Abnormal gene methylation during embryonic development after preimplantation genetic testing increases risk of liver-derived insulin resistance.
Ann N Y Acad Sci
; 1425(1): 70-81, 2018 08.
Article
en En
| MEDLINE
| ID: mdl-29873092
The operations involved in preimplantation genetic testing (PGT) occur during the key stages of gametogenesis and early embryonic development, and the health of progeny following PGT (PGT-born) is worthy of attention. In order to fully assess the potential risk of abnormal glucose metabolism in adult PGT-born offspring and to evaluate possible mechanisms, we compared a mouse model of PGT (in vitro cultured embryos with biopsy, hereafter "PTG-born mice"), an in vitro embryo manipulation mouse model (in vitro cultured embryos without biopsy), and normal mice. PGT-born mice displayed increased fasting glucose, and decreased glycogen synthesis and glucose oxidative utilization in the liver. Moreover, PGT-born mice also displayed reduced expression of insulin receptor, AKT, and insulin-stimulated Akt phosphorylation (pAkt) in the liver. These results suggest a potential risk of insulin resistance in adult PGT-born mice. By analyzing the DNA methylation profiles of 7.5 days postconception (dpc) embryos, we identified differentially methylated genes associated with liver development between PGT-born and control groups; some of these genes are associated with glucose homeostasis and insulin response. These results suggest that abnormal methylation in embryos that develop after PGT may be a potential mechanism occurring during embryonic development that can influence the risk of liver-derived insulin resistance in adulthood.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Resistencia a la Insulina
/
Pruebas Genéticas
/
Metilación de ADN
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Diagnóstico Preimplantación
/
Desarrollo Embrionario
/
Hígado
Tipo de estudio:
Diagnostic_studies
/
Etiology_studies
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Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
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Female
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Humans
/
Pregnancy
Idioma:
En
Revista:
Ann N Y Acad Sci
Año:
2018
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos