DM과 DEHP 투여가 생쥐의 정액성상과 장기무게에 미치는 영향

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DM 과

DEHP

^Ã~

^QHA -,

^{-I ι샤깐 L} --.

김성곧

·

·

·

^‘’

·

강원대학교 동물자원과학대학 뚫물자원학부

미치는 영향

Effect of DM and DEHP administration on semen characteristic and organ weight in mice

Kim. S. K. , D. H. Park , C. K. Park , C. I. K Íl u , H. T. Cheong and B. K. Yang*

Division of AnimaJ Resource Science , CoJJege of AnimaJ Resource Science

ABSTRACT

Endocrine disruptors are exgenous chemical that interfere to several aspects of natural hormone properties. D EHP( di-2-ethyhexylphthalate) is classified suspect that have a similar nature to endocrine disruptors. D M (dextromethorphan) is widely used the cough drug , which may cause the noxious effect to reproductive function.

This study were performed to investigate the effect of D EHP and D M administration on semen characteristic and body or organ weight in mice.

In D M and D EHP administration for 15 days or 29 days , total sperm concentration and viability were lower in DM(26.7 X 1Q 6/ m1 and 19.0x 1Q 6/ m1 , 1 1. 7% and 12.3%) and DEHP(2 1. 7x 1Q 6/ m1 and 19 .1 X 1Q 6/ m1 , 15.0% and 16 .4%) than in control group(52.5X 1Q 6/ m1 and 4 1. 7X 1Q 6/ m1 , 39.7% and 44 .4%), respectively. The proportion of sperm abnormality were significantly increased in D M and D EHP administration groups for 15 days or 29 days than in control group(P(0.05)'

The administration of D M or D EHP in mice didn't affect the body and reproductive organ weight such as testis , epididymis , vasicular gland and coagulatin gland. The organ weigh t( spleen , liver and kidney) were slightly affect in D M and D EHP administration groups for 15 days or 29 days.

This studies indicate the short or long term D M and D EHP administration were noxious effects on the sperm characteristics , organ weight such as liver , spleen or kidney , but didn ’ t affect body and reproductive organs weight in mice.

Key words DEHP , dextro methorphan , endocrine disruptor , Semen characteristic

* Correspondence Tel 033-250-8623 , E-mail bkyang@kangwon.ac.kr

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동물자원연구 (2000)

1 .

내분비계 장애물질이란 체내의 항상성을 유지하고， 성장발욕과 생식과정을 조절하는 천연호르몬의 생산， 분비， 이동， 대사， 결합작 용 및 배설 등을 방해하는 체외물질이라고 미극 환경보호극은 정의하고 있으며， 현재 우리나라에서는 세계야생보호기금이 선정한 67종을 내분비계 장애물질로 지정하고 있으 며 이중 4종을 관찰물질로 지정하고 있다.

내분비 계 관찰물질 중

di-2-ethyhexylphthalate

(DEHP) 는 저렴한 가격과 가소성 때문에 세계적 으로 폭넓게 사용하고 있으며 혈액과 혈액생산물 을 저장하는

bag

1987).

Srivastava ^, 1992) ^,

1986) ^,

1993) , Sertoli

1997) ,

Hiraga ^, 1979) ^, testos

Hiraga ^, 1980b)

Zn

Williams ^, 1993 D ybing

IPCS ^, 1992).

D extromethorphan (D M)

,

1977).

(Frank

Evelyn

1996) .

이것은 신경약학 측면에서 영향을 미치지 않 지만 뇌에 멀접한 관계가 있어 뇌혈관과 대 뇌 벚 호르몬 대사에 영향을 미치는 것으로

알려져 있다 (Frank 등， 1989

D ematteis

1997) .

dextrorphan (D 0)

(Lennart

1988).

본 연구는 내분비계 장애물질 중 관찰물질 로 분류되어 있는 DEHP 와 기침약에 이용되 는 성분중 하나인 DM의 투여가 생쥐의 정 액성상과 번식기관 벚 장기무게에 미치는 영 향을 검토하고자 실시하였다.

ll.

1.

실험동물은 강원대학교 동물자원과학대학 실험동물 사욱실에서 자체 교배시켜 생산된

11

2. DM

DEHP

DM은

dextromethorphan

DEHP

(Sigma) 의 제조는

DEHP

corn

oil과 섞어서 제조하였다. 투여방법은 대조구 는

corn

2

일 간격으로 15 일과 29 일동안 복강주사로 투 여하였으며， 투여후

1. 3 ^,

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3

( 1 )

정액의 채취는 웅성생쥐를 경추탈골 시킨 후， 우측 정소상체 미부를 적출하여 5% 의 자우혈청

(Fetal bovine serum , FBS Gibco)

이 첨가된 saline 에 첨가하여 안과가위로 셰 절 한 후

3Tc

warming

eppendorf

(2)

1)

2)

Haemacytometer를

Makler Counting Chamber(Sefi-Medical Instrument ,

5% FCS( Gibco ,

saline 1. 8

10

배(1 :9) 로 희석한 다음， 현미경하 (200배)에서 사별정자，진자운동정자， 회전운동정자，머리 가 절단된 정자등을 계산하고， -20^oc 에서

15

분간 동결시킨 후 융해한 다음 총정자수를 계산하여 전진운동 비율을 계산하였다.

3)

정소상체 미부에서 채취한 정액 200 t11 에

saline 4

saline

slide

50 t1 1

3Tc warming

조시 켰다. 건조된

slide

0.5ml

Rose

-Bengal

시켜 증류수에 5~6 회 담그고 꺼내는 방식으 로 염색액을 제거한 다음， 완전건조 시킨후 위상차 현미경 (400배)에서 기형정자를 관찰 하였다.

4.

개시체중과 종료시 체중을 측정한 후 웅성 생쥐를 경추탈골 시킨 후 안과 가위로 간，

비 장， 신 장을 적 출하여

filter

정냥션 벚 응고션을 적출한 후 정소와 정소 상체 를 짤라내 어

filter

5.

본 실험에서 얻어진 결과를

Doncan ’ s Multiple

Range

였다.

ID. 결 과

1.

DEHP

ICR

Table

2

Fig. 1

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동물자원연구 (200이

Table 1. Effect of DM and DEHP administration for 2weeks on semen characteristic in mice

Treatment Sperm con. ¹ Viab ⁱ¹ⁱ ty Abnormality

( x 106/ 떼 ) ( %) ( %)

Control 52.5 :t 11.8 ^a 39.7 :t l 1. 3 ^a 14.3 :t 4.8 ^c

DM ^Z 26.7 :t 1 3. 3 ^b l 1. 7 :t 8 .5 ^b 20.6 :t 7.2 ^b

DEHPj 2 ^1. 7 :t 10.4 ^c 15.0 :t 9.5 ^b 24.0 :t 6 .1 a

a.b.c D ifferent superscripts within columns are significantly differ , P<0.05.

1. Sperm concentration 2. D extromethorphan 3. di-2-ethyhexylphthalate

표 1 에 나타난 바와 같이 DM과

DEHP

⁶ / ml , DM

X 10 ⁶ / ml ,

2 1. 7 X 10 ⁶ /

(P<0.05) ,

39 .7%, DM

1 1. 7% , DEHP

14.3% , DM

20.6% , DEHP

투여구는 24.0% 로 DM과

DEHP

표 2에서 나타난 바와 같이 총정자수는 대 조구가

4 1. 7x10 ⁶ /ml , DM

19.0x 10 ⁶ / ml , D EHP

19.1 X 10 ⁶ /

조구는

44 .4%, DM

12.3% , DEHP

투여구는 16.4%로서 대조구가 처리구에 비 해 높은 성적을 나타냈다 (P<0.05L 반면 기형 율은

DM

25.2% , DEHP

Table 2. Effect of DM and DEHP administration for a month on semen characteristic in mice

Treatment Sperm con. ¹ Viability Abnormality

( x 106/ 떼 ) ( %) ( %)

Control 4 1. 7 :t 12.0 ^a 44 .4:t l 1. 9 ^a 16.7 :t 3 .4 ^b

DM ² 19.0 :t 7.8 ^b 12.3 :t 6 ^{.1 b} 25.2 :t 7.0 ^a

DEHpJ 19 .1 :t 8.0 ^b 16 .4:t 7.0 ^b 26.0 :t 6 .1 a

a.b D ifferent superscripts within columns are significantly differ ^‘ P<0.05.

1. Sperm concentration 2. D extromethorphan 3. di-2-ethyhexy lphthala te

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명￡

(

×

A

” m gm t 」

m

Q ”

•

Days after last injection

Fig. 1. Effect of DM and DEHP administration on sperm concentration in mice. Mice were injected DM(30mg/kg BW) or DEHP( lO mg/kg BW) for 15 days in two days intervals.

a.b.c Different superscripts within experimental day are significantly differ , P<O.05.

Fig.

DEHP

1, 3 ^,

47.9 , 80.9 x

10 ⁶ /

DM

24.0 , 2 1. 4 x 10 ⁶ /

ml)와

DEHP

16.5 ^, 24.5 x 10 ^{6 /}

m l)

( P<0.05).

ηζ

영

) ~:

---D

m

->

Days after last injection

Fig. 2. Effect of DM and DEHP administration on sperm viability in mice. Mice were injected DM(30mg/kg BW) or DEHP( lO mg/kg BW) for 15 days in two days intervals.

a.b Different superscripts within experimental day are significantly differ , P<O.05.

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동물자원 연구 (2000)

Fig.

DEHP

1, 3 ^,

39.6 ,

DM

9.5 , 23 .4 %

DEHP

13.3 ,

Fig.

DEHP

1, 3 ,

DM

18.9 ,

DEHP

23. 1, 25.8

00.8 , 15.1. 17 .1%)

@@)

〉프떠

IP〈

Days after last injection

Fig. 3. Effect of DM and DEHP administration on sperm abnomality in mice. Mice were injected DM(30mg/kg BW) or DEHP( lO mg/kg BW) for 15 days in two days intervals. 8.b.c Different superscripts within experimental day are significantly differ , P<O.05.

c。

。

잉 25

- ^m

20

。j

a

'"

-

。

z

Days after last injection

Fig. 4. Effect of DM and DEHP administration on sperm concentration in mice. Mice were injected DM(30mg/kg BW) or DEHP( lO mg/kg BW) for 29 days in two days intervals. 8.b.c Different superscripts within experimental day are significantly differ , P<O.05.

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Fig.

DEHP

1, 3 ,

43.3 , 37.8 x 10 ^{6 / m I)}

DM

(5.8 ^, 22 ^.4, 19.0 x 10 ^{6 /}

ml

DEHP

16 .4, 17.2 x 10 ⁶ /

Ll

> 20

Fig.

DEHP

1, 3 ^,

44.7 ,

DM

9 .4,

DEHP

15.6 , 17.0 ^,

(P<0.05L

Days after last injection

Fig. 5. Effect of DM and DEHP administration on sperm viability in mice. Mice were injected DM(30mg/kg BW) or DEHP( lO mg/kg BW) for 29 days in two days intervals. a , b Different

δ‘

)

>-

‘ m

superscripts within experimental day are significantly differ , P<O.05.

E 15

。 I j

<

10

Days after last injection

Fig. 6. Effect of DM and DEHP administration on sperm abnomality in mice. Mice were injected DM(30mg/kg BW) or DEHP( lO mg/kg BW) for 29 days in two days intervals. a , b Different superscripts within experimental day are significantly differ , P<O.05.

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동물자원 연구 (2000)

Fig.

DEHP

액성상 중 기형율에 미치는 영향을 29 일 동 안 주사후

1, 3 ,

DM(21.0 , 29. 1,

DEHP

(23 .1, 28 .4, 26.6 %

16.6 ,

2.

DEHP

DM과

DEHP

번식기관 및 장기무게에 미치는 영향을 표

3

과 4에 요약하였다.

개시체중과 종료시 체중을 보면 전 처리구에 서 유의성이 인정되지 않았다(P)O.05). 번식기관 무게에 있어서 정소， 정소상체， 정낭선 벚 응고 션의 무게도 전 처리구간에 유의성이 인정되지 않았다(P)O.05). 그러나 장기무게에서 간과 신장 의 무게는 대조구， DM투여구 벚

DEHP

모두 유의적인 차이는 보이고 있지 않지만， 비 장의 무게에 있어서 대조구는

O.115g , DM

0 .1 02g , DEHP

DEHP

3).

개시체중과 종료시 체중에 있어서 대조구，

DM

DEHP

없었다 (P)O.05). 또 번식기관 무게에서도 정소，

정소상체， 정냥선 빛 응고션의 무게에 있어서 도 유의적인 차이는 인정되지 않았다 (P)O.05).

그러나 장기무게 중 신장의 무게는 전처리구 간에 유의적 인 차이가 인정되지 않았지만

(P)O.05) ,

1.994g ,

DM

2.010g , D EHP

2.331g

으로서

DEHP

로 높은 성적을 나타냈고 (P(O.05) ， 비장의 무 게에 있어서도 대조구는

0 .1 18g , DM

0 .1 34g , D EHP

DEHP

높은 성적을 보이고 있다 (P(O.05)

(Table 4).

Table 3. Effect of DM and DEHP administration for 2 weeks on body weight and organ weight Day

Trea t. ^after last injection

Co n.

Mean

DM 5 Mean

DEHP 5 Mean

Body weight(g) Organ weight(g)

Vasicular Coagulatin

initial final Testis Epididymis ~~~O-.~V... Liver Kidney Spleen gland gland

34.7 :t 5 .4 35 .1:t 4.8 0.077 :t 0.043 0 .1 31 :t 0 .1 55 0.085 :t 0.027 0.011 :t 0.005 1. 832 :t 0.270 0 .3 70 :t 0.023 0 .1 26 :t 0.019 34 .4:t 3.2 38 .1:t 0 .4 0 .1 22 :t 0.005 0.041 :t 0.002 0.083 :t 0.022 0.006 :t 0.002 2.379 :t 0 .4 46 0 .3 49 :t 0.046 0 .1 17 :t 0.014 33.8 :t1. 7 34.8 :t 3 .1 0.117 :t 0.006 0.043 :t 0.003 0.072 :t 0.020 0.055 :t 0.001 1.826 :t 0퍼7 0.333 :t 0.047 0 .1 03 :t 0.009 34.3 :t 3.2 36.0 :t 3 .3 0 .1 05 :t 0.006 0.072 :t 0.094 0.080 :t 0.022 0.007 :t 0.004 2.012 :t 0 .4 11 0 .3 51 :t 0.041 0 .1 15 :t 0.016 ^b 34.5 :t 5 .7 34.7 :t 4 .1 0 .1 15 :t 0.020 0.037 :t 0.006 0.091 :t 0.022 0.009 :t 0.004 1. 859 :t 0.215 0 .3 54 :t 0.050 0.095 :t 0.019 34.5 :t 2.9 36.8 :t 3.8 0.118 :t 0.022 0.039 :t 0.004 0.057 :t 0.011 0.012 :t 0.001 2.277 :t 0.274 0 .4 06 :t 0.061 0 .1 05 :t 0.039 35.6 :t 0 .1 36.5 :t 0.0 0 .1 21 :t 0.008 0.033 :t 0.013 0.093 :t 0.019 0.005 :t 0.002 1. 839 :t 0.267 0 .3 15 :t 0.055 0 .1 09 :t 0.012 34.8 :t 3.5 35.9 :t 3.2 0 .1 18 :t 0.017 0.037 :t 0.007 0.079 :t 0.025 0.009 :t 0.004 2.011 :t 0.306 0.364 :t 0.064 0 .1 02 :t 0.025 ^b 35.9 :t 3.2 38.8 :t1. 8 0 .1 19 :t 0.004 0.043 :t 0.009 0.059 :t 0.029 0.009 :t 0.004 2.523 :t 0.287 0 .3 17 :t 0.078 0.218 :t 0.061 34.5 :t 3.0 35.7 :t 0.8 0.112 :t 0.0 1O 0.043 :t 0.004 0.084 :t 0.012 0.005 :t 0.001 2 .1 44 :t 0.211 0 .3 64 :t 0.026 0괴5 :t 0.031

34.5 :t 2 .4 37.7 :t 2 .4 0 .1 17 :t 0.012 0.042 :t 0.001 0.073 :t 0.013 0.005 :t 0.002 2 .1 07 :t 0.263 0 .3 90 :t 0.035 0 .1 60 :t 0.019 34.9 :t 2.6 37 .4:t 2 .1 0 .1 16 :t 0.009 0.043 :t 0.006 0.072 :t 0.021 0.006 :t 0.003 2.258 :t 0.298 0 .3 57 :t 0.058 0 .1 78 :t 0.049 ^a

a.b D ifferent superscripts within same columns are significantly differ , P(0.05.

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Table 4. Effect of DM and DEHP administration a month on body weight and organ weight

Day Body weight(g) ürgan weight(g)

after Treat

last nitial final Testis Epididymis '.. Vasicular Coagulatin ---0-._.... Li ver Kidney Spleen lnjection ... _. - -_ .. - ^~ .... _._" .... - gland gland

34.5 :t 4.5 37.3 :t 0.5 0 ^.1 23 :t 0.013 0.045 :t 0.001 0.081 :t 0.012 0.005 :t 0.002 2.095 :t 0 ^.1 67 0.320 :t 0.024 0 ^.1 30 :t 0.031 Con. 3 34.5 :t 2.6 36.3 :t 2.8 0.290 :t 0.396 0.046 :t 0.004 0.080 :t 0.007 0.006 :t 0.002 2 .1 29 :t 0.268 0.387 :t 0.014 0 .1 32 :t 0.006 5 34 .4:t1. 2 37.2 :t 3.5 0 ^.1 24 :t 0.024 0.047 :t 0.004 0.097 :t 0.028 0.005 :t 0.001 1. 939 :t 0.265 0.345 :t 0.029 0 ^.1 20 :t 0.047 Mean 34 .4:t 2.6 36.9 :t 2.3 0 .1 79 ^::1: 0.230 0.046 :t 0.004 0.086 :t 0.021 0.005 :t 0.001 1. 994 :t 0 .1 99 ^b 0 .3 36 :t 0.032 0 .1 18 :t 0.031 ^b

34 .5:t 4 ^.1 35 .3:t 2.9 0 ^.1 12 :t 0.010 0.040 :t 0.005 0.090 :t 0.020 0.005 :t 0.000 1. 981 :t 0 ^.1 33 0 .3 57 :t 0.024 0 ^.1 21 :t 0.035 3 34.3 :t 2.0 38.0 :t3. 5 0 .1 25 :t 0.003 0.043 :t 0.004 0.080 :t 0.007 0.006 :t 0.002 2 .1 29 :t 0.268 0.387 :t 0.014 0 .1 32 :t 0.006 5 34.8 :t1. 7 36.7 :t1. 0 0 .1 16 :t 0.024 0.044 :t 0.004 0 .1 59 :t 0 .1 93 0.005 :t 0.002 1.1 91 :t 0.232 0.366 :t 0.009 0 .1 50 :t 0.065 34 .5:t 2.5 34.7 :t 2.6 O .l 17 :t 0. 0l 5 0.042 :t 0.004 0 .1 10 :t 0 .1 11 0.005 :t 0.002 2. 0l 0 :t 0.211 ^b 0.370 :t 0.020 0 .1 34 :t 0.039 ^a 34.6 :t 3.3 4 1.3:t1. 0 0 .1 16 :t 0.020 0.042 :t 0.004 0.080 :t 0.026 0.005 :t 0.0 0l 2.382 :t 0 .1 40 0 .4 11 :t 0.065 0 .1 82 :t 0.025 3 34.7 :t1. 9 40.8 :t 0.6 0 .1 17 :t 0.038 0.042 :t 0.017 0 .1 58 :t 0 .1 51 0.008 :t 0.002 2.280 :t 0 .1 36 0.359 :t 0.036 0 .1 56 :t 0.034 5 34.5 :tl.l 38.7 :t3. 8 0 ^.1 16 :t 0.009 0.044 :t 0.002 0.064 :t 0. ^0l 5 0.006 :t 0.002 2.329 :t 0 .5 34 0.343 :t 0.038 0 ^.1 56 :t 0.005 DM

Mean

뻐

p

Mean 34.6 :t 2.0 40.3 :t 2.3 0 ^.1 17 :t 0.024 0.043 :t 0.009 0 ^.1 00 :t 0.094 0.006 :t 0.002 2.331 :t 0.288 ^a 0 .3 71 :t 0.054 0 ^.1 65 :t 0.025 ^a

a.b D ifferent superscripts within same columns are significantly differ , P<O.05.

ill.

본 실험의 결과 정액성상검사에서 총청자 수 검사결과를 보면 DM과

DEHP

26 .7:1: 13 .3, 2 1. 7 :1:

52.5 :1:

1 1.8보다 유의적으로 낮게 나타났고 (P<0.05)

,

DEHP

19.0 ^:1: 7.8 ^, 19 ^.1

4 1. 7 ^:1:

P<0.05L

유효정자수에서도 15 일후 검사결과 DM과

DEHP

1 1. 7 :1: 8.5 ,

39.7 ^:1:

12.3 :1: 6 .1, 16 .4:1:

7.0으로

44 ^.4:1:

DEHP

20.6 :1: 7.2 ^, 24.0 ^:1:

검사결과도

25.2 ^:1: 7.0 ^, 26.0 ^:1:

16.7

(P<0.05).

1989) D ema

그러나 DM과

DEHP

Thomas(

100.0mg

장기무게에 있어서는 간， 신장， 비장의 무

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동:물자원연구 (2000)

게의 경우 15 일후 검사결과

DEHP

0 .1 78 :t

DEHP

투여구가

2 .3 31 :t

DEHP

0 .1 34 :t 0.039 ,

약 40년 전부터 morphinan으로 널리 사용 된 DM은 기침약의 성분으로 쓰이고 있지만 구토， 둔감， 비뇨기증상， 무감각， 안구진탕，

혼수상태등의 증상이 나타나기도 하는데 (William등，

1977) ,

peroxisome

을 증식시키며 간암을 유발하고， 특히 미극 에서는 암 유발물질로 분리하고 있다 (Busser 와 Lutx등，

198 7).

본 실험의 결과 DM과 DEHP의 단기간과 장기간의 투여는 정액성상에는 유해한 영향 을 미쳤으나， 장기무게에는 커다란 영향을 미치지 않은 것으로 나타났다.

N.

본 실험은 내분비계 장애물질 중 관찰물질로 지정된 DEHP와 기침약에 이용되는 DM 을 15 일과 29 일동안 투여가 생쥐의 정액성상과 장기무게에 미치는 영향을

1. 3 ,

1.

DEHP

투여 후 검사결과를 보면

DM

26 .7 x 10 ⁶ / ml , D EHP

2 1. 7 x 10 ⁶ /

ml

52 .5 X 10 ⁶ /

DM

19.0 x 10 ⁶ / ml , D EHP

19 .1 x 10 ⁶ /

4 1. 7 x 10 ⁶ /

의하게 낮은 성적을 나타났 (P<0.05L

2.

DEHP

DM

1 1. 7% ,

DEHP

39.7% 에 비해 유의적으로 낮은 성적을 나 타냈으며 (P(0.05) ， 29 일 투여후 검사결과 도

DM

12.3% , DEHP

3.

DEHP

DM

20.6% , DEHP

DM

투여구는

25.2% , DEHP

26.0%

로서 대조구 16.7% 에 비해 유의적으로 높 은 성적을 나타냈다 (P(0.05).

4.

5.

DM

DEHP

무게는 투여구간에 커다란 차이가 인정되 지 않았지만，

DEHP

0 .1 78g

0 .1 15g , DM

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무게는 커다란 차이가 인정되지 않았지만，

간의 무게에 있어서

DEHP

1. 994g. DM

DM

O .l 34g. D E HP

v.

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