Methotrexate가 정자성숙에 미치는 영향에 관한 연구

Abstract

[한글]

The Study about the Effect of Methotrexate on the Sperm

Tae In Chung, M.D.

Department of Medical Science, The Graduate School, Yonsei University

(Directed by Prof. Gill Ryoung Kim, M.D.)

Since 1948, when the report of a dramatic effect of methotrexate, folic acid

antagonist, on acute leukemia of children was made by Farber et al., methotrexate

has been used widely and effectively for the treatment of various types of

malignancy, especially in acute leukemia, choriocarcinoma and psoriasis (Gubner,

1951; Wright, 1951; Chan, 1962; Li et al., 1960 -a, -b; Pace and Knoernschild,

1965).

The mechanism of the action of methotrexate is to its folic acid antagonistic

action on the purine, the pyrimidine and the thymidilic acid respectively, which

are essential in the synthesis of DNA through which cell reproduction is achieved

(Goldthwait and Bendich, 1952; Wright et al., 1958; Jaenicke and Wilmanns, 1963;

Werkheiser, 1963).

Methotrexate is a non-selective metabolic inhibitor affecting any type of cells

which are in the process of active proliferation, as well as cancer cells. Thus it

accompanies many side actions, such as abortion, congenital malformation, liver

cirrhosis, lung complication, renal complication, osteoporotic fracture and

especially oligospermia and teratospermia (Thiersch, 1952; Meltzer, 1956; Tan Scott

and Reinertson, 1959; Schoning, 1967).

The purpose of the present study is an attempt to relate DNA to the process of

maturation of sperm in the epididymis of the rats and the bulls, following

treatment with methotrexate in vivo and in vitro.

The DNA of sperm was determined by quantitative microspectrophotometric method

with Feulgen stain and qualitative liquid scintil1ation counter method with

thymidin-methyl-(3)**H.

The results were summarized as follows;

1. In the young rata treated with methotrexate, the Feulgen DNA of the sperm in

the epididymis was increased 18.05% and the number of the immature sperm cells was

increased.

2. In the adult rats treated with methotrexate, the Feulgen DNA of the sperm in

the epididymis was increased 20.30% and the number of the immature sperm cells was

increased,

3. In the young rats treated with methotrexate, the DNA of the sperm in the

epididymis was increased 19.l1% and the number of the immature sperm cells was

increased.

4. In the adult rats, the DNA of the sperm in the epididymis treated with

methotrexate in vitro was significantly decreased 19.34%.

5. In the bulls, the DNA of the sperm in the head portion of epididymis treated

with methotrexate in vitro was significantly decreased 16.90%.

6. In the bulls, the DNA of the sperm in the tail portion of the epididymis with

methotrexate in vitro did not decrease significantly 6.63%.

7. In the bulls, the DNA of the sperm in the head portion of epididymis was

increased more 27.74% than the sperm in the tail portion and the immature sperm

cells were found more in the head portion than in the tail portion.

It is speculated by above findings that methotrexate arrests not only in the

spermatogenesis, but also in the DNA synthesis of the sperm and in the process of

the maturation of the sperm in the epididymis.

[영문]

Since 1948, when the report of a dramatic effect of methotrexate, folic acid antagonist, on acute leukemia of children was made by Farber et al., methotrexate has been used widely and effectively for the treatment of various types of

malignancy, especially in acute leukemia, choriocarcinoma and psoriasis (Gubner, 1951; Wright, 1951; Chan, 1962; Li et al., 1960 -a, -b; Pace and Knoernschild, 1965).

The mechanism of the action of methotrexate is to its folic acid antagonistic action on the purine, the pyrimidine and the thymidilic acid respectively, which are essential in the synthesis of DNA through which cell reproduction is achieved

(Goldthwait and Bendich, 1952; Wright et al., 1958; Jaenicke and Wilmanns, 1963; Werkheiser, 1963).

Methotrexate is a non-selective metabolic inhibitor affecting any type of cells which are in the process of active proliferation, as well as cancer cells. Thus it accompanies many side actions, such as abortion, congenital malformation, liver

cirrhosis, lung complication, renal complication, osteoporotic fracture and especially oligospermia and teratospermia (Thiersch, 1952; Meltzer, 1956; Tan Scott and Reinertson, 1959; Schoning, 1967).

The purpose of the present study is an attempt to relate DNA to the process of maturation of sperm in the epididymis of the rats and the bulls, following treatment with methotrexate in vivo and in vitro.

The DNA of sperm was determined by quantitative microspectrophotometric method with Feulgen stain and qualitative liquid scintil1ation counter method with thymidin-methyl-(3)**H.

The results were summarized as follows;

1. In the young rata treated with methotrexate, the Feulgen DNA of the sperm in the epididymis was increased 18.05% and the number of the immature sperm cells was increased.

2. In the adult rats treated with methotrexate, the Feulgen DNA of the sperm in the epididymis was increased 20.30% and the number of the immature sperm cells was increased,

3. In the young rats treated with methotrexate, the DNA of the sperm in the epididymis was increased 19.l1% and the number of the immature sperm cells was increased.

4. In the adult rats, the DNA of the sperm in the epididymis treated with methotrexate in vitro was significantly decreased 19.34%.

5. In the bulls, the DNA of the sperm in the head portion of epididymis treated with methotrexate in vitro was significantly decreased 16.90%.

6. In the bulls, the DNA of the sperm in the tail portion of the epididymis with methotrexate in vitro did not decrease significantly 6.63%.

7. In the bulls, the DNA of the sperm in the head portion of epididymis was increased more 27.74% than the sperm in the tail portion and the immature sperm cells were found more in the head portion than in the tail portion.

It is speculated by above findings that methotrexate arrests not only in the spermatogenesis, but also in the DNA synthesis of the sperm and in the process of the maturation of the sperm in the epididymis.