Cytosolic phospholipase A2α deficiency is crucial for 'on-time' embryo implantation that directs subsequent development

Cytosolic phospholipase A 2 α (cPLA 2 α) is a major provider of arachidonic acid (AA) for the cyclooxygenase (COX) system for the biosynthesis of prostaglandins (PGs). Female mice with the null mutation for Pla2g4a (cPLA 2 α) produce small litters and often exhibit pregnancy failures, although the cause(s) of these defects remains elusive. We show that the initiation of implantation is temporarily deferred in Pla2g4a –/– mice, shifting the normal ‘window’ of implantation and leading to retarded feto-placental development without apparent defects in decidual growth. Furthermore, cPLA 2 α deficiency results in aberrant uterine spacing of embryos. The deferred implantation and deranged gestational development in Pla2g4a –/– mice were significantly improved by exogenous PG administration. The results provide evidence that cPLA 2 α-derived AA is important for PG synthesis required for on-time implantation. This study in Pla2g4a –/– mice, together with the results of differential blastocyst transfers in wild-type mice provides the first evidence for a novel concept that a short delay in the initial attachment reaction creates a ripple effect propagating developmental anomalies during the subsequent course of pregnancy.