Abstract In mammals, the birth of viable and healthy progeny involves a continuum of complex biological processes and several checkpoints (or hurdles) that have to be passed successfully. In terms of contribution to pregnancy, the male differs from the female, since the mother not only produces gametes (oocytes), but she also hosts the whole gestation, mainly in the uterus. The uterus is covered with endometrium, a tissue layer endowed with unique features that initiates cellular and molecular interactions with the embryo during implantation, making this step a critical checkpoint of pregnancy. Current data have demonstrated that congenital anomalies, acquired diseases or perturbations of adult maternal physiology before and during reproductive life (e.g. stress, nutrition; endocrine disruptors, infection) can affect endometrial function in a permanent or transient manner. Distinct endometrial responses can also be elicited by embryos presenting distinct post-implantation fates. Indeed biological functions (e.g. metabolism and immune function), molecular pathways (e.g. oxidative phosphorylation) and individual genes (e.g. SOCS3) were affected in bovine endometrium facing various types of embryos produced by artificial insemination, in vitro fertilization or somatic cell nuclear transfer. These findings have led to the concept that endometrium is an early biosensor of embryo developmental potential, which is useful for the prediction of pregnancy issues. This biological property, first demonstrated in cattle, has been recently applied to human species, since the expression of immune genes in decidualized stroma cells was reported to differ in cultured endometrial cells incubated with developing or non-developing embryos. Hence, mammalian endometrium appears as a dynamic and reactive tissue whose physiology can be negatively affected by environmental factors or types of embryos. This compromised or suboptimal endometrial quality can subtly or deeply affect embryo development before implantation, with visible and sometimes severe consequences for the placentation process and fetal development, as well as pregnancy outcome and the long-term health of the offspring.