Opposing actions of prostaglandins and oxytocin determine the onset of murine labor
Open accessAbstract
Prostaglandins (PGs) have been recently proven essential for parturition in mice. To dissect the contributions of the two cyclooxygenase (COX) isoforms to the synthesis of PGs during pregnancy, we have characterized the parturition phenotype of COX-1-deficient mice. We find that mice with targeted disruption of the COX-1 gene have delayed parturition resulting in neonatal death. Results of matings of COX-1-deficient females with COX-1 intact males, and blastocyst transfer of COX-1-deficient or -intact embryos into wild-type foster mothers, proved necessity and sufficiency of maternal COX-1 for the normal onset of labor. COX-1 expression is induced in gravid murine uterus and by in situ hybridization; this induction is localized to the decidua. Measurement of uterine PGs further confirmed that COX-1 accounted for the majority of PGF2α production. To evaluate the interaction of PGs with oxytocin during murine labor, we generated mice deficient in both oxytocin and COX-1. Surprisingly, the combined oxytocin and COX-1-deficient mice initiated labor at the normal time. COX-1-deficient mice demonstrated impaired luteolysis, as evidenced by elevated serum progesterone concentration and ovarian histology late in gestation, and delayed induction of uterine oxytocin receptors. In contrast, simultaneous oxytocin and COX-1 deficiency restored the normal onset of labor by allowing luteolysis in the absence of elevated PGF2α production. These findings demonstrate that COX-1 is essential for normal labor in the mouse, with a critical function being to overcome the luteotrophic action of oxytocin in late gestation.
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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 [34]
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“For example, prostaglandins (PGs) are central components of labour in both humans and mice [11].”
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- Authors
- Gross, G. A., Imamura, T., Luedke, C., Vogt, S. K., Olson, L. M., Nelson, D. M., Sadovsky, Y., & Muglia, L. J.
- Affiliations
- Boston Children's Hospital (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1998-09-29
- Volume
- 95
- Issue
- 20
- Pages
- 11875-11879
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC21733
- OpenAlex
- W2077608143
- Cited by
- 238
- References
- 26
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 7 · 2022: 5 · 2021: 8 · 2020: 3 · 2019: 8 · 2018: 5 · 2017: 7 · 2016: 3 · 2015: 5 · 2014: 8 · 2013: 9 · 2012: 3
- FWCI
- 10.70
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- National Institutes of Health (5k08dk002270-04, 5p60dk020579-35, 1p30hd033688-01, DK20579, P60-DK-20579)
- National Institute of Diabetes and Digestive and Kidney Diseases (K08DK02270, 2P60-DK-20579, P60-DK-020579)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 33688)
- 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, labor onset, prostaglandins, oxytocin, cyclooxygenase-1, prostaglandin F2alpha, luteolysis, progesterone, decidua, neonatal death, blastocyst transfer
- MeSH terms
- Animals, Corpus Luteum, Embryo Transfer, Female, Isoenzymes, Labor Onset, Male, Membrane Proteins, Ovary, Oxytocin, Phenotype, Pregnancy, Prostaglandin-Endoperoxide Synthases, Prostaglandins, Uterus, Dinoprost, Gene Expression, In Situ Hybridization, Mice, Knockout, Mice, Cyclooxygenase 1
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