LPA3-mediated lysophosphatidic acid signalling in embryo implantation and spacing

Xiaoqin Ye, Kotaro Hama, James J.A. Contos, Brigitte Anliker, Asuka Inoue, Michael K. Skinner, Hiroshi Suzuki, Tomokazu Amano, Grace Kennedy, Hiroyuki Arai, Junken Aoki, Jerold Chun

Research output: Contribution to journalArticlepeer-review

398 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)104-108
Number of pages5
JournalNature
Volume435
Issue number7038
DOIs
Publication statusPublished - 2005 May 5
Externally publishedYes

ASJC Scopus subject areas

  • General

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