' T R A C E ' ~:"' I O N

F A I L U R E OF INDOMETHACIN I N .... L : M I T I N G E B R T I L I Z I N G ...... CAPAC TY OF THE E P : I D I D Y L S P E R TOZ

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ABSTRACT

Surgical separation of epididy des :from the: testes ..... a the est s-cap~t~ junction re ai ed the "fert2lizing capacitY' of the confinea spermatozoa up to three weeks .......... ever mating with these an reals four weeks following the surgica! manipulation proved to be consistently,,in£erti e, CNronic t yea tmen t o f fndome t hacin a t a dos e o f Z. 5 mg/kg bw on al t, er nate days beginningu on the day of ...... evation resulted in r e- g ~- e s s i o n Q r t e ~ t i c : a r we i g h t ( p < 0 o p i ?, t h o u g h t h e e e r t i:: z: ng capaci y, of tl~e ep~didymai spermatozoa was inaintained as good a found in controls,

ccepted for publication August 1:9, 1976

T h e e x p e n s e s , o f t h i s i n v e s t i g a t i o : n , w e r e c l e f r a K e d b y research grants ...... o ..... ::a:l

Z~ ti on Human Repr0~uc tio p i i e s

O C T O B 13[ 1 9 7 6 " L . ......... ~ LNO. ¸̧ :̧5̧ ̧

C O N " I R O N

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1 'hough t h e o c c u r r e n c e o f p r o s t a g l a n d i n s in - t t l e m a l e a c c e s s o r i e s i s c o n s i s t e n t , i t s i o l o g i c a l f u n c t i o n i n male fertility is obsc re ..... Und ed human infertiTi"ty has b e e n f o n d t o - b e a s s o c i a t e d w i t h a l t e r e d , c o n c e n t r a t i o a s o f s e m i n a l p r o s t a g l a n d i h E ( P G E ) a n d p r o s t a g l a n d i n F ( P G F ) v a r i e t i e s ( i , 2 ) . T h e mo t i i i t >" o f h urea n s p e r m a t o z o a h a s b e e n r e c o r d e d t o . b e . i n f i u e n c e d b y t h e a d d i t i o n o f P G F 2 a ( 3 ) , PGs h a v e b e e n i d e n t i f i e d i n t h e t e s t i s e p i d i d y m i s , d u c t u s d e f e r e n s and other accessory sex glands in" rats (4, 5) and its sugges- tive r o l e i n r e g u l a t i n g t e s t i c u l a r c o n t r a c t i o n ( 6 ) , t e s t o s t e r o n e biosynthesis in. rats and mice (7, 8, 9) and sp:er~atoge~sis in r a t s ( 1 0 ) h a v e b e e n d o c u m e n t e d . T h e c o l l . ~ c r i v e d a t a o f t h e present investigatio11 reveal that a c~ronic application of indomethac~n, a specific inhihi tot of i, Gs biosynthesi s ) c o n s i s t e n t l y . f a i l s t o I i m i t t h e f e r t i l i z i n g c a p a c i t y o f t h e c o n f i n e d e p i d l d > a l s p e r m a t o z o a

r ER I AL S AN D METHODS

Lab o r a t o ry b r e d a i e a I b i no r a t s o p r o v e :n. f e r t i I i t Were housed at a controlled lighting schedule of 12 h light p e r ..... d a y a n d h a d f r e e a c c e s s t o p e l l e t e d f o o d a n d w a t e r , I n d o -

e t h a ¢ i n ( 1 - ( p .... ¢ h i o r o b e n z o x y I ) S - m e t h o x y - Z - m e t h y I i n d o I .... 3 a c e t i c a c i d ) , an e s t a b i i s h e d i n h i b i t o r o f PGs s y n t h e t a s e a c t i v i t - ) , ( I t ) , k i n d l y d o n a t e d by M e r c k I n s t i t u t e f o r T h e r a , - peutic Research, New Jersey, was dissolved i-n corn. oi! and i n j e c t e d s c a t . a d o s e l e v e l o f 2 . 5 bw o n a l t e r n a t e d a y s a s p e r t e s c h e d u i e ( T a b i e 1) ...... Ep i i d e s o f t h e , an ma l s w e r e .... s u r g i c a l l y s e p a l ' a r e a l u n d e r t g h t e t h e r a n e s t h e s a t t h e t e s t i s c a p u t j u n c t i o n t a k i n g c a r e t o l e a v e t h e b l o o d v a s - c u i a t u r e s u p p l y i n g t h e t e s t ~ s a n d e p i d i d y m i s i n t a c t .... C y c l i c f e m a ! e s o n t h e a y o f t h e i r v a g i n a l r o e s t r u s w e r e p a i r e d overnight ith the test ani~ais. Presence o:f spermatoz a in the e t r o u s v a g i n a l .... s m e a r o r v a i n a l p l u g s w a s c o n s i d e r e d .... a s a n i n d e x o £ d a y 1 o f p r e g n a n c y On d a y 8 p , c . , I a p a r o t y w a s p e r f o r m e d o n t h e m a t e d f e m a l e s t o r e d o n f i r m p r e g n a n c y b y locating the presence of implantati n site(s). Animals were sacrificed 30 days following the surgical ma ipulation of the e p ~ d i d y m i s . A t a u t o p s y , .... t e s t e s , ' e p i d i d y m i ~ e s , s e m i n a i vesicles,: prostates and c0agulating glands were removed:, freed of t h i r m d h e r i n g t i s s . u e , w e i g h e d o n a ..... t o r s i o n b a t a n c e a n d compared With the controls using Student'..s. "t" test o

RESU LT S D D I S CUS S ! ON

T h e f e r t i I i z i n g c a p a c i , t y o f i t h e c o n f i n e d . e p i d i d y m a 1 spermatozoa- was found : :to be. :for flow- ing the ........ surgical :separation'of/:epididzmides .... at.:the te tis- " caput j unction. Nazlng. With these ~animil S Was ~ found to :be for t i I e ..... anyt ~me during the fir s t ,- s e cond o r ~h i~d ek fol 1 owing the ..... surgical manipulat on, HoweVer, ~ a t i n g , he fourth week was ze co rd ed .... to be ertl i e but ~a d e the ~ fema le pseudo pre gn an t, an indi c a t on o g k e ep i n~ s exua i- ,, a c t iv i ty o f t he

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CONTRACE I

animals intact without retaining t h e potential fertilizing capacity of the epididymal spermatozoa. A chronic treatment of indomethacin on alternate days beginning on the day of surgical procedure was recorded to retain male fertility as usual up to the third week; however, the testicular weight was significantly lowered (P<0.01). The PGs appear to be involved in LH release (12), since indomethacin induces deficiency of endogenous LH (13). The regression of testi- cular weight with concurrent maintenance of the weight of other accessory glands [Table II) as recorded in the ~ present experiment is rather a puzzling question. The tendency of testicular regression, as generally observed after the dis- ruption of the intimacy between the testis and epididymis (14), may possibly sensitize the testicular tissue to Se: more reactive to any slight change in plasma LH levels or to the direct effect of indomethacin.

When PGs are identified in testis, epididymis and other ;=ccessory reproductive glands in rats (4, S), its presence :aight have some significant role(s) in the regulation of p o t e n t i a l f e r t i l i t y . H o w e v e r , f a i l u r e o f i n d o m e t h a c i n , i n limiting the fertilizing capacity of the limited epidid al spermatozoa as recorded in the present study, is ratchet enigmatic, but confirms the findings of Saksena e a . (13).

A C K N O W L E D G E M E N T S

The encouraging cooperation of Dr. Dr. S.J. Segal, Dr. R.~. Mahoney, Dr. A. Spieler is gratefully acknowledged.

(Mrs.) Sabita Tejuja, Bartke and Dr. J.M

d a t a Sincere cooperation of Mr. is greatly appreciated

B.S. Paul in analyzing the

R E F E R E N C E S

Bygdeman, M. , Fredricsson, B., Svanborg, and S amuelsson, B.- The .... relation between fertiiity ~and prostagla din content .... of Seminai fluid in man. Fertil ....... S t e r i l .... 2 1 6 2 2 ( 1 9 7 0 ) .....

t

t

Brummer, H G. and ..... fertility

a n d G i I Ies p i e, A. " Sem i na I pro s t a g I and i n s C l i n .... E n d o c r . 1 3 6 5 ( 1 9 7 2 ) ....

E s k i n , B . A . , .... A z a r b a l , S . , S e p i c , R ..... .... . . . . . . . - .......... and .... tare, ~.G. In vitro esponses of spermat?zo-cervical mucus system

ea~ ith pros landin F2a). ~Obstet Gvnec. N.Y ..... 4 1 3 6 ......... 9 7 3 )

Carpenter, M*P., Manning, L. and Wiseman, B .... : Prosta- gland synthesi in rat ....... testis ..... .... Fed. .... Proc .......... e ...., Soc E ~ , . 1 : 1 0 8 Ab r ......... (1.o 1.) ,

O C T O B E R 1976 VOL. 1 4 NO. 4 469'

C O N T R A C E I O N

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Tan, N.C. and Privett, O.S." i n h e r a t v e s i c u i a r g l a n d s .

An a I y s i s o f p r o s t a g I an d i n s L i p i d s 7 " 6 2 Z ( 1 9 7 2 ) .

Hargrove, J.L., Johnson, J.M and Ell is, L.C. : Prosta- glandin E~-induced inhibition of rabbit testicular contractions i vitr . Proc. Soc. Exp. Biol. Ned. [36: 958 (1971).

B a r t k e , A . , s t o , N. , C a l d w e l l , B . V . a n d B e h r m a n , . ~ i . R . - Effects of a cholesterol esterase inhibitor and of prostaglandin F2a-on testis cholesterol and on plasma testosterone in mice. Prostaglandins 3-97 ( 1 9 7 3 ) .

Saksena, S.K., E1 Safoury, S. and Bartke, A.- Prosta- glandin Ez and F z ~ decrease plasma testosterone levels in male rats. Pros tagland ins 4-235 (1975).

Saksena, S.K., Lau, I.F. and Bartke, A.- Prostaglandin A~ and A2 decrease testosterone levels in mlce and rats. Endocrinology 95-311 (1974).

Ericsson, R.J.- in the male rat.

Prostaglandins Adv Biosci.

(E~ and E2) and reproduction 9" 7 3 7 (1973) .

Vane, J.R.- Inhibition o f prostaglandin synthesis as a mechanism of action of aspirin-like drugs. Nature. New Biol. 231-232 (1971).

Ojeda, S.R., Harm~, P.G. and McCann, S.M.- Effect of third v e n t r i c a l i n j e c t i o n s o f p r o s t a g l a n d i n s ( P G s ) o n g o n a d o - t r o p i n r e l e a s e i n c o n s c i o u s f r e e m o v i n g m a l e r a t s . P r o s t a g l a n d i n s 8 - 5 4 5 ( 1 9 7 4 ) .

S a k s e n a , S . K . , L a u , I F . , B a r t k e , A . a n d C h a n g , M . C . : E f f e c t o f i n d o m e t h a c i n o n b l o o d p l a s m a l e v e l s o f LH a n d testosterone in male rats. J. Reprod. Fert 42"311 (197S).

Harrison, R G " The effect of ligation of vasa efferentia on the rat testis ..... Proc Soc Study Fertility 5-97

9 s 3 ) .

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