Abstract
Vitamin C (VC) is well known as an antioxidant in humans, primates and guinea pigs. Studies have suggested gender differences in VC requirements in humans, and gender differences in oxidant injury vulnerability in early life may represent a biological mechanism contributing to gender disparity in later life. Using spontaneous bone fracture (sfx) mice, which lack the gene for L-Gulonolactone oxidase (Gulo), we studied the potential sex difference in expression profiles of oxidative genes at the whole-genome level. Then, we analyzed data of gene expressions in a mouse population of recombinant inbred (RI) strains originally derived by crossing C57BL/6J (B6) and DBA/2J (D2) mice. Our data indicated that there were sex differences in the regulation of pre- and pro-oxidative genes in sfx mice. The associations of expression levels among Gulo, its partner genes and oxidative genes in the BXD (B6 × D2) RI strains showed a sex difference. Transcriptome mapping suggests that Gulo was regulated differently between female and male mice in BXD RI strains. Our study indicates the importance of investigating sex differences in Gulo and its oxidative function by using available mouse models.
Highlights
In humans, a gender difference in vitamin C (VC) requirement has been suggested by several studies
We discovered that the sfx model lacks the gene for L-Gulonolactone oxidase (Gulo), a key enzyme in the ascorbic acid (AA) synthesis pathway [12]
Our results are from two sets of experiments
Summary
A gender difference in vitamin C (VC) requirement has been suggested by several studies. 69-year-old Japanese to ascertain the influences of a 677C-T methylene-tetrahydrofolate reductase (MTHFR) genotype, nutritional intake and lifestyle-related factors on plasma homocysteine (Hcys) and serum folate concentrations They found that log folate intake per 1,000 kcal in males was a significant and positive predictor of log serum folate concentration (p < 0.01), while in females, the log VC intake per standard body weight was a significant and positive variable (p < 0.001) predicting the log serum folate concentration. Beitz et al [4] found that, when information about VC and fruit and vegetable intake was considered simultaneously, a high fruit and vegetable intake was more strongly associated with lower systolic blood pressure levels, as compared with high VC intake among women They did not find significant associations between blood pressure and vitamin C and fruit and vegetable intake among men. We report the potential difference in expression profiles of oxidative genes at the whole-genome level in sfx mice and in BXD RI mouse strains. Because the gender difference in VC requirement has been known and because of the known oxidative function of VC, we decided to investigate whether there is a sex difference in the effect of expression levels of oxidative-relevant genes because of a lack of VC and whether the effect on oxidative genes of VC is related hormones stimulation
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