Uterine Expression of Prostaglandin H₂Synthase in Late Pregnancy and during Parturition in Prostaglandin F Receptor-Deficient Mice¹

Abstract

PG production in uterine tissues is important for many physiological processes in late pregnancy, including parturition. We examined the expression of the PGH2 synthases, cyclooxygenase-1 (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.

Coordinated regulation of fetal and maternal prostaglandins directs successful birth and postnatal adaptation in the mouse

“…Accordingly, PG receptors in the myometrium are regulated to enhance the contractile response and relax the lower uterine segment during parturition (31)(32)(33)(34). Alternatively, Tsuboi et al suggest that COX-1-derived PGs are responsible for luteolysis, whereas COX-2-derived PGs are produced at a later stage of labor and are associated with the final steps of parturition (29). In our studies, COX-2 expression was highest in decidual cells.…”

“…COX-1 is expressed in the uterine luminal epithelium around the fetus, with extension throughout the interimplantation sites. Although COX-1 expression has been described in the mouse decidua (9), we and others (29) have shown that COX-1 is predominantly expressed in the uterine epithelium. Polarized cells secrete PGs apically or basolaterally (30).…”

miR-144 and targets, c-fos and cyclooxygenase-2 (COX2), modulate synthesis of PGE2 in the amnion during pregnancy and labor

“…These observations indicate that AP-1 plays a key role in the inflammation-mediated induction of labor9. COX2 is a highly inducible gene that is expressed at low to undetectable levels in the uterus throughout most of pregnancy, and it is highly up-regulated by proinflammatory cytokines and E 2 at term1011. COX2 catalyzes the production of prostaglandins in the amnion12 and plays a crucial physiological role in the initiation of labor by functioning as a potent activator of uterine contractility13.…”

In vivo Raman spectral analysis of impaired cervical remodeling in a mouse model of delayed parturition

“…1C,D). It was previously thought that Cox-1-derived prostaglandins directly stimulate myometrial contractility or that PGF2α acts on the corpus luteum, leading to subsequent luteolysis, progesterone fall, and uterine activation for labor 61 . The compensatory mechanisms enabling normal uterine contractions in Cox-1 KO mice are not yet fully understood, but support an impaired cervical remodeling hypothesis that was tested in the current study.…”