PG production in uterine tissues is important for many physiological processes in late pregnancy, including parturition. We examined the expression of the PGH(2) synthases, cyclooxygenase-l (COX-1) and COX-2, in uterine tissues during late pregnancy, using PGF receptor-deficient (FP-/-) mice. Female FP-/- mice are unable to deliver normal fetuses at term, as they do not undergo luteolysis necessary for parturition. In wild-type mice, COX-1 messenger RNA (mRNA) was expressed in the endometrial epithelium, myometrium, and decidua throughout late pregnancy. The expression of COX-1 mRNA in the endometrial epithelium and myometrium decreased both in wild-type mice undergoing natural parturition and in FP-/- mice undergoing ovariectomy-induced parturition, but expression of COX-1 mRNA was enhanced in FP-/- mice at the expected term. In wild-type mice, COX-2 mRNA was not expressed in the myometrium before parturition, but was markedly induced during parturition. This induction of COX-2 was absent in FP-/- mice at the expected term, but was found during ovariectomy-induced parturition in these mice. Expression of COX-2 proteins was confirmed by immunohistochemical analysis. Thus, in uterine tissues, myometrial expression of COX-2 is closely associated with the occurrence of parturition, but uterine expression of COX-1 is induced much earlier and kept at a high level until parturition occurs. These results suggest that COX-1-derived PGs are responsible for the induction of luteolysis, and that COX-2-derived PGs play a role in the final pathway of parturition.
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