Coordinated regulation of fetal and maternal prostaglandins directs successful birth and postnatal adaptation in the mouse
Year: 2000
Type: article
Abstract: 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.
Authors: Jeff Reese, Bibhash C. Paria, Naoko Brown, Xuemei Zhao, Jason D. Morrow, Sudhansu K. Dey
Language: English
Subfield: Pharmacology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: National Institutes of Health, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences, National Institute of Child Health and Human Development, National Center for Research Resources, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Research Center for Pharmacology and Drug Toxicology, SUSTAINED DEVELOPMENT OF CLINICIAN RESEARCHERS, ASPECTS OF BLASTOCYST IMPLANTATION, Research Center for Pharmacology & Drug Toxicology, NEUREGULIN-MEDIATED CELL SIGNALING DURING IMPLANTATION, G510208870, Kansas Intellectual and Developmental Disabilities Research Center (KIDDRC), Biochemistry and Pharmacology of D2/E2 Isoprostanes, G9000057978, G9000076365, G9000137775
OpenAlex ID: W1983003192