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.
Up to the year 1975, neonatal care in our unit consisted of: pediatricians and nurses without specialization in neonatology; equipment basically limited to incubators; and treatment of premature infants and neonates with respiratory problems reduced to: (1) temperature control, (2) prevention of infection, (3) careful feeding and fluid administration, (4) oxygen therapy based on clinical appearance of cyanosis, and (5) correction of acidosis with NaHCO3.
See table in the PDF file
In 1976, a plan for introducing intensive care was begun.
puc.cl E n la medicina del siglo 21 existe la esperanza de que el avance en la investigación y uso clínico de la células madre (CM) produzca un progreso extraordinario en el tratamiento de enfermedades incurables o en que éste es complejo e insuficiente. El trasplante con CM pretende resolver la patología involucrada mediante la regeneraciónde los tejidos dañados. Enfermedades neurodegenerativas como el Alzheimer (EA), el Parkinson (EP) y la esclerosis lateral amiotrófica (ELA) y otras como la diabetes, cáncer, infarto cardíaco y enfermedades inmunológicas están en la primera línea de ésta expectativa 1 . Existen varios tipos de CM, todas caracterizadas por su capacidad de auto regeneración, potencial de diferenciación y de regenerar tejidos 1 . Se diferencian por su origen y el diverso grado que tienen en las características mencionadas.
Células madre embrionarias (pluripotentes)
(CME)Fueron descubiertas en 1981 por Evansy Martin que, lograron aislar y cultivar in vitro las células pluripotenciales del macizo celular interno del blastocisto de ratón 2,3 . Significó un hito histórico para la comprensión del desarrollo de la homeostasis tisular y de la medicina regenerativa (MR). Se distinguen por su capacidad de autoreplicarse indefinidamente manteniendo su carácter pluripotencial pudiéndose diferenciar en las tres capas embrionarias de las cuales se desarrollan todos los tejidos del organismo. Su capacidad regenerativa ha sido probada en estudios preclínicos in vitro y en animales. El traspaso a estudios clínicos no ha podido concretarse por problemas de seguridad no resueltos como es el caso de producción de tumores. A esto se agrega la grave objeción ética
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