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Science 1 August 1997:
Vol. 277. no. 5326, pp. 681 - 683
DOI: 10.1126/science.277.5326.681
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Reports

Failure of Parturition in Mice Lacking the Prostaglandin F Receptor

Yukihiko Sugimoto, Atsushi Yamasaki, Eri Segi, Kazuhito Tsuboi, Yoshiya Aze, Tatsuya Nishimura, Hiroji Oida, Nobuaki Yoshida, Takashi Tanaka, Masato Katsuyama, Ken-yuh Hasumoto, Takahiko Murata, Masakazu Hirata, Fumitaka Ushikubi, Manabu Negishi, Atsushi Ichikawa, * Shuh Narumiya

Mice lacking the gene encoding the receptor for prostaglandin F2alpha (FP) developed normally but were unable to deliver normal fetuses at term. Although these FP-deficient mice showed no abnormality in the estrous cycle, ovulation, fertilization, or implantation, they did not respond to exogenous oxytocin because of the lack of induction of oxytocin receptor (a proposed triggering event in parturition), and they did not show the normal decline of serum progesterone concentrations that precedes parturition. Ovariectomy at day 19 of pregnancy restored induction of the oxytocin receptor and permitted successful delivery in the FP-deficient mice. These results indicate that parturition is initiated when prostaglandin F2alpha interacts with FP in ovarian luteal cells of the pregnant mice to induce luteolysis.

Y. Sugimoto, A. Yamasaki, E. Segi, K. Tsuboi, M. Katsuyama, K. Hasumoto, M. Negishi, A. Ichikawa, Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Kyoto 606, Japan.
Y. Aze, T. Nishimura, H. Oida, Fukui Research Institute, Ono Pharmaceutical Company, Limited, Fukui 913, Japan.
N. Yoshida and T. Tanaka, Division of Molecular and Cellular Immunology, Research Institute, Osaka Medical Center for Maternal and Child Health, Osaka 590-02, Japan.
T. Murata, M. Hirata, F. Ushikubi, S. Narumiya, Department of Pharmacology, Faculty of Medicine, Kyoto University, Kyoto 606, Japan.
*   To whom correspondence should be addressed.

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Inhibition of cyclooxygenase-2 prevents inflammation-mediated preterm labor in the mouse.
G. Gross, T. Imamura, S. K. Vogt, D. F. Wozniak, D. M. Nelson, Y. Sadovsky, and L. J. Muglia (2000)
Am J Physiol Regulatory Integrative Comp Physiol 278, R1415-R1423
   Abstract »    Full Text »    PDF »
Expression of PGF2{alpha} receptor mRNA in normal, hyperplastic and neoplastic skin.
K. Muller, P. Krieg, F. Marks, and G. Furstenberger (2000)
Carcinogenesis 21, 1063-1066
   Abstract »    Full Text »    PDF »
Levels and Interactions of p27, Cyclin D3, and CDK4 During the Formation and Maintenance of the Corpus Luteum in Mice.
A. Hampl, J. Pachernik, and P. Dvorak (2000)
Biol Reprod 62, 1393-1401
   Abstract »    Full Text »
Unresolved Issues in the Role of Cyclooxygenase-2 in Normal Physiologic Processes and Disease.
P. E. Lipsky, P. Brooks, L. J. Crofford, R. DuBois, D. Graham, L. S. Simon, L. B. A. van de Putte, and S. B. Abramson (2000)
Arch Intern Med 160, 913-920
   Abstract »    Full Text »    PDF »
Gene Knockout Mice in the Study of Parturitions.
G. Gross, T. Imamura, and L. J. Muglia (2000)
Reproductive Sciences 7, 88-95
   Abstract »    PDF »
Uterine Expression of Prostaglandin H2 Synthase in Late Pregnancy and during Parturition in Prostaglandin F Receptor-Deficient Mice.
K. Tsuboi, Y. Sugimoto, A. Iwane, K. Yamamoto, S. Yamamoto, and A. Ichikawa (2000)
Endocrinology 141, 315-324
   Abstract »    Full Text »    PDF »
Role of the Prostaglandin E Receptor Subtype EP1 in Colon Carcinogenesis.
K. Watanabe, T. Kawamori, S. Nakatsugi, T. Ohta, S. Ohuchida, H. Yamamoto, T. Maruyama, K. Kondo, F. Ushikubi, S. Narumiya, et al. (1999)
Cancer Res. 59, 5093-5096
   Abstract »    Full Text »    PDF »
No mutations found in candidate genes for dystocia.
M. Algovik, J. Lagercrantz, M. Westgren, and A. Nordenskjold (1999)
Hum. Reprod. 14, 2451-2454
   Abstract »    Full Text »    PDF »
Maturation of Spontaneous and Agonist-Induced Uterine Contractions in the Peripartum Mouse Uterus.
A. M. Mackler, C. A. Ducsay, J. D. Veldhuis, and S. M. Yellon (1999)
Biol Reprod 61, 873-878
   Abstract »    Full Text »
Anovulation in Cyclooxygenase-2-Deficient Mice Is Restored by Prostaglandin E2 and Interleukin-1{beta}.
B. J. Davis, D. E. Lennard, C. A. Lee, H. F. Tiano, S. G. Morham, W. C. Wetsel, and R. Langenbach (1999)
Endocrinology 140, 2685-2695
   Abstract »    Full Text »
Functional evidence for divergent receptor activation mechanisms of luteotrophic and luteolytic events in the human corpus luteum.
U. Ottander, C. H.B. Leung, and J. I. Olofsson (1999)
Mol. Hum. Reprod. 5, 391-395
   Abstract »    Full Text »    PDF »
Identification of a GABP{alpha}/{beta} Binding Site Involved in the Induction of Oxytocin Receptor Gene Expression in Human Breast Cells. Potentiation by c-Fos/c-Jun.
S. Hoare, J. A. Copland, T. G. Wood, Y.-J. Jeng, M. G. Izban, and M. S. Soloff (1999)
Endocrinology 140, 2268-2279
   Abstract »    Full Text »
Requirement of nuclear factor kappaB for the constitutive expression of nitric oxide synthase-2 and cyclooxygenase-2 in rat trophoblasts.
N. Callejas, M Casado, L Bosca, and P Martin-Sanz (1999)
J. Cell Sci. 112, 3147-3155
   Abstract »    PDF »
Opposing actions of prostaglandins and oxytocin determine the onset of murine labor.
G. A. Gross, T. Imamura, C. Luedke, S. K. Vogt, L. M. Olson, D. M. Nelson, Y. Sadovsky, and L. J. Muglia (1998)
PNAS 95, 11875-11879
   Abstract »    Full Text »    PDF »
Prostaglandin F2{alpha} Stimulates the Raf/MEK1/Mitogen-Activated Protein Kinase Signaling Cascade in Bovine Luteal Cells.
D.-b. Chen, S. D. Westfall, H. W. Fong, M. S. Roberson, and J. S. Davis (1998)
Endocrinology 139, 3876-3885
   Abstract »    Full Text »    PDF »
Cyclooxygenase in biology and disease.
R. N. Dubois, S. B. Abramson, L. Crofford, R. A. Gupta, L. S. Simon, L. B. A. van de putte, and P. E. Lipsky (1998)
FASEB J 12, 1063-1073
   Abstract »    Full Text »
Prostaglandin F2alpha (PGF2alpha ) and the Isoprostane, 8,12-iso-Isoprostane F2alpha -III, Induce Cardiomyocyte Hypertrophy. DIFFERENTIAL ACTIVATION OF DOWNSTREAM SIGNALING PATHWAYS.
P. Kunapuli, J. A. Lawson, J. A. Rokach, J. L. Meinkoth, and G. A. FitzGerald (1998)
J. Biol. Chem. 273, 22442-22452
   Abstract »    Full Text »    PDF »
Induction of Oxytocin Receptor Gene Expression in Rabbit Amnion Cells.
Y.-J. Jeng, S. J. Lolait, and M. S. Soloff (1998)
Endocrinology 139, 3449-3455
   Abstract »    Full Text »    PDF »


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