@article{66f99d2981af451eb8b62d1e95bc0654,
title = "LPA3-mediated lysophosphatidic acid signalling in embryo implantation and spacing",
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 preimplantation. Downregulation of COX2 led to reduced levels of prostaglandins E2 and I2 (PGE2 and PGI 2), 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.",
author = "Xiaoqin Ye and Kotaro Hama and Contos, {James J.A.} and Brigitte Anliker and Asuka Inoue and Skinner, {Michael K.} and Hiroshi Suzuki and Tomokazu Amano and Grace Kennedy and Hiroyuki Arai and Junken Aoki and Jerold Chun",
note = "Funding Information: Acknowledgements We thank F. Liu, S. Kupriyanov, R. Rivera, D. Herr, E. Nilsson, M. Murakami, Y. Kita, B. C. Paria, C. Akita, S. Carlson and Q. Chen for technical assistance and suggestions. This work was supported by grants from the National Institute of Mental Health to J.C. and J.J.A.C., the National Institute of Health to M.K.S, Swiss National Science Foundation to B.A., and Program for Promotion of Fundamental Studies in Health Sciences of the Pharmaceuticals and Medical Devices Agency (PMDA) and grants-in-aid from the Ministry of Education, Science, Culture and Sports for the 21st Century Center of Excellence Program, Japan, to H.S., J.A and H.A. Funding Information: Acknowledgements We thank W. Qian and C. Yang for technical assistance; M. Yanagisawa for providing the Tie2-Cre transgenic mice; Y. Furuta for providing the Efnb2 construct for RNA in situ hybridization; and F. Petit for the COUP-TFII minigene construct. We also thank L.-Y. Yu-Lee and H. J. Bellen for discussions and critical reading of the manuscript. This work was supported by NIH grants to S.Y.T. and M.-J.T.",
year = "2005",
month = may,
day = "5",
doi = "10.1038/nature03505",
language = "English",
volume = "435",
pages = "104--108",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7038",
}