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Inherencia materna de la intolerancia a la glucosa a través de la insuficiencia de los ovocitos TET3
Bin Chen1,2,3, Ya-Rui Du3, Hong Zhu4,5
1Key Laboratory of Reproductive Genetics (Ministry of Education), Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Nature
|May 18, 2022
Resumen
La hiperglucemia gestacional materna puede aumentar la descendencia
Área de la Ciencia:
- Biología de la reproducción
- Endocrinología
- La epigenética
Sus antecedentes:
- La diabetes mellitus afecta a muchas mujeres en edad reproductiva.
- La diabetes gestacional tiene consecuencias a largo plazo para la descendencia.
- El impacto de la diabetes gestacional en el riesgo de enfermedad de la descendencia adulta es poco estudiado.
Objetivo del estudio:
- Investigar el vínculo entre la diabetes gestacional y la intolerancia a la glucosa de la descendencia.
- Explorar el papel de la dioxigenasa TET3 en la mediación de este efecto materno.
- Identificar las posibles intervenciones previas a la concepción.
Principales métodos:
- Se utilizó un modelo de ratón de hiperglucemia (ratones HG) y muestras humanas.
- Expresión evaluada de la dioxigenasa TET3 en los ovocitos.
- Se analizaron los patrones de metilación del ADN de los genes de secreción de insulina.
- Se examinó la homeostasis de la glucosa y los marcadores epigenéticos en la descendencia.
Principales resultados:
- Reducción de la expresión de TET3 en ovocitos de ratones HG y humanos con diabetes.
- La insuficiencia de TET3 de los ovocitos conduce a la hipermetilación de los genes de insulina paterna (por ejemplo, Gck).
- Este cambio epigenético persiste, causando alteraciones en la homeostasis de la glucosa y defectos en la secreción de insulina en la descendencia.
- La deleción materna de Tet3 en ratones recapitula estos efectos, mientras que el mRNA Tet3 exógeno los mejora.
Conclusiones:
- La hiperglucemia gestacional predispone a la descendencia a la intolerancia a la glucosa a través de la insuficiencia TET3 durante el desarrollo de los ovocitos.
- Este mecanismo epigenético, en lugar de la perturbación directa del ovocito, subyace al efecto materno.
- Las intervenciones previas a la concepción dirigidas a la salud materna pueden proteger la salud metabólica de la descendencia.
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