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Fernando Correa, Manuel L Wolfson, Paula Valchi, Julieta Aisemberg, and Ana María Franchi

The endocannabinoid system (eCS), is a complex system, comprising the main endogenous ligands anandamide and 2-arachidonoyl glycerol, the cannabinoid receptors CB1 and CB2 and the biosynthetic and degrading enzymes. Cumulative evidence shows that the eCS plays an important role in reproduction, from egg fertilization to parturition. Therefore, alterations in this system, either by recreation/therapeutic use of cannabis or deregulation of the endogenous cannabinoids, might lead to adverse pregnancy outcomes, including retardation in embryo development, poor blastocyst implantation, inhibition of decidualization, miscarriage and compromised placentation. Nevertheless, the molecular mechanisms by which the eCS participates in different stages of pregnancy remain poorly understood. In this review, we will examine the evidence from animal and human studies to support the role of the eCS in implantation, early-to-late pregnancy and placentation as well as the difficulties of targeting this system for treatment of female infertility.