Pregnancy

Effect of Ubiquitin-Proteasome Pathway on Mouse Blastocyst Implantation and Expression of Matrix Metalloproteinases-2 and -9

Abstract
Previous studies have documented that ubiquitin-related proteins are present in human, baboon, rhesus monkey, cow, sheep, and mouse pregnant uteri, indicating that the ubiquitin-proteasome pathway (UPP) may be involved in the extensive uterine remodeling during mammalian early pregnancy, but there is still no direct evidence. A mouse intrauterine injection model was employed to study the direct effect of the UPP on mouse embryo implantation and its possible mechanisms. On Day 3 of pregnancy, one of the mouse uterine horns was injected with different concentrations of lactacystin, a specific proteasome inhibitor, or anti-ubiquitin antibody, and the other side was used as a control. On Days 5, 6, and 7, the number of implanted embryos was counted and the expression and gelatinolytic activities of matrix metalloproteinases (MMP)-2 and -9 were studied. Results presented here illustrate that injection of lactacystin and anti-ubiquitin antibody significantly inhibited mouse embryo implantation. Further investigations by reverse transcriptase-polymerase chain reaction and gelatin zymography showed that MMP-2 and -9 mRNA expression, as well as the gelatinolytic activity of MMP-9 in the lactacystin-treated uterine horn significantly decreased, while the activity of MMP-2 was not significantly affected. The results obtained from this study, together with previous reports, suggest that the UPP is involved in mouse embryo implantation, and UPP's effect on embryo implantation is achieved at least in part by regulating MMP-2 and -9 mRNA expression and the gelatinolytic activity of MMP-9.

Key words: Pregnancy • Implantation • Uterus

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