1 is expressed with ISP2 in endometrial glands during implantation.
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.
O'Sullivan
Colleen M
CM
Department of Biochemistry and Molecular Biology, Southern Alberta Cancer Research Centre, University of Calgary, Alberta, Canada.
Liu
Shi Ying
SY
Karpinka
J Bradley
JB
Rancourt
Derrick E
DE
D000818:Animals; D001755:Blastocyst; D010064:Embryo Implantation; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D017403:In Situ Hybridization; D051379:Mice / Q000196:embryology; D011374:Progesterone / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000096:biosynthesis*
D011374:Progesterone; C436409:Prss29 protein, mouse; D012697:Serine Endopeptidases; C048419:strypsin