Influences of maternal B12 and methionine intake during gestation and lactation on testicular development of offspring in rats.

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.

Change of epigenetic control of cystathionine beta-synthase gene expression through dietary vitamin B12 is not recovered by methionine supplementation.

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.