. Implantation involves a complex discourse between the embryo and uterus and is a gateway to successful pregnancy. The fundamental feature of this process is the synchronized development of preimplantation embryos to implantation-competent blastocysts and uterine differentiation to the receptive state that result from coordinated integration of various signaling pathways. Burgeoning evidence points toward critical roles of endocannabinoids, a group of bioactive lipid mediators, in embryo-uterine interactions during pregnancy. Our continuing goal is to unravel the genetic and molecular landscape of endocannabinoid signaling that directs preimplantation, implantation and postimplantation events critical to successful pregnancy.Our specific aims are to determine using mouse models: (1) whether endocannabinoid signaling status impacts global gene expression pattern jn preimplantation embryo; (2) whether endocannabinoid signaling coordinates with adrenergic signaling to direct preimplantation development; (3) whether deferral of on-time implantation arising from aberrant endocannabinoid signaling leads to compromised pregnancy outcome; and (4) whether targeted deletion of NAPE-PLD influences anandamide status in the oviduct and uterus to affect early pregnancy events. We will use genetic, molecular, cell biological and physiological approaches to accomplish our goals. The results from the proposed researchwill have profound impact onfemale fertility regulation. Considering womencomprise about 50% of the world population, our research is genuinely and importantly aimed at improving women's reproductive health as it relates to drugs of abuse.