Opposing actions of prostaglandins and oxytocin determine the onset of murine labor

Gil A. Gross, Takuji Imamura, Christina Luedke, Sherri K. Vogt, Lisa M. Olson, D. Michael Nelson, Yoel Sadovsky, Louis J. Muglia

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204 Scopus citations

Abstract

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-l- 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-I 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.

Original languageEnglish
Pages (from-to)11875-11879
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number20
DOIs
StatePublished - Sep 29 1998

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