The early embryo and periconceptional period is a window during which environmental factors may cause permanent change in the pattern and characteristics of development leading to risk of adult onset disease. This has now been demonstrated across small and large animal models and also in the human. Most evidence of periconceptional ‘programming’ has emerged from maternal nutritional models but also otherin vivoandin vitroconditions including assisted reproductive treatments, show consistent outcomes. This short review first reports on the range of environmentalin vivoandin vitropericonceptional models and resulting long-term outcomes. Second, it uses the rodent maternal low protein diet model restricted to the preimplantation period and considers the stepwise maternal-embryonic dialogue that comprises the induction of programming. This dialogue leads to cellular and epigenetic responses by the embryo, mainly identified in the extra-embryonic cell lineages, and underpins an apparently permanent change in the growth trajectory during pregnancy and associates with increased cardiometabolic and behavioural disease in adulthood. We recognize the important advice of David Barker some years ago to investigate the sensitivity of the early embryo to developmental programming, an insight for which we are grateful.
Periconceptional environment may influence embryo development, ultimately affecting adult health. Here, we review the rodent model of maternal low-protein diet specifically during the preimplantation period (Emb-LPD) with normal nutrition during subsequent gestation and postnatally. This model, studied mainly in the mouse, leads to cardiovascular, metabolic and behavioural disease in adult offspring, with females more susceptible. We evaluate the sequence of events from diet administration that may lead to adult disease. Emb-LPD changes maternal serum and/or uterine fluid metabolite composition, notably with reduced insulin and branched-chain amino acids. This is sensed by blastocysts through reduced mammalian target of rapamycin complex 1 signalling. Embryos respond by permanently changing the pattern of development of their extra-embryonic lineages, trophectoderm and primitive endoderm, to enhance maternal nutrient retrieval during subsequent gestation. These compensatory changes include stimulation in proliferation, endocytosis and cellular motility, and epigenetic mechanisms underlying them are being identified. Collectively, these responses act to protect fetal growth and likely contribute to offspring competitive fitness. However, the resulting growth adversely affects long-term health because perinatal weight positively correlates with adult disease risk. We argue that periconception environmental responses reflect developmental plasticity and ‘decisions’ made by embryos to optimise their own development, but with lasting consequences.
IGF1 plays an important role in bovine follicular growth, acquisition of oocyte competence and embryo viability. Current data also indicate a critical role for IGF1 in both the ovarian response and the embryo yield following the superovulatory treatments. IGF1 can have either positive or negative effects on embryo viability which is related to the concentration of IGF1 induced by superovulation treatment. These effects impact either on oocyte competence or directly on the embryo. Concentrations in the physiological range appear to result in the production of higher quality embryos, mainly due to the mitogenic and the anti-apoptotic activities of IGF1. However, high superovulatory responses are associated with decreased embryo viability and a concomitant increase in apoptosis. Studies in mice suggest that this increase in apoptosis is related to the downregulation of the IGF1 receptor in the embryo associated with high IGF1 concentrations. Strategies capable of controlling the IGF1 concentrations could be one approach to improve superovulation responses. A range of possible approaches for research within the IGF system in gonadotrophin-stimulated cattle is discussed in this review, including the possible use of superovulated female cattle as an alternative animal experimental model for research on reproductive disorders in humans associated with abnormal IGF1 concentrations.