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

Reese J, Paria BC, Brown N, Zhao X, Morrow JD, Dey SK
Proc Natl Acad Sci U S A. 2000 97 (17): 9759-64

PMID: 10944235 · PMCID: PMC16938 · DOI:10.1073/pnas.97.17.9759

Cyclooxygenase (COX)-derived prostaglandins (PGs) regulate numerous maternal-fetal interactions during pregnancy. PGs stimulate uterine contractions and prepare the cervix for parturition, whereas in the fetus, PGs maintain patency of the ductus arteriosus (DA), a vascular shunt that transmits oxygenated placental blood to the fetal systemic circulation. However, the origin and site of action of these PGs remain undefined. To address this, we analyzed mice lacking COX-1 (null mutation) or COX-2 (pharmacologic inhibition) or pups with a double null mutation. Our results show that COX-1 in the uterine epithelium is the major source of PGs during labor and that COX-1(-/-) females experience parturition failure that is reversible by exogenous PGs. Using embryo transfer experiments, we also show that successful delivery occurs in COX-1(-/-) recipient mothers carrying wild-type pups, establishing the sufficiency of fetal PGs for parturition. Although patency of the DA is PG dependent, neither COX-1 nor COX-2 expression was detected in the fetal or postnatal DA, and offspring with a double null mutation died shortly after birth with open DAs. These results suggest that DA patency depends on circulating PGs acting on specific PG receptors within the DA. Collectively, these findings demonstrate the coordinated regulation of fetal and maternal PGs at the time of birth but raise concern regarding the use of selective COX inhibitors for the management of preterm labor.

MeSH Terms (25)

Adaptation, Physiological Animals Animals, Newborn Cyclooxygenase 1 Cyclooxygenase 2 Cyclooxygenase 2 Inhibitors Cyclooxygenase Inhibitors Ductus Arteriosus, Patent Embryo Transfer Female Fetal Diseases Fetus Gene Deletion Gene Expression Regulation, Enzymologic Gestational Age In Situ Hybridization Isoenzymes Labor, Obstetric Membrane Proteins Mice Pregnancy Prostaglandin-Endoperoxide Synthases Prostaglandins RNA, Messenger Uterus

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