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Postcoital Prostaglandins, in Vivo Oviductal Motility, and Egg Transport in Rabbits *
Vol. 24, No.9, September 1973
FERTILITY AND STERILITY
Copyright © 1973 by The Williams & Wilkins Co.
Printed in U.S.A.
POSTCOITAL PROSTAGLANDINS, IN VIVO OVIDUCTAL MOTILITY, AND EGG TRANSPORT IN RABBITS* 1. AREF,t E. S. E. HAFEZ,
AND
G. A. R. KAMAR*
Departments of Gynecology-Obstetrics and Physiology, and the C. S. Matt Center for Human Growth and Development, Wayne State University, School of Medicine, Detroit, Michigan 48201
.
Prostaglandins, oxytocin, nicotine, epinephrine, norepinephrine, a adrenergic blockers and stimulators, and (3 adrenergic blockers and stimulators have been used to study the physiopharmacology of oviductal motility in vivo in women, monkeys, and rabbits. 1-5 Egg transport through the oviduct depends primarily on the contractility of the musculature, which, under the influence of ovarian hormones,6 undergoes definite cyclic variations. 7 Theoretically, the endocrine environment may also affect nerve endings located at the ampullary isthmic junction which in tum affects the patterns of contraction and egg transport. The formation and release of prostaglandins may be brought about by these nerve endings; however, seminal plasma contains large quantities of prostaglandins. Although total seminal plasma prostaglandins are systemically absorbed by the vaginal mucosa, the concentration achieved is too low to affect the motility of the oviduct. 8 Systemic and local administration of isolated prostaglandins, however, evokes remarkable changes in oviductal contractility. Prostaglandin F stimulates and prostaReceived January 29, 1973. • Contribution 47 from the International Postdoctoral Training Program in Physiology of Reproduction. Supported by Ford Foundation Grant 710-0287 and National Institute of Child Health and Human Development Grant HD 02634-02. t Present address: Max Planck-Institut fUr Immunobiologie, Freiburg 8, West Germany. * Present address: Division of Animal Reproduction, Cairo University, Cairo, Egypt.
glandin E inhibits oviductal motility in vivo. The antithetic effects of prostaglandins F (PGF) and E (PGE) on the oviductal musculature would explain the controlled transport of gametes in opposite directions through the reproductive tract. The implication of such effects for egg transport deserves intensive study and may be of clinical significance for contraceptive purposes. The purpose of this experiment was to study the effects of PGE 2 and PGF 2a on the rate of egg transport, the oviductal intraluminal pressure variations in vivo, and the correlation between rate of egg transport in one oviduct and the pattern of contractility on the contralateral side. MATERIALS AND METHODS
Adult female New Zealand rabbits weighing 3-4 kg. were used. Through a flank laparotomy, a microballoon was gently pushed through the abdominal ostium of the oviduct to the ampullary isthmic junction. 9 The free ends of catheters were exteriorized and fixed to the skin on the backs of the animals. The flank incision was used to minimize trauma and postoperative adhesions to the reproductive organs of the contralateral side. To record oviductal motility, the catheters were flushed to eliminate air bubbles, filled completely with fluid, and connected to a pressure transducer (Sanborn 267, B.C.), a carrier preamplifier (Sanborn 350, 1l00C), and a Hewlett-Packard 7700 recorder. On the third postoperative day the does
671
672
AREF ET AL.
were mated to two fertile bucks; the vagina was swabbed and the smear was examined microscopically for the presence of spermatozoa. Chorionic gonadotropins (25 LU.) were injected intravenously. At 24 hr. postcoitum (PC), oviductal motility in eight rabbits was monitored every 2 hr. for 12 hr. Rabbits were autopsied at 48 hr. PC and the unmonitored oviduct was carefully freed from the adjoining fat, separated from the uterine hom, and then divided into four equal segments; each segment of the oviduct and the uterus was flushed separately, and the flushings were examined under a stereomicroscope for the presence of ova. In 16 rabbits, oviductal motility was monitored at 24 hr. PC, every 2 hr. for 12 hr. before and after subcutaneous injection of 3 or 12 mg. of PGF 2a or PGE 2 dissolved in 1 m!. of physiologic saline. The rabbits were autopsied 48 hr. PC and the oviducts were divided and flushed. This experiment was performed to study the effects of different doses of PGF 2a or PGE 2 on oviductal motility and egg transport. One dose of 6 mg. of PGF 2a was administered at 12 hr. PC to five rabbits and at 24 hr. PC to five others. Oviductal motility was monitored every 2 hr. for 12 hr. before and after injection. At 36 hr. PC, autopsy and segmental flushings were carried out. This experiment was performed to study the effect of 6 mg. of PGF 2", injected at different intervals postcoitum, on oviductal motility and egg transport. RESULTS
Oviductal Motility. At 24 hr. PC, oviductal motility was monitored in eight untreated rabbits every 2 hr. The periods of recording per rabbit varied between 60 and 120 min. Oviductal motility was stimulated following the injection of 12 mg. of PGF 2a (Fig. lA). A latent period of 15-20 min. was followed by a gradual increase in motility.
Vol. 24
Two hours following injection, there was a remarkable increase in the amplitude and duration of contractions. The stimulated pattern was recorded at 4, 6, 8, and 10 hr. after injection. Twelve hours after PGF 2a administration, the motility returned to its initial pattern. When one dose of 3 mg. of PGF 2a was injected 24 hr. PC, a stimulated pattern was observed 2-2.5 hr. following the injection, and it lasted for 3-4 hr. The amplitude and duration of contractions were considerably less than those observed following injection of 12 mg. The effectiveness of PGF 2a in stimulating oviductal contractility was most remarkable following the subcutaneous injection of 12 mg.; it was minimal when the dose was 3 mg., and intermediate following 6 mg. The response of the oviduct following the injection of 6 mg. ofPGF 2a at 12 hr. PC was similar to its response when the same dose was injected 24 hr. PC. Oviductal motility was initially inhibited following PGE 2 injection (Fig. IE). When one dose of 12 mg. of tlGE 2 was administered 24 hr. PC, a latent period of 10-15 min. was followed by a gradual decrease in the motility and a remarkable decrease in the amplitude of contraction for 3-4 hr. The motility returned to its initial level 4.5-5 hr. after the injection, which was followed by secondary stimulation for 2-3 hr. The motility finally returned to the initial level 8-10 hr. after injection. When one dose of 3 mg. of PGE 2 was injected 24 hr. PC, an inhibited pattern was observed following a latent period of 20-30 min. This inhibition was observed for 1-2 hr. and a compensatory stimulation was noted for 30-60 min. Egg Transport. In untreated rabbits, 89% of eggs were recovered from the third segment of the oviduct and no eggs were recovered from the uteri at 48 hr. PC. When one dose of 12 mg. of PGF 2" was injected 24 hr. PC, 63% of eggs were recovered from the fourth segment of the ovi-
.
September 1973
673
IN VIVO OVIDUCTAL MOTILITY
A
B
:_11
Hrs. after inj. 2
4
6
o 25
8
o 25
12
o MINUTES
>-
.>
,.
MINUTES
FIG. 1. Oviductal motility in vivo in rabbits. A, following one dose of 12 mg. of prostaglandin F' a injected subcutaneously 24 hr. postcoitum. Note that the stimulated oviductal motility returned to its initial pattern 12 hr. after injection; B, following one dose of 12 mg. of prostaglandin E. injected subcutaneously 24 hr. post· coitum. Note that oviductal motility was primarily inhibited for 4 hr., secondarily stimulated 8 hr. after the injection, then returned to its initial level 12 hr. after the injection.
ducts 48 hr. PC and 36% from the uteri. When one dose of 3 mg. of PGF 2a was injected, 33 and 62% of eggs were recovered from the third and fourth segments of the oviducts, respectively, and 4% were recov· ered from the uteri. When 6 mg. of PGF 2a were injected 24 hr. PC, 47% of eggs were recovered from the fourth segment of the oviducts 36 hr. PC and 4% from the uteri. However, when PGF 2a was injected 12 hr. PC, 8% of eggs were recovered from the fourth segment of the oviducts and no eggs were recovered from the uteri. When 3 or 12 mg. of PGE 2 were injected 24 hr. PC, a slight disturbance in egg transport was observed, and no eggs were recovered from the uterus at 48 hr. PC. At 48 hr. PC, the percentage of egg recovery in PGF 2a-treated rabbits was less than that
in PGE 2-treated and untreated rabbits. In PGF 2a -treated rabbits, the percentage of eggs recovered 36 hr. PC was higher than the percentage of recovery 48 hr. PC. It is assumed that unrecovered eggs were expelled from the genital tract. At 48 hr. PC, 10 eggs were recovered from the uteri of PGF 2a-treated rabbits; four were unfertilized and six were at the 16- to 32-cell stage. No eggs were recovered from the uteri of PGE 2-treated or untreated rabbits (Fig. 2). DISCUSSION
Functionally, the oviduct is divided into various segments, each of which exhibits an independence evidenced by the asynchronous appearance of outbursts of increased activity in the varied segments. In
674
Vol. 24
AREF ET AL.
FLUSHED EGGS
••••
••••
•• •••• ••••
• •••
•••• ••••
• •• •••• • •••
••••
,..
Control ••••• ••
Minutes
•• •• •••• ••••
Segments
~'= Uterus UTJ 4
3
~"""""" 2
1
FIG. 2. Egg transport and oviductal motility in rabbits as affected by a single dose of 12 mg. of prostaglandin F 2. (PGF ..) or prostaglandin E2 (PGEJ subcutaneously injected 24 hr. postcoitum. Oviductal motility was recorded in vivo in one oviduct at 2 and 8 hr. following prostaglandin injection. Eggs were recovered from the contralateral side by segmental flushing. Note that PGF •• was effective only in hastening egg transport. Oviductal motility was stimulated in response to PGF 2a injection. PGE. injection caused an initial inhibition followed by secondary stimulation 8 hr. after injection. UTJ, utero-tubal junction.
the rabbit, these outbursts were characterized by sets of intense muscular contractions and a gradual increase in the intraluminal pressure, followed by a decrease in the intensity of the contractions and a lowering of intraluminal pressure. This pattern may suggest the overcoming of a distal antagonism, which, when yielded, resulted in the lowering of the intraluminal
tension and expulsion of the contents further to the distal segment. The mechanism of retention of ova at the ampullary isthmic junction is of considerable importance in timing egg transport through the oviduct. Strong oviductal contractions could prematurely expel the eggs to the uterus and terminate pregnancy. Prostaglandins exert remarkable effects
September 1973
•
>
IN VIVO OVIDUCTAL MOTILITY
675
on the contractility of the oviduct in vivo. taneously increased the oviductal motility In rabbits, local instillation of 0.4 mg. of for 8-12 hr. and effectively hastened egg PGE 1 in the oviduct induced an immediate transport when injected 24 hr. PC. The paralyzing effect for 3-5 min. The contrac- effectiveness of PGF 2a in stimulating ovitions returned gradually to the initial level ductal motility was independent of the within 5-20 min. The contractions of the reproductive phase. PGF 2a stimulated ovisame oviduct increased 5-7 hr. following ductal motility when injected 12 or 24 hr. the injection of 2.4 mg. and reached a PC. However, its effectiveness in hastening maximal level after 9-14 hr.lO Spilman egg transport was remarkable when inand Harper 5 reported a large decrease in jected 24 hr. PC and was partial when the basic tone and a decrease in the frequency same dose was injected 12 hr. PC. lt is possible that the effectiveness of for 7 min. following intravenous administration of PGE I or PGE 2 • PGF I at doses of PGF 2a in hastening egg transport could 50, 100, or 200 p,g. intravenously evoked only be elicited during a specific phase of a sustained increase in the tone which the reproductive cycle. The intensity ofthe lasted 5.5 min. The subcutaneous injection contractile response of the oviduct followof PGE 2 (0.5-1.5 mg.) suppressed ovi- ing prostaglandin injection, however, deductal activity for. 20-40 min., whereas pends upon the dose administered. The PGF 2a (7.5 mg.) increased the frequency presence of 16- to 32-cell stage morulae in and amplitude of contractions for 1-1.5 hr. the uteri of PGF 2a-treated rabbits 48 hr. A stimulatory response was observed in PC provided evidence that egg transport women following the injection of 100 ILg. through the oviducts was hastened. of PGF 2a intravenously. Injection of 100 Further studies are needed to determine p,g. of PGE 2 , however, was followed by the fate of these rapidly transported eggs. Interference with implantation and/or coninhibition. 2 In the rabbit, 5 mg. of PGE 1 and PGF 2a ception will determine the future use of subcutaneously hastened the transport of prostaglandin F 2a as a possible postcoital the eggs to the uterus by approximately 40 contraceptive. hr. II Following subcutaneous injection of PGF 2a (5 mg./kg.), no eggs were recovered SUMMARY from the oviduct and few eggs were recovered from the uterus. 12 Following the injecProstaglandins F 2" and E2 (3, 6, and 12 tion of PGE 1 (5 mg./kg.) subcutaneously, mg.) were subcutaneously administered egg transport was partially hastened, but to rabbits at 12 and 24 hr. PC. In vivo PGE 2 was ineffective in altering the rate oviductal motility was monitored in one of egg transport in the rabbit oviduct. oviduct and egg transport was studied on In this study, subcutaneous injection of the contralateral side. PGF 2a effectively 12 mg. of PGE 2 inhibited the contractility hastened egg transport when injected 24 for 4-5 hr. Six hours after its injection, the hr. PC and its effect was less remarkable motility returned to the initial pattern, and when injected 12 hr. PC. The effectiveness a secondary stimulation was gradually es- of PGF 2<> in stimulating oviductal motility tablished. The ineffectiveness of PGE 2 in and in hastening egg transport was higher delaying egg transport through the oviduct when the dose injected at 24 hr. PC was could be attributed to its short duration of increased from 3 to 12 mg. The subcutaneaction and to the compensatory secondary ous administration of PGE 2 at 24 hr. PC stimulation 8 hr. following its injection. On was ineffective in altering egg transport, the other hand, 12 mg. of PGF 2a subcu- and its primary inhibitory effects on ovi-
676
AREF ET AL.
ductal motility were compensated by delayed stimulation. Acknowledgments. The authors gratefully acknowledge Dr. Kazuo Sano of ONO Pharmaceutical Co., Osaka, Japan, for providing the prostaglandins; and Ayerst Laboratories, Inc., New York, for providing human chorionic gonadotropins.
6.
7.
8.
REFERENCES 1. COUTINHO, E. M., AND MAlA, H. S. The influence of the ovarian steroids on the response of the human fallopian tube to neurohypophyseal hormones in vivo. Amer J Obstet Gynec 108:194, 1970. 2. COUTINHO, E. M., AND MAlA, H. S. The contractile response of the human uterus, fallopian tubes, and ovary to prostaglandins in vivo. Fertil Steril 22:539, 1971. 3. COUTINHO, E. M., MAlA, H., AND ADEODATO FILHO, J. Response of the human fallopian tube to adrenergic stimulation. Fertil Steril21 :590, 1970. 4. NERI, A., AND MARCUS, S. L. Effect of nicotine on the motility of the oviducts in the rhesus monkey: A preliminary report. J Reprod FertiI31:91, 1972. 5. SPILMAN, C. H., AND HARPER, M. J. K. Effect of
9.
10.
11.
12.
Vol. 24
prostaglandins on oviduct motility in conscious rabbits. Bioi Reprod 7:106, 1972. BOLING, J. L. "The Endocrinology of the Oviduct." In Pathways to Conception, Sherman, A. I., Ed. Thomas, Springfield, Ill., 1971. AREF, I., AND HAFEZ, E. S. E. Cyclical changes in utero-oviductal motility in the rabbit. J Reprod Fertil 32:92, 1973. HORTON, E. W., MAIN, I. H. M., AND THOMPSON, C. J. Effects of prostaglandins on the oviduct, studied in rabbits and ewes. J Physiol (London) 180:514, 1965. AREF, I., AND HAFEZ, E. S. E. Utero-oviductal motility with emphasis on egg transport. Gynec Obstet Survey, 1973. In press. SALOMY, M., AND HALBRECHT, I. "Immediate and Late Effect of PGE, on the Rabbit Oviduct (In Vivo Studies)." In Proceedings of the International Conference on Prostaglandins, Vienna. Pergamon Press, New York, 1972. ELLINGER, J. V., AND KIRTON, K. T. Ovum transport in rabbits injected with prostaglandin E, or F2a • Bioi Reprod 7:106, 1972. CHANG, M. C., AND HUNT, D. M. "Effects of Prostaglandins on the Transportation of Rabbit Eggs and Spermatozoa." In Proceedings of the International Conference on Prostaglandins, Vienna. Pergamon Press, New York, 1972.
~1
FERTILITY AND STERILITY
Copyright © 1973 by The Williams & Wilkins Co.
Printed in U.S.A.
POSTCOITAL PROSTAGLANDINS, IN VIVO OVIDUCTAL MOTILITY, AND EGG TRANSPORT IN RABBITS* 1. AREF,t E. S. E. HAFEZ,
AND
G. A. R. KAMAR*
Departments of Gynecology-Obstetrics and Physiology, and the C. S. Matt Center for Human Growth and Development, Wayne State University, School of Medicine, Detroit, Michigan 48201
.
Prostaglandins, oxytocin, nicotine, epinephrine, norepinephrine, a adrenergic blockers and stimulators, and (3 adrenergic blockers and stimulators have been used to study the physiopharmacology of oviductal motility in vivo in women, monkeys, and rabbits. 1-5 Egg transport through the oviduct depends primarily on the contractility of the musculature, which, under the influence of ovarian hormones,6 undergoes definite cyclic variations. 7 Theoretically, the endocrine environment may also affect nerve endings located at the ampullary isthmic junction which in tum affects the patterns of contraction and egg transport. The formation and release of prostaglandins may be brought about by these nerve endings; however, seminal plasma contains large quantities of prostaglandins. Although total seminal plasma prostaglandins are systemically absorbed by the vaginal mucosa, the concentration achieved is too low to affect the motility of the oviduct. 8 Systemic and local administration of isolated prostaglandins, however, evokes remarkable changes in oviductal contractility. Prostaglandin F stimulates and prostaReceived January 29, 1973. • Contribution 47 from the International Postdoctoral Training Program in Physiology of Reproduction. Supported by Ford Foundation Grant 710-0287 and National Institute of Child Health and Human Development Grant HD 02634-02. t Present address: Max Planck-Institut fUr Immunobiologie, Freiburg 8, West Germany. * Present address: Division of Animal Reproduction, Cairo University, Cairo, Egypt.
glandin E inhibits oviductal motility in vivo. The antithetic effects of prostaglandins F (PGF) and E (PGE) on the oviductal musculature would explain the controlled transport of gametes in opposite directions through the reproductive tract. The implication of such effects for egg transport deserves intensive study and may be of clinical significance for contraceptive purposes. The purpose of this experiment was to study the effects of PGE 2 and PGF 2a on the rate of egg transport, the oviductal intraluminal pressure variations in vivo, and the correlation between rate of egg transport in one oviduct and the pattern of contractility on the contralateral side. MATERIALS AND METHODS
Adult female New Zealand rabbits weighing 3-4 kg. were used. Through a flank laparotomy, a microballoon was gently pushed through the abdominal ostium of the oviduct to the ampullary isthmic junction. 9 The free ends of catheters were exteriorized and fixed to the skin on the backs of the animals. The flank incision was used to minimize trauma and postoperative adhesions to the reproductive organs of the contralateral side. To record oviductal motility, the catheters were flushed to eliminate air bubbles, filled completely with fluid, and connected to a pressure transducer (Sanborn 267, B.C.), a carrier preamplifier (Sanborn 350, 1l00C), and a Hewlett-Packard 7700 recorder. On the third postoperative day the does
671
672
AREF ET AL.
were mated to two fertile bucks; the vagina was swabbed and the smear was examined microscopically for the presence of spermatozoa. Chorionic gonadotropins (25 LU.) were injected intravenously. At 24 hr. postcoitum (PC), oviductal motility in eight rabbits was monitored every 2 hr. for 12 hr. Rabbits were autopsied at 48 hr. PC and the unmonitored oviduct was carefully freed from the adjoining fat, separated from the uterine hom, and then divided into four equal segments; each segment of the oviduct and the uterus was flushed separately, and the flushings were examined under a stereomicroscope for the presence of ova. In 16 rabbits, oviductal motility was monitored at 24 hr. PC, every 2 hr. for 12 hr. before and after subcutaneous injection of 3 or 12 mg. of PGF 2a or PGE 2 dissolved in 1 m!. of physiologic saline. The rabbits were autopsied 48 hr. PC and the oviducts were divided and flushed. This experiment was performed to study the effects of different doses of PGF 2a or PGE 2 on oviductal motility and egg transport. One dose of 6 mg. of PGF 2a was administered at 12 hr. PC to five rabbits and at 24 hr. PC to five others. Oviductal motility was monitored every 2 hr. for 12 hr. before and after injection. At 36 hr. PC, autopsy and segmental flushings were carried out. This experiment was performed to study the effect of 6 mg. of PGF 2", injected at different intervals postcoitum, on oviductal motility and egg transport. RESULTS
Oviductal Motility. At 24 hr. PC, oviductal motility was monitored in eight untreated rabbits every 2 hr. The periods of recording per rabbit varied between 60 and 120 min. Oviductal motility was stimulated following the injection of 12 mg. of PGF 2a (Fig. lA). A latent period of 15-20 min. was followed by a gradual increase in motility.
Vol. 24
Two hours following injection, there was a remarkable increase in the amplitude and duration of contractions. The stimulated pattern was recorded at 4, 6, 8, and 10 hr. after injection. Twelve hours after PGF 2a administration, the motility returned to its initial pattern. When one dose of 3 mg. of PGF 2a was injected 24 hr. PC, a stimulated pattern was observed 2-2.5 hr. following the injection, and it lasted for 3-4 hr. The amplitude and duration of contractions were considerably less than those observed following injection of 12 mg. The effectiveness of PGF 2a in stimulating oviductal contractility was most remarkable following the subcutaneous injection of 12 mg.; it was minimal when the dose was 3 mg., and intermediate following 6 mg. The response of the oviduct following the injection of 6 mg. ofPGF 2a at 12 hr. PC was similar to its response when the same dose was injected 24 hr. PC. Oviductal motility was initially inhibited following PGE 2 injection (Fig. IE). When one dose of 12 mg. of tlGE 2 was administered 24 hr. PC, a latent period of 10-15 min. was followed by a gradual decrease in the motility and a remarkable decrease in the amplitude of contraction for 3-4 hr. The motility returned to its initial level 4.5-5 hr. after the injection, which was followed by secondary stimulation for 2-3 hr. The motility finally returned to the initial level 8-10 hr. after injection. When one dose of 3 mg. of PGE 2 was injected 24 hr. PC, an inhibited pattern was observed following a latent period of 20-30 min. This inhibition was observed for 1-2 hr. and a compensatory stimulation was noted for 30-60 min. Egg Transport. In untreated rabbits, 89% of eggs were recovered from the third segment of the oviduct and no eggs were recovered from the uteri at 48 hr. PC. When one dose of 12 mg. of PGF 2" was injected 24 hr. PC, 63% of eggs were recovered from the fourth segment of the ovi-
.
September 1973
673
IN VIVO OVIDUCTAL MOTILITY
A
B
:_11
Hrs. after inj. 2
4
6
o 25
8
o 25
12
o MINUTES
>-
.>
,.
MINUTES
FIG. 1. Oviductal motility in vivo in rabbits. A, following one dose of 12 mg. of prostaglandin F' a injected subcutaneously 24 hr. postcoitum. Note that the stimulated oviductal motility returned to its initial pattern 12 hr. after injection; B, following one dose of 12 mg. of prostaglandin E. injected subcutaneously 24 hr. post· coitum. Note that oviductal motility was primarily inhibited for 4 hr., secondarily stimulated 8 hr. after the injection, then returned to its initial level 12 hr. after the injection.
ducts 48 hr. PC and 36% from the uteri. When one dose of 3 mg. of PGF 2a was injected, 33 and 62% of eggs were recovered from the third and fourth segments of the oviducts, respectively, and 4% were recov· ered from the uteri. When 6 mg. of PGF 2a were injected 24 hr. PC, 47% of eggs were recovered from the fourth segment of the oviducts 36 hr. PC and 4% from the uteri. However, when PGF 2a was injected 12 hr. PC, 8% of eggs were recovered from the fourth segment of the oviducts and no eggs were recovered from the uteri. When 3 or 12 mg. of PGE 2 were injected 24 hr. PC, a slight disturbance in egg transport was observed, and no eggs were recovered from the uterus at 48 hr. PC. At 48 hr. PC, the percentage of egg recovery in PGF 2a-treated rabbits was less than that
in PGE 2-treated and untreated rabbits. In PGF 2a -treated rabbits, the percentage of eggs recovered 36 hr. PC was higher than the percentage of recovery 48 hr. PC. It is assumed that unrecovered eggs were expelled from the genital tract. At 48 hr. PC, 10 eggs were recovered from the uteri of PGF 2a-treated rabbits; four were unfertilized and six were at the 16- to 32-cell stage. No eggs were recovered from the uteri of PGE 2-treated or untreated rabbits (Fig. 2). DISCUSSION
Functionally, the oviduct is divided into various segments, each of which exhibits an independence evidenced by the asynchronous appearance of outbursts of increased activity in the varied segments. In
674
Vol. 24
AREF ET AL.
FLUSHED EGGS
••••
••••
•• •••• ••••
• •••
•••• ••••
• •• •••• • •••
••••
,..
Control ••••• ••
Minutes
•• •• •••• ••••
Segments
~'= Uterus UTJ 4
3
~"""""" 2
1
FIG. 2. Egg transport and oviductal motility in rabbits as affected by a single dose of 12 mg. of prostaglandin F 2. (PGF ..) or prostaglandin E2 (PGEJ subcutaneously injected 24 hr. postcoitum. Oviductal motility was recorded in vivo in one oviduct at 2 and 8 hr. following prostaglandin injection. Eggs were recovered from the contralateral side by segmental flushing. Note that PGF •• was effective only in hastening egg transport. Oviductal motility was stimulated in response to PGF 2a injection. PGE. injection caused an initial inhibition followed by secondary stimulation 8 hr. after injection. UTJ, utero-tubal junction.
the rabbit, these outbursts were characterized by sets of intense muscular contractions and a gradual increase in the intraluminal pressure, followed by a decrease in the intensity of the contractions and a lowering of intraluminal pressure. This pattern may suggest the overcoming of a distal antagonism, which, when yielded, resulted in the lowering of the intraluminal
tension and expulsion of the contents further to the distal segment. The mechanism of retention of ova at the ampullary isthmic junction is of considerable importance in timing egg transport through the oviduct. Strong oviductal contractions could prematurely expel the eggs to the uterus and terminate pregnancy. Prostaglandins exert remarkable effects
September 1973
•
>
IN VIVO OVIDUCTAL MOTILITY
675
on the contractility of the oviduct in vivo. taneously increased the oviductal motility In rabbits, local instillation of 0.4 mg. of for 8-12 hr. and effectively hastened egg PGE 1 in the oviduct induced an immediate transport when injected 24 hr. PC. The paralyzing effect for 3-5 min. The contrac- effectiveness of PGF 2a in stimulating ovitions returned gradually to the initial level ductal motility was independent of the within 5-20 min. The contractions of the reproductive phase. PGF 2a stimulated ovisame oviduct increased 5-7 hr. following ductal motility when injected 12 or 24 hr. the injection of 2.4 mg. and reached a PC. However, its effectiveness in hastening maximal level after 9-14 hr.lO Spilman egg transport was remarkable when inand Harper 5 reported a large decrease in jected 24 hr. PC and was partial when the basic tone and a decrease in the frequency same dose was injected 12 hr. PC. lt is possible that the effectiveness of for 7 min. following intravenous administration of PGE I or PGE 2 • PGF I at doses of PGF 2a in hastening egg transport could 50, 100, or 200 p,g. intravenously evoked only be elicited during a specific phase of a sustained increase in the tone which the reproductive cycle. The intensity ofthe lasted 5.5 min. The subcutaneous injection contractile response of the oviduct followof PGE 2 (0.5-1.5 mg.) suppressed ovi- ing prostaglandin injection, however, deductal activity for. 20-40 min., whereas pends upon the dose administered. The PGF 2a (7.5 mg.) increased the frequency presence of 16- to 32-cell stage morulae in and amplitude of contractions for 1-1.5 hr. the uteri of PGF 2a-treated rabbits 48 hr. A stimulatory response was observed in PC provided evidence that egg transport women following the injection of 100 ILg. through the oviducts was hastened. of PGF 2a intravenously. Injection of 100 Further studies are needed to determine p,g. of PGE 2 , however, was followed by the fate of these rapidly transported eggs. Interference with implantation and/or coninhibition. 2 In the rabbit, 5 mg. of PGE 1 and PGF 2a ception will determine the future use of subcutaneously hastened the transport of prostaglandin F 2a as a possible postcoital the eggs to the uterus by approximately 40 contraceptive. hr. II Following subcutaneous injection of PGF 2a (5 mg./kg.), no eggs were recovered SUMMARY from the oviduct and few eggs were recovered from the uterus. 12 Following the injecProstaglandins F 2" and E2 (3, 6, and 12 tion of PGE 1 (5 mg./kg.) subcutaneously, mg.) were subcutaneously administered egg transport was partially hastened, but to rabbits at 12 and 24 hr. PC. In vivo PGE 2 was ineffective in altering the rate oviductal motility was monitored in one of egg transport in the rabbit oviduct. oviduct and egg transport was studied on In this study, subcutaneous injection of the contralateral side. PGF 2a effectively 12 mg. of PGE 2 inhibited the contractility hastened egg transport when injected 24 for 4-5 hr. Six hours after its injection, the hr. PC and its effect was less remarkable motility returned to the initial pattern, and when injected 12 hr. PC. The effectiveness a secondary stimulation was gradually es- of PGF 2<> in stimulating oviductal motility tablished. The ineffectiveness of PGE 2 in and in hastening egg transport was higher delaying egg transport through the oviduct when the dose injected at 24 hr. PC was could be attributed to its short duration of increased from 3 to 12 mg. The subcutaneaction and to the compensatory secondary ous administration of PGE 2 at 24 hr. PC stimulation 8 hr. following its injection. On was ineffective in altering egg transport, the other hand, 12 mg. of PGF 2a subcu- and its primary inhibitory effects on ovi-
676
AREF ET AL.
ductal motility were compensated by delayed stimulation. Acknowledgments. The authors gratefully acknowledge Dr. Kazuo Sano of ONO Pharmaceutical Co., Osaka, Japan, for providing the prostaglandins; and Ayerst Laboratories, Inc., New York, for providing human chorionic gonadotropins.
6.
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