Effect of UPP on the expression of VEGF and its receptors in mouse uterus during peri-implantation

On day 3 of gestation, one uterine horn of fe-male pregnant mouse was injected intraluminally with 5 mL 0.1 mg/mL lactacystin, a specific inhibitor of ubiquitin-pro- teasome pathway (UPP), while the contralateral horn served as control. Animals were sacrificed by cervical dislocation on day 5, 6, 7 of gestation, respectively. Then the number of implanted embryos in each uterine horn was calculated, and the expression of VEGF and its receptors was examined. The data showed that the number of implanted embryos was decreased significantly after treatment with lactacystin. The results of RT-PCR and Western blot indicated that expres-sion of VEGF and its receptors at mRNA and protein levels was significantly decreased in the treated uterus, meanwhile, the expression of HIF-1a (the a subunit of HIF, a transcrip-tional factor of VEGF) was reduced at both mRNA and pro-tein levels. These data suggested that the effect of UPP on VEGF expression was realized through regulating HIF-1a expression. In addition, UPP is likely to take part in the modulation of VEGF receptors expression. These changes may be one of the reasons for the reduction of implanted embryos.