Prostaglandin-Endoperoxide Synthase 1 Mediates the Timing of Parturition in Mice Despite Unhindered Uterine Contractility
Open accessAbstract
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 (P 4 ) withdrawal, by ovariectomy or administration of the P 4 -antagonist RU486, diminished the delayed parturition phenotype of Cox-1KO mice.Because antepartum P 4 levels do not decline in Cox-1KO females, P 4 -treated WT mice were examined for the effect of this hormone on in vivo uterine contractility and ex vivo cervical dilation.P 4 -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 P 4 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.(Endocrinology 159: 490-505, 2018) P regnancy duration and the onset of birth (parturition) are tightly regulated events (1-3).One of the early factors known to influence the timing of labor is the timing of embryo implantation.Delayed or poor embryo implantation can result in mistiming of parturition, in part due to delayed or poor in utero embryonic development and maturation (4-6).Multiple-gestation pregnancies also contribute to the timing of parturition: Larger numbers of offspring prompt an earlier delivery, whereas few offspring in polytocous species are associated with prolonged gestation (7, 8).A larger-than-normal number of offspring triggers early-onset parturition due to premature stretch of uterine myometrial cells, activating the uterus to contract.The fetus and placenta also emit molecular signals that control the length of pregnancy and trigger the onset of labor (1, 9-11).
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The prolonged gestation interval observed in the ERKdko females was reminiscent of phenotype described for the cyclooxygenase 1 (PGHS1/COX1) knockout animal.
“First, the prolonged gestation interval observed in the ERKdko females was reminiscent of phenotype described for the cyclooxygenase 1 (PGHS1/COX1) knockout animal34–39.”
From Conditional loss of ERK1 and ERK2 results in abnormal placentation and delayed parturition in the mouse (2019) · cites this paper as [39]
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- Authors
- Herington, J. L., O’Brien, C., Robuck, M. F., Lei, W., Brown, N., Slaughter, J. C., Paria, B. C., Mahadevan-Jansen, A., & Reese, J.
- Affiliations
- Vanderbilt University Medical Center (US)
- Vanderbilt University (US)
- Soochow University (CN)
- Corresponding author
- Herington, Jennifer L
- ORCID
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2017-09-29
- Volume
- 159
- Issue
- 1
- Pages
- 490-505
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC5761592
- OpenAlex
- W2759334075
- Cited by
- 18
- References
- 96
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 3 · 2018: 1
- FWCI
- 1.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrinology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Vanderbilt University
- Vanderbilt University Medical Center
- Georgia Clinical and Translational Science Alliance (KL2TR000446)
- National Institutes of Health (KL2TR000446)
- National Institute of General Medical Sciences (R01GM118361)
- National Institute of Child Health and Human Development
- National Center for Advancing Translational Sciences
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD081121, R21HD088830, R01HD081121, R21HD080148)
- Topics
- Health Sciences › Medicine › Epidemiology › Preterm Birth and Chorioamnionitis
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Life Sciences › Agricultural and Biological Sciences › Agronomy and Crop Science › Reproductive Physiology in Livestock
- Keywords
- childbirth, cyclooxygenase-1, luteolysis, progesterone withdrawal, uterine contractility, cervical dilatation, oxytocin, labor onset, gestation length, embryo implantation, myometrium, RU486
- MeSH terms
- Abortifacient Agents, Steroidal, Animals, Cells, Cultured, Cervix Uteri, Luteolysis, Female, Membrane Proteins, Mice, Inbred Strains, Myometrium, Ovariectomy, Oxytocics, Oxytocin, Pregnancy, Pregnancy, Prolonged, Progesterone, Uterine Contraction, Mifepristone, Mice, Knockout, Cervical Ripening, Cyclooxygenase 1, In Vitro Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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