Jeff Reese
Last active: 1/7/2021

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

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