Expression of COX-1 and COX-2 in the endometrium of cyclic, pregnant and in a model of pseudopregnant rats and their regulation by sex steroids

Abstract

BackgroundCyclooxygenases (COXs) are the rate limiting enzymes in the process of prostaglandins (PGs) synthesis, which are critical regulators of a number of reproductive processes, including ovulation, implantation, decidualization and parturition. The aim of the present study was to investigate the expression and regulation of COX-1 and COX-2 and levels of prostaglandins during rat pregnancy, in a model of pseudopregnancy and estrous cycle.MethodsUteri were collected from the cyclic rats on each day of estrous cycle, after every two days for pregnant (days 2 to 22) and pseudopregnant rats (days 1 to 9). In vitro primary endometrial stromal cells were cultured in the presence of steroid hormones and their respective inhibitors for the possible modulation of COX-1 and COX-2. Endometrial protein extracts were used for western blot analysis and tissue sections were prepared for protein localization using immunofluorescence. Measurements of PGF2alpha and PGE2 metabolites in serum were performed by enzyme immunoassay (EIA).ResultsCOX-1 expression was found to be elevated during implantation and parturition, however, the levels of COX-1 decreased during decidualization periods. COX-2 was detected during early pregnancy from day 2 to 5, increased during decidual regression, and was also expressed at the time of parturition. COX-2 protein expression was found to be increased at estrus phase in cyclic rats. Both enzymes were found to be modulated in the endometrium of pseudopregnant rats, suggesting that they are regulated by 17beta-estradiol and progesterone. A significant increase in PGE2 metabolite levels was observed on day 10, 12 and 14 of pregnancy. However, an increase in PGF2alpha metabolite levels was observed only on day 14. The concentration of both these metabolites changed during pseudopregnancy and maximum levels were observed at day 7. Significant increase in PGE2 metabolite was observed at proestrus phase, on the other hand, PGF2alpha metabolite was significantly increased at proestrus and metestrus phase. COX-2 protein was regulated by 17beta-estradiol in cultured endometrial stromal cells which was blocked in the presence of ICI-182,780.ConclusionsTaken together, these results suggest that COX-1 and COX-2 could be differentially regulated by steroid hormones and might be the key factors involved in embryo implantation, decidualization, decidua basalis regression and parturition in rats.

Bridging endometrial receptivity and implantation: network of hormones, cytokines, and growth factors

“…This expression pattern suggests that COX-2 expression during the adhesion phase is critical for implantation (Chakraborty et al 1996). Recently, we have reported that COX-2 expression is regulated by steroid hormones that play a crucial role in embryo implantation and decidualization through PG synthesis (St-Louis et al 2010). Extensive research in past years provides crucial evidence confirming the role of PGs in implantation process.…”

Endometrial changes induced by prostaglandin E2 and EP4 receptor agonist in albino rats

“…Furthermore, many reports on the implication of PGE2 during the implantation window exist [17,18]. However, according to the available literature the impact of PGE2 or its receptor agonists on selected components of the endometrial extracellular matrix namely collagen I, GAGs, HA, and CD44 was not a subject of investigation.…”

“…Large-scale evidence suggests that prostaglandins (PGs), especially prostaglandin E2 (PGE2), are important modulators of events at the site of implantation in laboratory rodents [16][17][18]. PGs induce decidualization when instilled into a rat uterus primed for implantation [19][20][21].…”

Anandamide restricts uterine stromal differentiation and is critical for complete decidualization

“…Thus, one of the causes of implantation and decidualization failure in COX-2 deficient mice is the deregulation of vascular events. The attenuation of uterine angiogenesis in these mice is primarily the result of defective VEGF signaling rather than angiopoietin system (St-Louis et al, 2010).…”