Accepted manuscript
LPA3-mediated lysophosphatidic acid signalling in embryo implantation and spacing
Nature (London), Vol.435(7038), pp.104-108
2005
Handle:
https://hdl.handle.net/2376/114761
PMID: 15875025
Abstract
Every successful pregnancy requires proper embryo implantation. Low implantation rate is a major problem during infertility treatments using assisted reproductive technologies. Here we report a newly discovered molecular influence on implantation through the lysophosphatidic acid (LPA) receptor LPA3 (refs 2-4). Targeted deletion of LPA3 in mice resulted in significantly reduced litter size, which could be attributed to delayed implantation and altered embryo spacing. These two events led to delayed embryonic development, hypertrophic placentas shared by multiple embryos and embryonic death. An enzyme demonstrated to influence implantation, cyclooxygenase 2 (COX2) (ref. 5), was downregulated in LPA3-deficient uteri during pre-implantation. Downregulation of COX2 led to reduced levels of prostaglandins E2 and I2 (PGE2 and PGI2), which are critical for implantation. Exogenous administration of PGE2 or carbaprostacyclin (a stable analogue of PGI2) into LPA3-deficient female mice rescued delayed implantation but did not rescue defects in embryo spacing. These data identify LPA3 receptor-mediated signalling as having an influence on implantation, and further indicate linkage between LPA signalling and prostaglandin biosynthesis.
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Details
- Title
- LPA3-mediated lysophosphatidic acid signalling in embryo implantation and spacing
- Creators
- XIAOQIN XIAOQIN YE - Department of Molecular Biology, Helen L. Dorris Child and Adolescent Neuropsychiatric Disorder Institute, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United StatesKotaro HAMA - Graduate School of Pharmaceutical Sciences, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, JapanJunken AOKL - Graduate School of Pharmaceutical Sciences, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, JapanJerold CHUN - Department of Molecular Biology, Helen L. Dorris Child and Adolescent Neuropsychiatric Disorder Institute, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United StatesJames J. A CONTOS - Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109-1024, United StatesBrigitte ANLIKER - Department of Molecular Biology, Helen L. Dorris Child and Adolescent Neuropsychiatric Disorder Institute, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United StatesAsuka INOUE - Graduate School of Pharmaceutical Sciences, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, JapanMichael K SKINNER - Center for Reproductive Biology, School of Molecular Bioscience, Washington State University, Pullman, Washington 99164-4231, United StatesHiroshi SUZUKI - Department of Developmental Medical Technology (Sankyo), Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, JapanTomokazu AMANO - Department of Developmental Medical Technology (Sankyo), Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, JapanGrace KENNEDY - Department of Molecular Biology, Helen L. Dorris Child and Adolescent Neuropsychiatric Disorder Institute, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United StatesHiroyuki ARAL - Graduate School of Pharmaceutical Sciences, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
- Publication Details
- Nature (London), Vol.435(7038), pp.104-108
- Academic Unit
- Biological Sciences, School of
- Publisher
- Nature Publishing; London
- Identifiers
- 99900548066701842
- Language
- English
- Resource Type
- Accepted manuscript