Successful embryo implantation requires a coordinated series of steps in which an activated blastocyst interacts with the surrounding uterine epithelium and stroma. Prostaglandins (PG) are essential to embryo implantation, and are important to the localized increase in uterine vascular permeability. Cyclooxygenase is responsible for conversion of arachidonic acid to PGs and exists in two isoforms, COX-1 and COX-2. COX-1 is constitutively expressed, influenced by estrogen and progesterone, and expressed predominantly in the uterine luminal epithelium prior to implantation. COX-1 deficient mice appear to have normal fertility, but reduced inflammatory responses. We examined the role of COX-1 derived PGs during the period of uterine preparation prior to implantation. Figure

figure 1

Figure 1

125I-BSA was injected i.v. into wild type and COX-1(-/-) female mice on day 4 of pregnancy (d1=vag. plug). Mice were saline perfused and killed. Uteri were flushed to check pregnancy and 125I counts were recorded. COX-1(-/-) mice had reduced 125I-BSA and uterine weight, suggesting COX-1 mediated PG production is important in pre-implantation uterine vascular permeability. To evaluate COX-2 compensation in the absence of COX-1, we performed northern and in-situ hybridizations of COX-1(-/-) uteri with COX-2 probes, and administered a selective COX-2 inhibitor to COX-1 null mice. Collectively, our results indicate that PGs produced by COX-1 are important to uterine preparation for implantation, and that there is some alteration in COX-2 regulation in the absence of PG production by COX-1.