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La alteración de la metilación de las histonas en el desarrollo de los espermatozoides perjudica la salud de la
Keith Siklenka1, Serap Erkek2, Maren Godmann3
1Department of Pharmacology and Therapeutics, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
Science (New York, N.Y.)
|October 10, 2015
Resumen
La transmisión epigenética paterna puede afectar el desarrollo de la descendencia. La sobreexpresión de la histona demetilasa KDM1A en el esperma causó defectos de salud transgeneracionales, destacando la epigenética del esperma en la herencia.
Área de la Ciencia:
- La epigenética
- Biología del desarrollo
- Ciencias de la reproducción
Sus antecedentes:
- Los factores paternos influyen en la salud y el desarrollo de la descendencia.
- Los mecanismos de la herencia epigenética paterna no se comprenden completamente.
- El papel de los nucleosomas del esperma en la herencia epigenética no está claro.
Objetivo del estudio:
- Investigar el papel de la histona demetilasa KDM1A en la transmisión epigenética paterna.
- Determinar si la actividad de KDM1A en el esperma afecta el desarrollo y la supervivencia de la descendencia.
- Para explorar los efectos transgeneracionales de la epigenética alterada del esperma.
Principales métodos:
- Se generaron ratones transgénicos con sobreexpresión de KDM1A durante la espermatogénesis.
- Las modificaciones histónicas analizadas (dimetilación de H3K4) en el esperma.
- Evaluar el desarrollo de la descendencia, la supervivencia y los perfiles de ARN.
- Se ha examinado la metilación del ADN en regiones ricas en CpG.
Principales resultados:
- La sobreexpresión de KDM1A en el esperma redujo la dimetilación de H3K4.
- La descendencia de padres con sobreexpresión de KDM1A mostró un deterioro en el desarrollo y la supervivencia.
- Estos defectos fueron transgeneracionales y persistieron sin expresión de la línea germinal de KDM1A.
- Se observaron perfiles alterados de ARN en el esperma y la descendencia.
- No se detectaron cambios en la metilación del ADN en regiones ricas en CpG.
Conclusiones:
- La actividad de la histona demetilasa en el esperma en desarrollo puede iniciar la herencia epigenética de defectos de desarrollo.
- La herencia epigenética puede ocurrir sin alteraciones en la metilación del ADN en los sitios de CpG.
- La epigenética del esperma, influenciada por factores como KDM1A, juega un papel crítico en los resultados de salud transgeneracionales.
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