RESUMEN
The influence of maternal vitamin B12 malnutrition on testicular development of offspring was examined using soy protein-based B12-deficient diets with or without 0.5% DL-methionine supplementation. Dams were fed the B12-deficient diet throughout gestation and lactation, whereas dams in a control group were fed a control diet which contained cyanocobalamin in the B12-deficient diet without methionine. Offspring born to dams fed the B12-deficient diet without methionine showed poor testicular development, e.g. decreased numbers of seminiferous tubules containing healthy spermatocytes and a high ratio of apoptotic cells per all germ cells. The abnormality was rarely observed in the group fed the B12-deficient diet with methionine. It was likely that the testicular abnormality of offspring was caused by B12-deficiency post partum and was prevented by the methionine supplementation. These observations suggested that maternal B12 nutritional status during the pre-weaning period is quite important for spermatogenesis of male offspring and that the requirement of B12 for testicular development is to produce active B12-dependent methionine synthase.
Asunto(s)
5-Metiltetrahidrofolato-Homocisteína S-Metiltransferasa/metabolismo , Lactancia , Fenómenos Fisiologicos Nutricionales Maternos , Metionina/uso terapéutico , Testículo/crecimiento & desarrollo , Deficiencia de Vitamina B 12/complicaciones , Vitamina B 12/administración & dosificación , Animales , Animales Recién Nacidos , Dieta , Suplementos Dietéticos , Femenino , Masculino , Metionina/farmacología , Estado Nutricional , Embarazo , Efectos Tardíos de la Exposición Prenatal , Fenómenos Fisiologicos de la Nutrición Prenatal , Ratas , Ratas Wistar , Espermatogénesis , Enfermedades Testiculares/enzimología , Enfermedades Testiculares/etiología , Enfermedades Testiculares/prevención & control , Testículo/anomalías , Testículo/efectos de los fármacos , Deficiencia de Vitamina B 12/tratamiento farmacológico , Complejo Vitamínico B/administración & dosificaciónRESUMEN
BACKGROUND/AIMS: Vitamin B12 (B-12) is an essential cofactor for methionine synthase, and methionine is critical for the methylation of various biological molecules including DNA. Whether changes in B-12 levels can alter specific gene expression through DNA methylation and whether dietary methionine has any effect on general DNA methylation status still remains controversial. METHODS: We raised severely B-12-deficient rats as well severely-B-12 deficient rats but supplemented with 5% methionine. mRNA levels of methionine cycle-related enzymes were analyzed. RESULTS: Gene expression patterns changed under B-12-deficient conditions but were recovered by dietary methionine supplementation to B-12-deficient rats. However, cystathionine beta-synthase mRNA levels, which had decreased under B-12-deficient conditions, did not recover with supplementary dietary methionine. The CpG island of the cystathionine beta-synthase promoter was hypomethylated in B-12-deficient rats, and showed no recovery after methionine addition. CONCLUSIONS: Dietary B-12 can affect epigenetic machinery by regulating DNA methylation status and dietary methionine may have small effects on DNA methylation.