MULTIPLE FEMALE REPRODUCTIVE FAILURES IN CYCLOOXYGENASE 2-DEFICIENT MICE

Cyclooxygenase (COX) is the rate-limiting enzyme in the synthesis of p rostaglandins (PGs) and exists in two isoforms, COX-1 and COX-2. In sp ite of long-standing speculation, definitive roles of PGs in various e vents of early pregnancy remain elusive. We demonstrate herein that th e targeted disruption of COX-2, but not COX-1, in mice produces multip le failures in female reproductive processes that include ovulation, f ertilization, implantation, and decidualization. Using multiple approa ches, we conclude that these defects are the direct result of target o rgan-specific COX-2 deficiency but are not the result of deficiency of pituitary gonadotropins or ovarian steroid hormones, or reduced respo nsiveness of the target organs to their respective hormones.