COX-2 Function In Rat Ovulation, Implantation And Decidualization

Cyclooxygenase (COX) is a rate-limiting enzyme that produces prostaglandins (PGs) from archidonic acid and exists in two isoforms, COX-1 and COX-2. A previous study showed that COX-2-deficient females are infertile with abnormalities in ovulation, fertilization, implantation and decidualization. However, it was recently shown that the reproductive defects of COX-2-deficient mice mainly depend upon genetic background of the mouse strains. The expression and function of COX-2 in rat reproduction are still unknown. The expression of COX-1 and COX-2 in rat uterus during early pregnancy was examined. There was a low level of COX-1 immunostaining in the luminal epithelium from days 1 to 3 of pregnancy. From days 4 to 5, COX-1 immunostaining reached to a high level in the luminal epithelium. On day 6, COX-1 immunostaining was highly seen in the luminal epithelium and at a basal level in the subluminal stroma at implantation site, whereas a slightly lower level of COX-1 immunostaining was detected in the luminal epithelium at inter-implantation site. On day 7, a low level of COX-1 immunostaining was seen in the luminal epithelium and primary decidua. On days 8 and 9, a low level of COX-1 immunostaining was observed in the whole decidua. There was no detectable COX-2 immunostaining in the uteri from days 1 to 5 of pregnancy. On day 6, COX-2 immunostaining and mRNA were highly seen in the subluminal stroma at implantation site. On days 7, 8 and 9, a highly level of COX-2 immunostaining was seen in primary decidua. We also examined the action of COX-2 in rat ovulation, implantation and decidualization by using two specific inhibitors of COX-2 (nimesulide and niflumic acid). Compared to control, either nimesulide or niflumic acid significantly inhibited the ovulation in the superovulated rats. Although nimesulide had no obvious effects on the number of implantation sites, the weights of implantation sites were significantly reduced in the nimesulide-treated groups. Nimesulide also had an obviously inhibitory effect on decidualization under artificial decidualization. Moreover, nimesulide caused the increase of the gestation period and the reduction of litter size and birth weight compared to controls. Compared to controls, COX-2, mPGES-1, PPAR5, HB-EGF, phospho-STAT3, phosphor-p38, Snail and vimentin expressions were down-regulated in the nimesulide-treated groups. However, COX-1 expression was up-regulated in the nimesulide-treated groups.