The mammalian embryo possesses a great deal of autonomy in early development: embryos can develop to the blastocyst stage when cultured in a solution of salts, amino acids, energy substrates, and a surfactant. Nonetheless, the maternal environment modulates developmental events to improve blastocyst competence for maintenance of pregnancy and to alter characteristics of the resultant offspring. Regulation of preimplantation embryonic development is mediated in part by cell-signaling molecules produced by the endometrium. These molecules, termed embryokines, include insulin-like growth factor 1 (IGF1), colony stimulating factor 2 (CSF2), dickkopf WNT signaling pathway inhibitor 1 (DKK1), and activin A. Some of the variation in fertility between females is likely caused by differences in secretion of specific embryokines by the maternal endometrium. The best example is for DKK1. Gene expression for DKK1 in the endometrium was reduced in lactating cows as compared with nonlactating cows and in heifers that were inherently infertile as compared with heifers that were inherently fertile. Actions of embryokines on the preimplantation embryo have the potential to program long-term changes in fetal development and postnatal phenotype. In the cow, this has been observed for DKK1 (reduced birth weight) and CSF2 (increased postnatal growth). Developmental programming of postnatal phenotype often is characterized by sexual dimorphism. At least in part, sex-dependent effects of maternal environment during the preimplantation period could be due to sex-specific actions of specific embryokines. Thus, for example, actions of CSF2 on the morula- and blastocyst-stage embryo affect trophoblast elongation at d 15 of gestation differently for female embryos than male embryos. Further elucidation of the function of embryokines may lead to novel methods for improving fertility and altering postnatal function.