Effects of Vitamin B12-Deficiency on Testes Tissue in Rats.

Kawata, Toshitsugu; Takada, Tomomi; Morimoto, Fusako; Fujimoto, Naoko; Tanaka, Nobuo; Yamada, Keiko; Wada, Masahiro; Tadokoro, Tadahiro; Maekawa, Akio

doi:10.3177/jnsv.38.305

Cited by 22 publications

(20 citation statements)

References 20 publications

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“…The testicular histologic changes in N2O-exposed rats are similar to those seen in dietary B12-deficient rats, as follows: B12-deficient rats had a reduced wet weight in their testes (10,11) and the dry weight of testes from the N2O-exposed rats was also lower after 32 d of N2O exposure (21). Both rats' testes show abnormal spermatogenesis, such as aplasia of sperm and spermatoids.…”

Section: Discussionmentioning

confidence: 53%

“…We found that B 12 -deficient rats and mice fed a B 12 -deficient diet in which soybean protein was used as a protein source showed severe damage of testicular tissue accompanying weight loss (10)(11)(12). In fact, there are independent reports about male infertility accompanying B 12 -deficiency, and improvement of sperm motility upon B 12 administration (13)(14)(15)(16)(17).…”

Section: Testicular Injury To Rats Fed On Soybean Protein-based Vitammentioning

confidence: 99%

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Testicular Injury to Rats Fed on Soybean Protein-Based Vitamin B12-Deficient Diet Can Be Reduced by Methionine Supplementation

Yamada

Kawata

Wada

et al. 2007

J Nutr Sci Vitaminol

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SummaryWe have previously reported that rats fed on a vitamin B 12 (B 12 )-deficient diet containing 180 g soybean protein per kg diet showed marked histologic damage in their testes. In this paper, we report the effect of B 12 -deficiency on B 12 -dependent methionine synthase in the rats' testes and the effect of methionine supplementation of the diet on testicular damage. Rats were fed the soybean protein-based B 12 -deficient diet for 120 d. We confirmed that those rats were in serious B 12 -deficiency by measuring urinary methylmalonic acid excretion and B 12 content in tissues. Methionine synthase activity in the testis of the B 12 -deficient rats was less than 2% of that in B 12 -supplemented (control) rats. To complement disrupted methionine biosynthesis, methionine was supplied in the diet. A supplement of 5 g D,L-methionine per kg diet to the B 12 -deficient diet did not affect urinary methylmalonic acid excretion of B 12 -deficient rats. The testicular histology of rats fed the methioninesupplemented B 12 -deficient diet was almost indistinguishable from that of control rats. Thus, we conclude that the lowered testicular methionine synthase activity is the primary cause of the histologic damage due to B 12 -deficiency and that methionine supplementation to the diet can reduce the damage. These findings would indicate the importance of the methionine synthase activity, especially for testicular function. Key Words vitamin B 12 -deficiency, rat, testis, methionine synthase In mammals, vitamin B 12 (B 12 ) acts as a cofactor for two enzymes, methylmalonyl-CoA mutase and methionine synthase. Adenosylcobalamin is required for methylmalonyl-CoA mutase, which catalyzes a reaction that interconverts succinyl-CoA and methylmalonylCoA. Dysfunction of methylmalonyl-CoA mutase causes methylmalonic aciduria. Methylcobalamin (MeB 12 ) binding to methionine synthase serves as an intermediary in methyl transfer from methyltetrahydrofolate to homocysteine, donating the methyl group to homocysteine to form methionine, and then accepting a methyl group from methyltetrahydrofolate to form tetrahydrofolate. Methionine synthase is important both to resynthesize methionine and to metabolize methyltetrahydrofolate. Tetrahydrofolate accepts C1-groups from serine or formate. Then, the C1-group can be donated to either homocysteine to form methionine or deoxyuridine monophosphate to form deoxythymidine monophosphate. The C1-group also is precursor in de novo purine biosynthesis. Methionine is one of the amino acids that are building blocks for protein. In addition, methionine is activated to S -adenosylmethionine (AdoMet), which is well known as a major methyldonor for numerous substrates and an allosteric regulator for methylenetetrahydrofolate reductase (MTHFR) and cystathionine-␤ -synthase. While causal of symptoms related with dysfunction of methionine synthase, such as megaloblastic anemia and neuropathy, might be explained by the "Methyl trap" hypothesis ( 1-4 ), the biochemical mechanism has not yet been fully understoo...

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Section: Discussionmentioning

confidence: 53%

Section: Testicular Injury To Rats Fed On Soybean Protein-based Vitammentioning

confidence: 99%

Testicular Injury to Rats Fed on Soybean Protein-Based Vitamin B12-Deficient Diet Can Be Reduced by Methionine Supplementation

Yamada

Kawata

Wada

et al. 2007

J Nutr Sci Vitaminol

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“…However, no changes in both vitamin B 12 and homocysteine levels were detected in the cimetidine-treated rats, indicating that the treatment with cimetidine was not able to induce vitamin B 12 deficiency. Dietary deficiency in animals, including rats [Williams et al, 1969;Kawata et al, 1997], is difficult to be induced and tends to give variable results, since the biological half-life of B 12 is long and, subsequently, B 12 deficiency takes a lot of time to be manifested [Kawata et al, 1992]. In some experimental studies, B 12 -deficient newborn rats have been obtained from pregnant female rats fed on a B 12 -deficient diet during pregnancy and lactation [Kawata et al, 1992[Kawata et al, , 1997[Kawata et al, , 2004.…”

Section: Effect Of Vitamin B 12 In the Cimetidine-treated Ratsmentioning

confidence: 99%

“…In the testis, vitamin B 12 has demonstrated to play a role in the maintenance of testicular functions [Hata et al, 2002;Webster et al, 2005;Yamada et al, 2007]. In vitamin B 12 -deficient rodents, testicular pathological disorders have been demonstrated, such as significant reduction of testis weight, atrophy of the seminiferous tubules and aplasia of spermatids and sperm [Kawata et al, 1992[Kawata et al, , 1997[Kawata et al, , 2004. Regarding the reproductive performance in humans, studies revealed that spermatogenesis would be improved when a large amount of vitamin B 12 is given to patients with oligospermia [Sharp and Witts, 1962].…”

Section: Introductionmentioning

confidence: 99%

Vitamin B<sub>12</sub> Supplement Exerts a Beneficial Effect on the Seminiferous Epithelium of Cimetidine-Treated Rats

Beltrame

Caneguim

Miraglia

et al. 2010

Cells Tissues Organs

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Treatment of gastric ulcer with cimetidine reduces acid secretion and interferes in the vitamin B₁₂ absorption. Regarding the harmful effect of cimetidine on the seminiferous tubules, the aim of the present study was to verify if prolonged treatment with cimetidine causes vitamin B₁₂ deficiency and whether the testicular damages are attenuated by vitamin B₁₂ supplementation. Adult male rats received, for 50 days, cimetidine (CMTG), cimetidine and vitamin B₁₂ (CMT/B₁₂G), vitamin B₁₂ (B₁₂G) and saline solution (CG). Vitamin B₁₂ and homocysteine plasma levels were evaluated and the testes were embedded in glycol methacrylate for the morphometric analyses of total, epithelial and luminal areas of the seminiferous tubules, number of Sertoli cells and frequencies of tubules according to stages and containing Sertoli and germ cells in the lumen. Terminal deoxynucleotidyl-transferase mediated dUTP nick end labeling (TUNEL) method and proliferating cell nuclear antigen (PCNA) immunohistochemistry were carried out. CMTG showed TUNEL-positive Sertoli cells and significant reductions in the epithelial and total tubular areas, number of Sertoli cells and frequency of tubules VII-VIII. In the CMT/B₁₂G, the number of Sertoli cells and the epithelial and total tubular areas were similar to CG. The number of Sertoli cells (in B₁₂G) and the frequency of tubules at stages VII-VIII (in B₁₂G and CMT/B₁₂G) increased significantly; PCNA-positive Sertoli cells were found in these groups. Although cimetidine was not able to induce vitamin B₁₂ deficiency, this drug causes tubular atrophy due to Sertoli cell damage and loss of germ cells. However, vitamin B₁₂ supplement is able to stimulate spermatogenesis and restore the number of Sertoli cells, softening the harmful effect of cimetidine on spermatogenesis.

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“…It has also been reported that VB12 defi ciency causes testis histological alteration (28), but there is no report about the relation between testosterone and VB12. Furthermore, there is no report about the interaction between biotin and VB12 on testosterone secretion.…”

Section: Discussionmentioning

confidence: 99%

The Interactive Effect of Dietary Water-Soluble Vitamin Levels on the Depression of Gonadal Development in Growing Male Rats Kept under Disturbed Daily Rhythm

Hanai

ESASHI

2012

J Nutr Sci Vitaminol

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230The number of people living under disturbed daily rhythm has been increasing due to the globalization of business and social activities as well as the diversifi cation of the forms of labor. Such irregularities in daily rhythm adversely affect bio-regulatory mechanisms, resulting in an abnormal diurnal rhythm that can impede biological activities structurally and functionally. However, there is currently no source of collected basic data on the nutritional aspects of maintaining or promoting health under the condition of disturbed daily rhythm. The perspective behind this research is as follows: as basic data on the relationship between nutritional status and gonadal development in rats with disturbed daily rhythm accumulate, these data can be used for human research, and fi nally, dietary reference intakes can be compiled for persons living under disturbed daily rhythm.Lighting is one of the key external factors for the formation of daily rhythm. Rats kept under constant darkness develop disturbances in their feeding and motoractivity rhythms, and suffer from altered rhythms of hormone secretion and enzyme activity (1, 2). Esashi et al. (3,4) have reported that rats kept under constant darkness showed depressed gonadal development and a decreased delivery rate. The depression of gonadal development in these rats was accelerated by a low-protein diet (4). These fi ndings indicate that the gonads have high sensitivity to constant darkness and nutrients.In previous papers, we have reported the effects on rat gonadal development of protein, methionine, vitamins, minerals and oil (5), minerals (6), amino acids, an AIN-76 diet and an AIN-93G diet (7), the interaction between protein and vitamins (8), water-and fat-soluble vitamins (9) and each of the fat-soluble vitamins (10). We have demonstrated that a high level (three times the normal (AIN-93G)) of water-soluble vitamin and a low level (1/3.3 of normal) of fat-soluble vitamin diet mitigated the depression of gonadal development in rats kept under constant darkness (9). Therefore, as a next step, we attempted to clarify the effects on gonadal development of nine kinds of water-soluble vitamins under a diet with a low level of fat-soluble vitamins. In this experiment, the content of each water-soluble vitamin was normal or six times the normal content. This study was divided into two experiments, because a single experiment to test all nine water-soluble vitamins couldn't be done. In the fi rst experiment (Ex. 1) we examined seven water-soluble vitamins, and in the second experiment (Ex. 2) we examined two water-soluble vitamins. Experiment 1 was carried out using an orthogonal array (11, 12), which is the experimental design we applied in previous studies (5-7, 10), and Ex. Summary The purpose of this study was to clarify the effects of nutrients on the gonadal development of male rats kept under constant darkness as a model of disturbed daily rhythm. In the present study we examined the effects of nine water-soluble vitamins. We selected 7 water-soluble vitam...

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Effects of Vitamin B12-Deficiency on Testes Tissue in Rats.

Cited by 22 publications

References 20 publications

Testicular Injury to Rats Fed on Soybean Protein-Based Vitamin B12-Deficient Diet Can Be Reduced by Methionine Supplementation

Testicular Injury to Rats Fed on Soybean Protein-Based Vitamin B12-Deficient Diet Can Be Reduced by Methionine Supplementation

Vitamin B<sub>12</sub> Supplement Exerts a Beneficial Effect on the Seminiferous Epithelium of Cimetidine-Treated Rats

The Interactive Effect of Dietary Water-Soluble Vitamin Levels on the Depression of Gonadal Development in Growing Male Rats Kept under Disturbed Daily Rhythm

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