Impacts of and interactions between environmental stress and epigenetic programming during early embryo development.

The processes of assisted reproductive technologies (ART) involve a variety of interventions that impact on the oocyte and embryo. Critically, these interventions cause considerable stress and coincide with important imprinting events throughout gametogenesis, fertilisation and early embryonic development. It is now accepted that the IVM and in vitro development of gametes and embryos can perturb the natural course of development to varying degrees of severity. Altered gene expression and, more recently, imprinting disorders relating to ART have become a focused area of research. Although various hypotheses have been put forward, most research has been observational, with little attempt to discover the mechanisms and periods of sensitivity during embryo development that are influenced by the culture conditions following fertilisation. The embryo possesses innate survival factor signalling pathways, yet when an embryo is placed in culture, this signalling in response to in vitro stress becomes critically important in mitigating the effects of stresses caused by the in vitro environment. It is apparent that not all embryos possess this ability to adequately adapt to the stresses experienced in vitro, most probably due to an inadequate oocyte. It is speculated that it is important that embryos use their survival signalling mechanisms to maintain normal epigenetic programming. The seeming redundancy in the function of various survival signalling pathways would support this notion. Any invasion into the natural, highly orchestrated and dynamic process of sexual reproduction could perturb the normal progression of epigenetic programming. Therefore the source of gametes and the subsequent culture conditions of gametes and embryos are critically important and require careful attention. It is the aim of this review to highlight avenues of research to elucidate the effects of stress and the relationship with epigenetic programming. The short- and long-term health and viability of human and animal embryos derived in vitro will also be discussed.