Failure of Parturition in Mice Lacking the Prostaglandin F Receptor-Reference-Cited by-同舟云学术

Failure of Parturition in Mice Lacking the Prostaglandin F Receptor

Published:1997-08 Issue:5326 Volume:277 Page:681-683
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Sugimoto Yukihiko¹²³⁴,Yamasaki Atsushi¹²³⁴,Segi Eri¹²³⁴,Tsuboi Kazuhito¹²³⁴,Aze Yoshiya¹²³⁴,Nishimura Tatsuya¹²³⁴,Oida Hiroji¹²³⁴,Yoshida Nobuaki¹²³⁴,Tanaka Takashi¹²³⁴,Katsuyama Masato¹²³⁴,Hasumoto Ken-yuh¹²³⁴,Murata Takahiko¹²³⁴,Hirata Masakazu¹²³⁴,Ushikubi Fumitaka¹²³⁴,Negishi Manabu¹²³⁴,Ichikawa Atsushi¹²³⁴,Narumiya Shuh¹²³⁴

Affiliation:

1. 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.

2. Y. Aze, T. Nishimura, H. Oida, Fukui Research Institute, Ono Pharmaceutical Company, Limited, Fukui 913, Japan.

3. 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.

4. T. Murata, M. Hirata, F. Ushikubi, S. Narumiya, Department of Pharmacology, Faculty of Medicine, Kyoto University, Kyoto 606, Japan.

Abstract

Mice lacking the gene encoding the receptor for prostaglandin F 2α (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 F 2α interacts with FP in ovarian luteal cells of the pregnant mice to induce luteolysis.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference26 articles.

1. S. Moncada R. J. Flower J. R. Vane in The Pharmacological Basis of Therapeutics A. G. Gilman L. S. Goodman T. W. Rall F. Murad Eds. (McGraw-Hill New York ed. 7 1985) pp. 660–673.

2. Sugimoto Y., et al., J. Biol. Chem. 269, 1356 (1994).

3. A 9.8-kb genomic fragment for FP was subcloned into pBluescript (Stratagene). A 1.3-kb fragment containing the region encoding the NH 2 -terminus to Leu 266 in the sixth transmembrane domain (2) was replaced by LacZ and the neomycin resistance gene ( Neo ) so that the FP-derived Met-Ser residues could be fused to the NH 2 -terminus of β-galactosidase. The MC1-herpes simplex virus thymidine kinase ( HSV-TK ) gene was inserted into the Spe I site at the 3′ end of the homologous region. Two lines of resultant embryonic stem (E14-1) cells injected into C57BL/6 blastocysts gave rise to chimeric offspring which in turn were mated with C57BL/6 females.

4. Ovaries or their sections (10 μm thick) were fixed with glutaraldehyde for 1 hour and stained with X-Gal (5-bromo-4-chloro-3-indoxyl-β- d -galactopyranoside) at 30°C. Sections were then counterstained with eosin.

5. Gonadotropin-synchronized ovary was subjected to RNA isolation for Northern blot analysis or crude membrane preparation for binding assay. A Pst I–Bgl II fragment [690 base pairs (bp)] of FP cDNA (2) was used as an exon 2–specific probe.

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