1. 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, USA
2. Graduate School of Pharmaceutical Sciences, and
3. Department of Developmental Medical Technology (Sankyo), Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
4. Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109-1024, USA
5. Center for Reproductive Biology, School of Molecular Bioscience, Washington State University, Pullman, Washington 99164-4231, USA
6. National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan
7. *These authors contributed equally to this work

Correspondence to: Jerold Chun¹ Correspondence and requests for materials should be addressed to J.C. (Email: jchun@scripps.edu).

Abstract

Every successful pregnancy requires proper embryo implantation. Low implantation rate is a major problem during infertility treatments using assisted reproductive technologies¹. 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 implantation¹. 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.

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.