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This chapter considers the susceptibility of the early stages of mammalian development before embryo implantation, and even before fertilization has occurred. Maternal obesity and high body mass index (BMI) are associated with reduced fertility and an increased risk of miscarriage in both natural and assisted pregnancies. The pre-implantation embryo has received significant attention in recent years with respect to environmental effects on short- and long-term gestational development, and health into adulthood. Pre-implantation embryos during either early cleavage or until blastocyst formation are cultured in vitro for in vitro fertilization (IVF) and assisted reproductive technologies (ART) treatments. DNA methylation patterns are extensively remodeled during pre-implantation development, thereby providing a potential window for epigenetic sensitivity to environmental conditions. Maternal nutritional restriction during the periconceptional period leads to adverse developmental programming during fetal and postnatal life in domestic animal models.