The advent of in vitro fertilization (IVF) in animals and humans implies an extraordinary change in the environment where the beginning of a new organism takes place. In mammals fertilization occurs in the maternal oviduct, where there are unique conditions for guaranteeing the encounter of the gametes and the first stages of development of the embryo and thus its future. During this period a major epigenetic reprogramming takes place that is crucial for the normal fate of the embryo. This epigenetic reprogramming is very vulnerable to changes in environmental conditions such as the ones implied in IVF, including in vitro culture, nutrition, light, temperature, oxygen tension, embryo-maternal signaling, and the general absence of protection against foreign elements that could affect the stability of this process. The objective of this review is to update the impact of the various conditions inherent in the use of IVF on the epigenetic profile and outcomes of mammalian embryos, including superovulation, IVF technique, embryo culture and manipulation and absence of embryo-maternal signaling. It also covers the possible transgenerational inheritance of the epigenetic alterations associated with assisted reproductive technologies (ART), including its phenotypic consequences as is in the case of the large offspring syndrome (LOS). Finally, the important scientific and bioethical implications of the results found in animals are discussed in terms of the ART in humans.
Antes del surgimiento de la epigenética, la relación genes-ambiente era explicado bajo la visión de un "determinismo genético". Ambas concepciones, epigenética y determinismo genético, tienen sus ancestros en los conceptos de epigénesis y preformismo que surgieron en los siglos XVII y XIX 3 . Posteriormente, prevaleció la concepción de que tanto el desarrollo como el fenotipo estaban definidos casi exclusivamente por los genes. A comienzos del siglo XX la Genética era considerada la ciencia de la herencia y la Embriología la del desarrollo 4 . Waddington trató de demostrar que ambas disciplinas estaban estrechamente ligadas entre sí y con la evolución, de manera que la explicación del desarrollo desde el genotipo al fenotipo tendrían que necesariamente integrar el conocimiento de ambas ciencias.En las últimas décadas, sus planteamientos se han retomado en una nueva perspectiva. Actualmente se reconoce el papel fundamental que el ambiente extranuclear, extracelular y social ejerce en la modulación de la actividad genética 5 . Los modelos simples aditivos que sugieren que el fenotipo es la suma de los efectos de los genes y del ambiente, no dan respuesta a la realidad 6 . Se propone que los sistemas genéticos son dinámicos o cibernéticos 7 . Al respecto, investigadores 8 han demostrado cómo el nivel socioeconómico modifica la heredabilidad del coeficiente intelectual (CI) de manera no lineal. Estos autores, a diferencia
The new discoveries, the extraordinary dynamism in human stem cell (SC) research, and the great expectations of the benefi ts in clinical treatment of many diseases are on the edge of unparalleled advances in both: 1) the understanding of basic mechanisms of cell diff erentiation and development and 2) the translation from basic research to new clinical therapies. Human stem cells are obtained from diff erent sources, such as embryo, fetal, and adult tissues, in vitro induction (iPS cells) or transdiff erentiation. The evidence that these cells are pluripotent (or multipotent), meaning they have the ability to diff erentiate into all body tissues or tissues of the same lineage, raises the possibility that they could regenerate diseased or damaged tissue in diseases that until now have had no eff ective treatments. Human stem cell research and therapy raise important bioethical considerations because of the human nature of these cells and their peculiar characteristics. Here we discuss the bioethical aspects of basic human SC research and the conditions necessary for the translation of basic preclinical research into clinical use of SC.
The issue of when the human life begins is a very important subject since it has a signifi cant impact on the decisions that we have to take in relation to human beings in development, particularly human embryos. In this article we discuss some of the more relevant biological evidence supporting the fact that beginning human life begins unquestionably at fertilization and the bioethical consequences.
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