Is Grease the Word? Part I: Implantation

Abstract

Early in the course of embryo development, the blastocyst must attach to the uterine lining in a process called implantation. Failure of implantation is frustratingly common with assisted reproduction techniques used to treat infertility, and delayed implantation can lead to subsequent problems with the pregnancy (see Dey). Ye et al. found that female mice lacking LPA 3 , one of four G protein-coupled receptors for lysophosphatidic acid, gave birth to litters with less than half the offspring of those of wild-type mice, despite producing normal numbers of blastocysts. LPA 3 mRNA was present in the endometrial epithelium of wild-type mice but not in fertilized or unfertilized eggs; moreover, its abundance in the uterus increased during early pregnancy. Implantation analysis revealed delayed implantation in the LPA 3 -deficient mice, reduced numbers of implanted blastocysts, and abnormal embryo positioning. Embryo transfer studies indicated that these problems with implantation depended on loss of maternal LPA 3 . Similar implantation phenotypes have been observed in mice lacking cytosolic phospholipase A 2α (cPLA 2α ) or mice in which cyclooxygenase (COX) activity was inhibited, which suggests involvement of the cPLA 2α -arachidonic acid-COX-prostaglandin signaling pathway. Indeed, COX2 mRNA abundance, as well as the abundance of prostaglandins E 2 and I (PGE 2 and PGI), were decreased in the uteri of mice lacking LPA 3 . Although administration of exogenous prostaglandins restored normal timing of implantation, it failed to rescue abnormal embryo positioning. The authors conclude that maternal LPA 3 signaling plays a role in embryo implantation and is linked to the prostaglandin biosynthetic pathway. X. Ye, K. Hama, J. J. A. Contos, B. Anliker, A. Inoue, M. K. Skinner, H. Suzuki, T. Amano, G. Kennedy, H. Arai, J. Aoki, J. Chun, LPA3-mediated lysophosphatidic acid signalling in embryo implantation and spacing. Nature 435 , 104-108 (2005). [PubMed] S. K. Dey, Fatty link to fertility. Nature 435 , 34-35 (2005). [PubMed]