Maternal folic acid depletion during early pregnancy increases sensitivity to squamous tumor formation in the offspring in mice.
J Dev Orig Health Dis
; 10(6): 683-691, 2019 12.
Article
en En
| MEDLINE
| ID: mdl-31131784
ABSTRACT
Gestational nutrition is widely recognized to affect an offspring's future risk of lifestyle-related diseases, suggesting the involvement of epigenetic mechanisms. As folic acid (FA) is a nutrient essential for modulating DNA methylation, we sought to determine how maternal FA intake during early pregnancy might influence tumor sensitivity in an offspring. Dams were maintained on a FA-depleted (FA(-)) or normal (2 mg FA/kg; FA(+)) diet from 2 to 3 days before mating to 7 days post-conception, and their offspring were challenged with chemical tumorigenesis using 7,12-dimethylbenz[a)anthracene and phorbol 12-myristate 13-acetate for skin and 4-nitroquinoline N-oxide for tongue. In both squamous tissues, tumorigenesis was more progressive in the offspring from FA(-) than FA(+) dams. Notably, in the skin of FA(-) offspring, the expression and activity of cylindromatosis (Cyld) were decreased due to the altered DNA methylation status in its promoter region, which contributed to increased tumorigenesis coupled with inflammation in the FA(-) offspring. Thus, we conclude that maternal FA insufficiency during early pregnancy is able to promote neoplasm progression in the offspring through modulating DNA methylation, such as Cyld. Moreover, we propose, for the first time, "innate" utero nutrition as the third cause of tumorigenesis besides the known causes-hereditary predisposition and acquired environmental factors.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Efectos Tardíos de la Exposición Prenatal
/
Neoplasias Cutáneas
/
Neoplasias de la Lengua
/
Carcinoma de Células Escamosas
/
Fenómenos Fisiologicos Nutricionales Maternos
/
Ácido Fólico
/
Deficiencia de Ácido Fólico
Tipo de estudio:
Diagnostic_studies
/
Etiology_studies
Límite:
Animals
/
Pregnancy
Idioma:
En
Revista:
J Dev Orig Health Dis
Año:
2019
Tipo del documento:
Article
País de afiliación:
Japón