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Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

2009, Número 1

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Rev Invest Clin 2009; 61 (1)


Mecanismos transgeneracionales en el desarrollo de enfermedades metabólicas

Zambrano E

Idioma: Español
Referencias bibliográficas: 73
Paginas: 41-52
Archivo PDF: 427.74 Kb.


RESUMEN

Estudios epidemiológicos en humanos y con animales de experimentación han demostrado que el ambiente subóptimo intrauterino y durante la lactancia afecta el crecimiento y predispone al individuo al desarrollo de enfermedades en la vida adulta. Una de las características más interesantes de la programación del desarrollo es la evidencia de que las consecuencias adversas del ambiente intrauterino alterado pasa a través de las generaciones. Para obtener el fenotipo transgeneracional es necesario que el ambiente negativo esté en contacto en la vida fetal o neonatal, el fenotipo fisiológico o enfermedad puede ser transmitido a través de la línea germinal sin que las siguientes generaciones hayan sido expuestas directamente al factor ambiental. La hipótesis ha sido bien aceptada gracias a los estudios realizados con animales de experimentación: 1) restricción nutricional o sobrealimentación durante el embarazo y la lactancia; 2) restricción del flujo sanguíneo útero placentario; 3) exposición fetal a concentraciones altas de glucocorticoides, y 4) diabetes materna gestacional experimental. La restricción proteínica materna en la rata adversamente afecta el metabolismo de la glucosa de la segunda generación, los efectos varían de acuerdo al sexo y al periodo de desnutrición. Los estudios con dexametasona a ratas preñadas han demostrado los efectos metabólicos transgeneracionales tanto por la vía materna como la paterna. La primera generación de hembras diabéticas provenientes de ratas F0 tratadas con estreptozotocina durante el embarazo, tienen crías F2 con alteración en el metabolismo de carbohidratos. Los resultados obtenidos sugieren que los mecanismos involucrados en la programación del desarrollo son epigenéticos y no debido a mutaciones en la secuencia de DNA. Muchos individuos en todo el mundo han sufrido desnutrición, estrés, hiperglicemia y otros ambientes negativos durante el embarazo y/o la lactancia. El reto durante este periodo crítico del desarrollo puede inducir la programación inadecuada y adversamente alterar no sólo a la generación F1 sino a las siguientes generaciones. La prevención o tratamiento de estas condiciones ayudaría a minimizar el riesgo de la transmisión de enfermedades metabólicas a futuras generaciones.


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