LPA3-mediated COX-2 Gene Expression and Its Role in Embryo Implantation

Implantation is a process where the blastocyst attaches and invades into the uterine endometrium. Studies have shown that approximately 22% of conceptions fail to implant, emphasizing the importance of implantation in successful pregnancy. Previous research from our laboratory revealed that targeted deletion of a lysophosphatidic acid (LPA) receptor, LPA₃, causes delay in implantation and alters embryo spacing in the uterus. This was attributed to decreased levels of prostaglandins (PGs), and the rate-limiting enzyme for its synthesis called cyclooxygenase-2 (COX-2). Exogenous administration of PGE₂ into LPA₃-deficient females restored on-time implantation, suggesting that LPA-induced COX-2 and subsequent PG production is critical for successful implantation. In order to further study the molecular signaling pathways that regulate implantation, we developed a mouse endometrial epithelial cell line. Our goal is to determine the mechanisms of LPA₃-mediated COX-2 gene expression in embryo implantation in vitro. Demonstrating the timely regulation of the LPA₃-COX2-PG axis and identifying new signaling molecules in the pathway will further our understanding of endometrial receptivity and mammalian reproduction.