Prostaglandin-Endoperoxide Synthase 1 Mediates the Timing of Parturition in Mice Despite Unhindered Uterine Contractility.

Herington JL, O'Brien C, Robuck MF, Lei W, Brown N, Slaughter JC, Paria BC, Mahadevan-Jansen A, Reese J
Endocrinology. 2018 159 (1): 490-505

PMID: 29029054 · PMCID: PMC5761592 · DOI:10.1210/en.2017-00647

Cyclooxygenase (COX)-derived prostaglandins stimulate uterine contractions and prepare the cervix for parturition. Prior reports suggest Cox-1 knockout (KO) mice exhibit delayed parturition due to impaired luteolysis, yet the mechanism for late-onset delivery remains unclear. Here, we examined key factors for normal onset of parturition to determine whether any could account for the delayed parturition phenotype. Pregnant Cox-1KO mice did not display altered timing of embryo implantation or postimplantation growth. Although messenger RNAs of contraction-associated proteins (CAPs) were differentially expressed between Cox-1KO and wild-type (WT) myometrium, there were no differences in CAP agonist-induced intracellular calcium release, spontaneous or oxytocin (OT)-induced ex vivo uterine contractility, or in vivo uterine contractile pressure. Delayed parturition in Cox-1KO mice persisted despite exogenous OT treatment. Progesterone (P4) withdrawal, by ovariectomy or administration of the P4-antagonist RU486, diminished the delayed parturition phenotype of Cox-1KO mice. Because antepartum P4 levels do not decline in Cox-1KO females, P4-treated WT mice were examined for the effect of this hormone on in vivo uterine contractility and ex vivo cervical dilation. P4-treated WT mice had delayed parturition but normal uterine contractility. Cervical distensibility was decreased in Cox-1KO mice on the day of expected delivery and reduced in WT mice with long-term P4 treatment. Collectively, these findings show that delayed parturition in Cox-1KO mice is the result of impaired luteolysis and cervical dilation, despite the presence of strong uterine contractions.

Copyright © 2018 Endocrine Society.

MeSH Terms (21)

Abortifacient Agents, Steroidal Animals Cells, Cultured Cervical Ripening Cervix Uteri Cyclooxygenase 1 Female In Vitro Techniques Luteolysis Membrane Proteins Mice, Inbred Strains Mice, Knockout Mifepristone Myometrium Ovariectomy Oxytocics Oxytocin Pregnancy Pregnancy, Prolonged Progesterone Uterine Contraction

Connections (2)

This publication is referenced by other Labnodes entities:

Links