118
S-2-4
Effects of Methyl Vitamin S. OSHIO,
Department 2-11-1,
of Kaga,
Urology, Itabashi-ku,
B12 on Sperm Quality
EYAZAKI,
Teikyo
University Tokyo 173
and
EUMEDA
School (Japan)
of
Medicine,
INTRODUCTION
Various drugs, such as amino acids, bromocriptine, clomiphene citrate, hormones, kallikreine and vitamins, have been used for pharmacological therapy of male infertility [1]. Sharp and Witts [2] reported that pernicous anemia patients with oligozoospermia treated with vitamin B12 showed an improvement in the oligozoospermia as well as the anemia. Since then vitamin B12 has become one of the useful drugs for male infertility, especially when the cause is oligozoospermia. Mecobalamin (a-(5,6-dimethyl benzimidazolyl) Co-methylcobamide : CH3-B12)is the most active of the vitamin B12 derivatives. It functions as a coenzyme in the synthesis of methionine from homocycteine and in the synthesis of phosphatidylethanolamine [3,4] and plays an important role in deoxyribonucleic acid synthesis [5]. Recently, Kimura et al. [6] showed that the sperm count and sperm motility of oligozoospermic patients increased after oral administration of CH3-B12. In sperm
the present production
ADRIAMYCIN
in
DAMAGES
study, we experimentally
THE
examined induced
SPERMATOGENESIS
the
IN
effect oligozoospermic
MICE
of
CH3-B12 mice.
on
[7]
Male ddY (10 weeks old) were administered adriamycin (ADM) subcutaneously at a dosage of 0.3 mg/kg three times a week for 5 weeks. At the same time, CH3-B12 was orally administered at dosages of 0.01,0.1, and 1mg 6 times a week for 10 weeks. The sperm count and sperm motility showed obvious decrease after ADM treatment, reaching 55% and 70 % of the saline control, respectively. Sperm motility recovered to the control level after CH3-B12 treatment (0.1and 1mg/kg). Motile sperm counts fell to 60 % of the control after ADM treatment, whereas they increased by CH3-1312 treatment (0.1 and 1mg/kg). In testicular morphology, suppression of spermatogenesis was observed after ADM injection (Fig.1). In contrast, the suppressed spermatogenesis almost recovered to the control level when 1mg/kg of CH3-B12 was orally administered. X-IRRADIATION TO THE TESTES IMPAIRS THE SPERMATOGENESIS IN MICE[8] Following anaesthetization, the testes of the mice (ICR strain, 8 weeks old) were acutely irradiated with 4 Gy of X-ray at a dose of 0.2 Gy/min, with shielding of the extra testicular region. From the next day after the irradiation, CH3-B12 was orally administered at dosages of 0.01,0.1, and 1mg/kg 6 times a week for 8 weeks. The control mice received physiological saline in the same manner. At 4 and 6 weeks after the irradiation, and epididymides were decreased, though those and accessory sex glands (seminal vesicle, prostate) were nearly equal to those of the At the same time, the diameter of the
the
weights of testes of the body weights coagulating gland and non-irradiated group. seminiferous tubules
S.OSHIO
decreased and sperm parameters (sperm deteriorated (Fig.2). When CH3-B12 the diameter of the seminiferous parameters improved as compared. with
et al
11 9
count, motility, morphology) (1mg/kg) was administered, tubules increased and sperm those of the control (Fig.2).
VITAMIN B12-DEFICIENCY INDUCES THE ARREST OF SPERMATOGENESIS IN MICE [9] Male ddY mice (10 weeks old) were fed with a vitamin B12deficient diet for 10 weeks. At the same time, CH3-B12 was orally administered at dosages of 0.01,0.1, and 1mg 6 times a week for 0 weeks. The control animals fed with a regular diet and 1 received saline orally. At 10 weeks, sperm parameters, testicular morphology and the vitamin B12 content of the serum and testis were examined. The deficiency of vitamin 812 for 10 weeks suppressed the growth rate of the testis. At that time, testicular morphology showed decrease in the diameter of the seminiferous tubules in the deficient-diet group. The sperm count and motile sperm count of the vitamin B12-deficient mice were also reduced (Fig.3). When CH3-B12 was administered during a feeding of a vitamin B12 deficient diet, the content of vitamin 812 in the serum and testis, and all of the above parameters recovered to the control level (Fig.3). On the other hand, when dimethylbenzimidazoie cobamide coenzyme (DBCC:1mg/kg) was administered, the content of vitamin 812 in the serum and testis increased to those in the CH33,2 group, but sperm parameters did not change (Fig.3). 1
DISCUSSION
It has pharmacological [2] first oligozoospermia oligozoospermia 6] reported
ABFig.i:
been
reported that various drugs have been used for therapy of male infertility [1]. Sharp and Witts reported that pernicious anemia patients with treated with vitamin B12 showed an improvement in as well as the anemia. Recently, Kimura et al., that the semen quality of infertile men was improved [
Cross section of mouse testis treated. with and without CH3-B12 after adriamycin injection. A: Control (ADM-saline), B: 1mg/kg CH3-1312 Adriamycin was administered subcutaneously for 5 weeks at the same time CH3-B12 (B) and equal volume of saline were administered orally for 10 weeks.
and (B)
Symposium (2)
120
Fig.2:
Effect on sperm Values
of
CH3-B12 motility. indicates
mean •} S.E. *:P
S-2-4
Effects of Methyl Vitamin S. OSHIO,
Department 2-11-1,
of Kaga,
Urology, Itabashi-ku,
B12 on Sperm Quality
EYAZAKI,
Teikyo
University Tokyo 173
and
EUMEDA
School (Japan)
of
Medicine,
INTRODUCTION
Various drugs, such as amino acids, bromocriptine, clomiphene citrate, hormones, kallikreine and vitamins, have been used for pharmacological therapy of male infertility [1]. Sharp and Witts [2] reported that pernicous anemia patients with oligozoospermia treated with vitamin B12 showed an improvement in the oligozoospermia as well as the anemia. Since then vitamin B12 has become one of the useful drugs for male infertility, especially when the cause is oligozoospermia. Mecobalamin (a-(5,6-dimethyl benzimidazolyl) Co-methylcobamide : CH3-B12)is the most active of the vitamin B12 derivatives. It functions as a coenzyme in the synthesis of methionine from homocycteine and in the synthesis of phosphatidylethanolamine [3,4] and plays an important role in deoxyribonucleic acid synthesis [5]. Recently, Kimura et al. [6] showed that the sperm count and sperm motility of oligozoospermic patients increased after oral administration of CH3-B12. In sperm
the present production
ADRIAMYCIN
in
DAMAGES
study, we experimentally
THE
examined induced
SPERMATOGENESIS
the
IN
effect oligozoospermic
MICE
of
CH3-B12 mice.
on
[7]
Male ddY (10 weeks old) were administered adriamycin (ADM) subcutaneously at a dosage of 0.3 mg/kg three times a week for 5 weeks. At the same time, CH3-B12 was orally administered at dosages of 0.01,0.1, and 1mg 6 times a week for 10 weeks. The sperm count and sperm motility showed obvious decrease after ADM treatment, reaching 55% and 70 % of the saline control, respectively. Sperm motility recovered to the control level after CH3-B12 treatment (0.1and 1mg/kg). Motile sperm counts fell to 60 % of the control after ADM treatment, whereas they increased by CH3-1312 treatment (0.1 and 1mg/kg). In testicular morphology, suppression of spermatogenesis was observed after ADM injection (Fig.1). In contrast, the suppressed spermatogenesis almost recovered to the control level when 1mg/kg of CH3-B12 was orally administered. X-IRRADIATION TO THE TESTES IMPAIRS THE SPERMATOGENESIS IN MICE[8] Following anaesthetization, the testes of the mice (ICR strain, 8 weeks old) were acutely irradiated with 4 Gy of X-ray at a dose of 0.2 Gy/min, with shielding of the extra testicular region. From the next day after the irradiation, CH3-B12 was orally administered at dosages of 0.01,0.1, and 1mg/kg 6 times a week for 8 weeks. The control mice received physiological saline in the same manner. At 4 and 6 weeks after the irradiation, and epididymides were decreased, though those and accessory sex glands (seminal vesicle, prostate) were nearly equal to those of the At the same time, the diameter of the
the
weights of testes of the body weights coagulating gland and non-irradiated group. seminiferous tubules
S.OSHIO
decreased and sperm parameters (sperm deteriorated (Fig.2). When CH3-B12 the diameter of the seminiferous parameters improved as compared. with
et al
11 9
count, motility, morphology) (1mg/kg) was administered, tubules increased and sperm those of the control (Fig.2).
VITAMIN B12-DEFICIENCY INDUCES THE ARREST OF SPERMATOGENESIS IN MICE [9] Male ddY mice (10 weeks old) were fed with a vitamin B12deficient diet for 10 weeks. At the same time, CH3-B12 was orally administered at dosages of 0.01,0.1, and 1mg 6 times a week for 0 weeks. The control animals fed with a regular diet and 1 received saline orally. At 10 weeks, sperm parameters, testicular morphology and the vitamin B12 content of the serum and testis were examined. The deficiency of vitamin 812 for 10 weeks suppressed the growth rate of the testis. At that time, testicular morphology showed decrease in the diameter of the seminiferous tubules in the deficient-diet group. The sperm count and motile sperm count of the vitamin B12-deficient mice were also reduced (Fig.3). When CH3-B12 was administered during a feeding of a vitamin B12 deficient diet, the content of vitamin 812 in the serum and testis, and all of the above parameters recovered to the control level (Fig.3). On the other hand, when dimethylbenzimidazoie cobamide coenzyme (DBCC:1mg/kg) was administered, the content of vitamin 812 in the serum and testis increased to those in the CH33,2 group, but sperm parameters did not change (Fig.3). 1
DISCUSSION
It has pharmacological [2] first oligozoospermia oligozoospermia 6] reported
ABFig.i:
been
reported that various drugs have been used for therapy of male infertility [1]. Sharp and Witts reported that pernicious anemia patients with treated with vitamin B12 showed an improvement in as well as the anemia. Recently, Kimura et al., that the semen quality of infertile men was improved [
Cross section of mouse testis treated. with and without CH3-B12 after adriamycin injection. A: Control (ADM-saline), B: 1mg/kg CH3-1312 Adriamycin was administered subcutaneously for 5 weeks at the same time CH3-B12 (B) and equal volume of saline were administered orally for 10 weeks.
and (B)
Symposium (2)
120
Fig.2:
Effect on sperm Values
of
CH3-B12 motility. indicates
mean •} S.E. *:P
