Cytosolic phospholipase A2α is crucial for ‘on-time’ embryo implantation that directs subsequent development

Abstract

Cytosolic phospholipase A2alpha (cPLA2alpha) 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 (cPLA2alpha) 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, cPLA2alpha 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 cPLA2alpha-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.