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Myoelectrical activity in the human oviduct with tubal pregnancy
Myoelectrical activity in the human oviduct with tubal pregnancy M. O. Pulkkinen and A. Talo*
Turku, Finland Myoelectrical activity and progesterone (P) and 1713-estradiol (E2 ) concentrations were measured in 12 human oviducts with tubal pregnancy. Spikes were frequently superimposed on a single, smooth , slow wave. The region above a large conceptus (P dominance) was inactive in eight of 10 oviducts. The myoelectrical activity spread toward these conceptuses from both sides , apparently holding the conceptus in place. In three cases with small placentas , the spread of weak activity tended to push the conceptus out of the oviduct. A steep decline of P and E2 levels distally in both directions from the conceptus was coincident with frequency of peaks. (AM . J . OBSTET. GVNECOL. 148:151, 1984.)
A good method for reliably characteriz ing tubal motility with a minimal risk of ar tifacts is to measure th e electrical activity with spec ial suction electrodes. This electrical activity preced es the mech an ical activity and also reflects its force . It beca me possible only re cently to make a de tailed analysis of the initi ati on and spread of myoelectrical activity in norm al ovidu cts during th e menstrual cycle.' Myoele ctrical activity after menopause resembles th at re corded during the proliferative phase of th e menstrual cycle (estr oge n dominance)." The active amp ulla but in active isthmu s described at menopause could form a fu nctional basis for the high incidence of extrauterine p re gnancies d u r ing the premenopause." We repo rt here the electr ical activity in ovid uc ts with tubal pregnan cy. The stu dy had three aims : (l ) to find a theory as to why the conc eptuses in th ese cases are not aborted into th e abdominal cavity; (2) to ana lyze the properties of myoelectr ical activity when th e mu scul ature can be expected to be under progesterone (P) dominan ce (at the site of extrauterine pregnancy), and (3) to find out whether the steroid gr adients rather than their absolute levels could influence tubal acti vity in a model where a steep gradient exists in the steroid hormone levels. Material and methods
Twelve ovid ucts with am pullar pregn an cy wer e studied . The patients' ages varie d bet ween 21 and 32 years (28 ± 1 yea rs , mean ± SEM ). The conceptuses varied
in size fr om 1 to 3 ern. In two cases the ampullar y walls were ruptured and the placentas spread to the serosal sid es of th e ovid uc ts. After salpingecto my, th e oviducts were pu t in to cold, oxygenated ph ysiologic saline solution , and th e ligaments were dissected off as a sheet, beginnin g fro m the undilated areas, to ex pose the circular mu scle layers . This was a difficult task in the r egion above the co nce p tus since excessive dilatation had flatt en ed the muscle layers, bringing the m into intimate contact with the ligam ents. Myoelectr ical activity was recorded in a tissue bath at 37° ± 0.5 ° C, with the simultaneou s use of six suc tion electrodes, as described earlier. I Recordings were made on a Gr ass 7P pol ygrap h with o ne DC and five AC preampli fiers. Rin ger's solution was oxyg enated and cha nge d co ntinuo usly. In the subse que nt recordings two of th e locati on s were th e same. After recordin g, th e ovidu cts were moved int o Petri di shes, fixed to the bottoms o f th e di shes , and opened longitudinally. The concep tus was rem oved for pathologic ex amination . T he region abo ve the conceptus was cut into two identical halves. In ad d ition , one or two segments were cut in the ampulla and in the isthmu s. Excessive fluid was d ried with tissue paper , and the seg me n ts were fr ozen for determination of P and 17,B-estr ad iol (E2 ) . P and E2 wer e twice extr acted from the hom ogeni zed tissue with petroleum ether and chr oma tog ra phed with Sep ha d ex LH -20 for radioimmunoassay.' The in tra -assay and in teras say coefficient of varia tion was less th an 10%. Results
From the Department of Obstetrics and Gynecology and the Laboratory of An imal Physiology, Department ofB iology, Univer sity of Turku. Received for publication M arch 1, 1983 . R evised September 2, 1983. Accepted September 14, 1983 . Reprint requests: Dr. M. O. Pulkkinen, N aistenklinikka, Ki inamsl1)71katu 8, SF-2052 0 Turku 52, Finland . . *Research Fellow, S uomen Akatemia .
Waveforms. Waveforms were recorded in the region above th e concep tu s, o n both sides of th e conceptu s, in the ampulla, a nd in the isth mus. A sing le, smo oth, slow wave lastin g 2 to 3 seconds was re corded in all re gion s. A spik e co m po nent was com mo n and pronounced (Fig. 1). In the r egion ab ove th e concep tus th e act ivity usually consis ted of irregul ar spikes. In th e isthmus lon g 151
152 Pulkkinen and Tala
January 15. 1984 Am. J. Obstet. Gynecol.
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Fig. 1. Panels A (upper) to D: Waveforms above the conceptus. in the ampulla, and in the isthmus. Note the frequent spike components. Time axis: seconds. Voltage calibrations: 250 f.J. V inA, C, andD and 50 f.J..V inB.
spikes with a fast rate of rise (Fig. I, panel D, second recording) were more common than short spikes (Fig. I, panel D, third recording). Slow waves of about 10 seconds' duration were recorded both in the ampulla and in the isthmus (Fig. I, panels B, C, and D, last recordings). Series of small spikes were sometimes superimposed in the ampulla (panels A ,B, and C) but not in the isthmus. A long-lasting slow wave in the isthmus was recorded in the inner longitudinal muscle layer protruding at the severed end of the isthmus. Pacemakers and direction of spread. The region just above the conceptus was inactive in eight of 10 oviducts with a large conceptus. Myoelectrical activity spread toward the conceptus from both ends (Fig. 2). Rebound activity initiating in the isthmus (pacemaker under electrode site 14) spread toward the uterus. The region .above a small conceptus was active (two oviducts) and had pacemakers. Frequency. A high-frequency area was near the conceptus on the uterine side in all oviducts studied. Fig. 3 illustrates two extreme examples of the variation in frequency of the myoelectrical activity along the oviduct. The tissue levels of P and £2 were approxi-
mately similar. The difference was in the size of the placentas, even when both conceptuses were large. In the oviduct shown in Fig. 3, A the placenta was large, but in that shown in Fig. 3, B it was small. The oviducts differed as to the level of activity in the region above the conceptuses. In the oviduct with a large placenta (Fig. 3, A) this region was inactive, but in the oviduct with a small placenta (Fig. 3, B) activity initiated in the region above the conceptus, where the diameter of the oviduct declined toward the uterus. However, it was not known whether the recording was made on the same side or on the opposite side of the oviduct from the location of the placenta. The activity spread in both directions through the whole of the region above the conceptus with a small placenta. P and E2 concentrations along the oviduct with tubal pregnancy. In all cases the highest steroid concentrations were found in the region above the conceptus (Table I). Concentrations declined distally from the region of the conceptus in both directions (Fig. 3). The lowest P and £2 concentrations were measured in the oviduct with a conceptus with a short diameter and a small placenta.
Myoelectrical activity with tubal pregnancy
Volume 148 Number 2
153
o o o o o o o o o o o o o o
o o o o Fig. 2. A composite of four original recordin gs covering the length of the oviduct with tubal pregnancy. Subsequent recording s are separated by continuous lines. 'DIe recording sequence is from top to bottom. Pacemaker activity is indicated by small circles at recording points 2, 3, 5, 11,12, and 14. Arrow indicates direction of spread. For main direction, see arrows between the oviduct diagram and the recordin gs.
Comment
The present findings sho w that in most isolated oviducts th e spread of acti vity is such that it does not co ntribute to the abortion of th e conceptus into the abdominal cavity. T he activity has pe aks of fr equency on both sid es ofth e co nce ptu s a nd spread s toward the co nce ptus from both directions. This effectivel y ca ncels th e effects of co n tr actions o n the opposite sid e . In two cases with small placentas, in which the sp read of activity tended to push the conceptus out of the oviduct, the activity was weak and appa rently could not accom plish the abortion. The tissu e levels of P a nd E2 were in acco rd with those of previous find ings: During estrogen dominance the waveform is a smooth, single , slow wave, lasting a few seconds. When the P level is high, th ere a re often spikes on the tops of the slow waves. In the oviduct with tubal pregnancy the spike component was more pronounced th an during the menstrual cycle or the post-
menopausal period. I . Z I t a ppea rs th a t when the pla ce n ta is large a nd produces a large amount of P th e oviductal activity alm ost co m pletely disappears. There may, however, be facto rs other than P, £2, or stretch that d eterrnine the level of activity. It is not likel y th at the lack of activity is caused by the immediate effects of stretch , since in two of t he cases in wh ich the conceptus was removed activity was present in one ovid uct but not in the other. There was a steep decline of P and E 2 levels distally in both directions from th e conceptus. The peak frequency was recorded either at the site above the conceptus or where the di amet er declined . This su gge sts that there may be a cr itical PlE 2 ratio whi ch induced a high level of activity in the human oviduct. In the rabbit oviduct not only the absolute hormone levels but also the tim e course is important for regulation of the activity level. £ 2 withdrawal greatly enhances the transport velo city of the ova in the rabbit ampulla." The
154 Pulkkinen and Talo Am.
4 1
13 3
410 21
97 11
31 2
18 3
10
4
20
9
13
7
PROGESTERONE (PI ESTRADIOL- 17fl (E21
Table I. P and E 2 levels (mean ± SEM) in the human oviduct with tubal pregnancy
RATIO p/E2
I P (pg/mg) Ampulla (n = 7) Conceptus site (n = 10) Isthmus (n = 9)
50
100°/0
- - - _ . _ - _.. _ -
"c3 'E 2 u,
-
30 11
85 11
350 29
46 17
23 12
16 4
PROGESTERONE (PI ESTRADIOL-17" (E21
3
8
2
3
2
4
RATIO P/E2
0
4
27 ± 13 263 ± 115 29 ± 10
£2 (pg/mg)
4±1 17 ± 4 3 ± I
1][ ratio
7
16 10
production may have been decreasing because the conceptus appeared to be regressing rather than developing. The above findings support Csapo's" "local P-block" concept, as we stressed earlier.' We thank Ms. Sinikka Hillgren, Ms. Marjo Koskela, and Ms. Siro Rauti for technical assistance.
J
REFERENCES
1
0
January 15, 1984 Gynecol.
J. Obstet.
50
100 °10
Fig, 3. Two extreme examples of the variation in frequency of myoelectrical activity along the pregnant oviduct. A (upper): Large placenta; B: small placenta (indicated by circle). Oviduct area above the conceptus is inactive and peak frequency is on both sides of the conceptus in A; area above the conceptus side is active (with peak frequency) in B. P and E2 levels are given as picograms per milligram. direction of change of the hormonal levels in the oviduct prior to salpingectomy may have affected the results of the present study. In three oviducts with activity in the region above the conceptus, hormone
1. Talo, A., and Pulkkinen, M. 0.: Electrical activity in the human oviduct during the menstrual cycle, AM.J. OBSTET. GYNECOL. 142: 135, 1982. 2. Pulkkinen, M. 0., and Talo, A.: Electrical activity in the postmenopausal oviduct, Maturitas. In press. 3. Niles, J. H., and Clark, J. F. J.: Pathogenesis of tubal pregnancy, AM. J. OBSTET. GYNECOL. 105:1230,1969. 4. deVilla, G. 0., Roberts, K., Wiest, W. G., Mikhail, G., and Flickinger, G.: A specific radioimmunoassay of plasma progesterone, J. Clin. Endocrino!' Metab. 35:458, 1972. 5. Boling, J. L., and Blandau, R. J.: The role of estrogens in egg transport through the ampullae of oviducts of castrate rabbits, Ferti!. Steri!. 22:544, 1971. 6. Csapo, A. I.: Progesterone "block," Am. J. Anat. 98:273, 1956. 7. Pulkkinen, M. 0.: Control of labor by local placental progesterone, in International Congress Series No. 512, Amsterdam, 1980, Excerpta Medica, p. 336.
Turku, Finland Myoelectrical activity and progesterone (P) and 1713-estradiol (E2 ) concentrations were measured in 12 human oviducts with tubal pregnancy. Spikes were frequently superimposed on a single, smooth , slow wave. The region above a large conceptus (P dominance) was inactive in eight of 10 oviducts. The myoelectrical activity spread toward these conceptuses from both sides , apparently holding the conceptus in place. In three cases with small placentas , the spread of weak activity tended to push the conceptus out of the oviduct. A steep decline of P and E2 levels distally in both directions from the conceptus was coincident with frequency of peaks. (AM . J . OBSTET. GVNECOL. 148:151, 1984.)
A good method for reliably characteriz ing tubal motility with a minimal risk of ar tifacts is to measure th e electrical activity with spec ial suction electrodes. This electrical activity preced es the mech an ical activity and also reflects its force . It beca me possible only re cently to make a de tailed analysis of the initi ati on and spread of myoelectrical activity in norm al ovidu cts during th e menstrual cycle.' Myoele ctrical activity after menopause resembles th at re corded during the proliferative phase of th e menstrual cycle (estr oge n dominance)." The active amp ulla but in active isthmu s described at menopause could form a fu nctional basis for the high incidence of extrauterine p re gnancies d u r ing the premenopause." We repo rt here the electr ical activity in ovid uc ts with tubal pregnan cy. The stu dy had three aims : (l ) to find a theory as to why the conc eptuses in th ese cases are not aborted into th e abdominal cavity; (2) to ana lyze the properties of myoelectr ical activity when th e mu scul ature can be expected to be under progesterone (P) dominan ce (at the site of extrauterine pregnancy), and (3) to find out whether the steroid gr adients rather than their absolute levels could influence tubal acti vity in a model where a steep gradient exists in the steroid hormone levels. Material and methods
Twelve ovid ucts with am pullar pregn an cy wer e studied . The patients' ages varie d bet ween 21 and 32 years (28 ± 1 yea rs , mean ± SEM ). The conceptuses varied
in size fr om 1 to 3 ern. In two cases the ampullar y walls were ruptured and the placentas spread to the serosal sid es of th e ovid uc ts. After salpingecto my, th e oviducts were pu t in to cold, oxygenated ph ysiologic saline solution , and th e ligaments were dissected off as a sheet, beginnin g fro m the undilated areas, to ex pose the circular mu scle layers . This was a difficult task in the r egion above the co nce p tus since excessive dilatation had flatt en ed the muscle layers, bringing the m into intimate contact with the ligam ents. Myoelectr ical activity was recorded in a tissue bath at 37° ± 0.5 ° C, with the simultaneou s use of six suc tion electrodes, as described earlier. I Recordings were made on a Gr ass 7P pol ygrap h with o ne DC and five AC preampli fiers. Rin ger's solution was oxyg enated and cha nge d co ntinuo usly. In the subse que nt recordings two of th e locati on s were th e same. After recordin g, th e ovidu cts were moved int o Petri di shes, fixed to the bottoms o f th e di shes , and opened longitudinally. The concep tus was rem oved for pathologic ex amination . T he region abo ve the conceptus was cut into two identical halves. In ad d ition , one or two segments were cut in the ampulla and in the isthmu s. Excessive fluid was d ried with tissue paper , and the seg me n ts were fr ozen for determination of P and 17,B-estr ad iol (E2 ) . P and E2 wer e twice extr acted from the hom ogeni zed tissue with petroleum ether and chr oma tog ra phed with Sep ha d ex LH -20 for radioimmunoassay.' The in tra -assay and in teras say coefficient of varia tion was less th an 10%. Results
From the Department of Obstetrics and Gynecology and the Laboratory of An imal Physiology, Department ofB iology, Univer sity of Turku. Received for publication M arch 1, 1983 . R evised September 2, 1983. Accepted September 14, 1983 . Reprint requests: Dr. M. O. Pulkkinen, N aistenklinikka, Ki inamsl1)71katu 8, SF-2052 0 Turku 52, Finland . . *Research Fellow, S uomen Akatemia .
Waveforms. Waveforms were recorded in the region above th e concep tu s, o n both sides of th e conceptu s, in the ampulla, a nd in the isth mus. A sing le, smo oth, slow wave lastin g 2 to 3 seconds was re corded in all re gion s. A spik e co m po nent was com mo n and pronounced (Fig. 1). In the r egion ab ove th e concep tus th e act ivity usually consis ted of irregul ar spikes. In th e isthmus lon g 151
152 Pulkkinen and Tala
January 15. 1984 Am. J. Obstet. Gynecol.
o
J,
,,,I,,,
"I,!!
I, , , , ! , , "
,
, ,
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, I
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'",,'
, 1 ,,'
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I
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Fig. 1. Panels A (upper) to D: Waveforms above the conceptus. in the ampulla, and in the isthmus. Note the frequent spike components. Time axis: seconds. Voltage calibrations: 250 f.J. V inA, C, andD and 50 f.J..V inB.
spikes with a fast rate of rise (Fig. I, panel D, second recording) were more common than short spikes (Fig. I, panel D, third recording). Slow waves of about 10 seconds' duration were recorded both in the ampulla and in the isthmus (Fig. I, panels B, C, and D, last recordings). Series of small spikes were sometimes superimposed in the ampulla (panels A ,B, and C) but not in the isthmus. A long-lasting slow wave in the isthmus was recorded in the inner longitudinal muscle layer protruding at the severed end of the isthmus. Pacemakers and direction of spread. The region just above the conceptus was inactive in eight of 10 oviducts with a large conceptus. Myoelectrical activity spread toward the conceptus from both ends (Fig. 2). Rebound activity initiating in the isthmus (pacemaker under electrode site 14) spread toward the uterus. The region .above a small conceptus was active (two oviducts) and had pacemakers. Frequency. A high-frequency area was near the conceptus on the uterine side in all oviducts studied. Fig. 3 illustrates two extreme examples of the variation in frequency of the myoelectrical activity along the oviduct. The tissue levels of P and £2 were approxi-
mately similar. The difference was in the size of the placentas, even when both conceptuses were large. In the oviduct shown in Fig. 3, A the placenta was large, but in that shown in Fig. 3, B it was small. The oviducts differed as to the level of activity in the region above the conceptuses. In the oviduct with a large placenta (Fig. 3, A) this region was inactive, but in the oviduct with a small placenta (Fig. 3, B) activity initiated in the region above the conceptus, where the diameter of the oviduct declined toward the uterus. However, it was not known whether the recording was made on the same side or on the opposite side of the oviduct from the location of the placenta. The activity spread in both directions through the whole of the region above the conceptus with a small placenta. P and E2 concentrations along the oviduct with tubal pregnancy. In all cases the highest steroid concentrations were found in the region above the conceptus (Table I). Concentrations declined distally from the region of the conceptus in both directions (Fig. 3). The lowest P and £2 concentrations were measured in the oviduct with a conceptus with a short diameter and a small placenta.
Myoelectrical activity with tubal pregnancy
Volume 148 Number 2
153
o o o o o o o o o o o o o o
o o o o Fig. 2. A composite of four original recordin gs covering the length of the oviduct with tubal pregnancy. Subsequent recording s are separated by continuous lines. 'DIe recording sequence is from top to bottom. Pacemaker activity is indicated by small circles at recording points 2, 3, 5, 11,12, and 14. Arrow indicates direction of spread. For main direction, see arrows between the oviduct diagram and the recordin gs.
Comment
The present findings sho w that in most isolated oviducts th e spread of acti vity is such that it does not co ntribute to the abortion of th e conceptus into the abdominal cavity. T he activity has pe aks of fr equency on both sid es ofth e co nce ptu s a nd spread s toward the co nce ptus from both directions. This effectivel y ca ncels th e effects of co n tr actions o n the opposite sid e . In two cases with small placentas, in which the sp read of activity tended to push the conceptus out of the oviduct, the activity was weak and appa rently could not accom plish the abortion. The tissu e levels of P a nd E2 were in acco rd with those of previous find ings: During estrogen dominance the waveform is a smooth, single , slow wave, lasting a few seconds. When the P level is high, th ere a re often spikes on the tops of the slow waves. In the oviduct with tubal pregnancy the spike component was more pronounced th an during the menstrual cycle or the post-
menopausal period. I . Z I t a ppea rs th a t when the pla ce n ta is large a nd produces a large amount of P th e oviductal activity alm ost co m pletely disappears. There may, however, be facto rs other than P, £2, or stretch that d eterrnine the level of activity. It is not likel y th at the lack of activity is caused by the immediate effects of stretch , since in two of t he cases in wh ich the conceptus was removed activity was present in one ovid uct but not in the other. There was a steep decline of P and E 2 levels distally in both directions from th e conceptus. The peak frequency was recorded either at the site above the conceptus or where the di amet er declined . This su gge sts that there may be a cr itical PlE 2 ratio whi ch induced a high level of activity in the human oviduct. In the rabbit oviduct not only the absolute hormone levels but also the tim e course is important for regulation of the activity level. £ 2 withdrawal greatly enhances the transport velo city of the ova in the rabbit ampulla." The
154 Pulkkinen and Talo Am.
4 1
13 3
410 21
97 11
31 2
18 3
10
4
20
9
13
7
PROGESTERONE (PI ESTRADIOL- 17fl (E21
Table I. P and E 2 levels (mean ± SEM) in the human oviduct with tubal pregnancy
RATIO p/E2
I P (pg/mg) Ampulla (n = 7) Conceptus site (n = 10) Isthmus (n = 9)
50
100°/0
- - - _ . _ - _.. _ -
"c3 'E 2 u,
-
30 11
85 11
350 29
46 17
23 12
16 4
PROGESTERONE (PI ESTRADIOL-17" (E21
3
8
2
3
2
4
RATIO P/E2
0
4
27 ± 13 263 ± 115 29 ± 10
£2 (pg/mg)
4±1 17 ± 4 3 ± I
1][ ratio
7
16 10
production may have been decreasing because the conceptus appeared to be regressing rather than developing. The above findings support Csapo's" "local P-block" concept, as we stressed earlier.' We thank Ms. Sinikka Hillgren, Ms. Marjo Koskela, and Ms. Siro Rauti for technical assistance.
J
REFERENCES
1
0
January 15, 1984 Gynecol.
J. Obstet.
50
100 °10
Fig, 3. Two extreme examples of the variation in frequency of myoelectrical activity along the pregnant oviduct. A (upper): Large placenta; B: small placenta (indicated by circle). Oviduct area above the conceptus is inactive and peak frequency is on both sides of the conceptus in A; area above the conceptus side is active (with peak frequency) in B. P and E2 levels are given as picograms per milligram. direction of change of the hormonal levels in the oviduct prior to salpingectomy may have affected the results of the present study. In three oviducts with activity in the region above the conceptus, hormone
1. Talo, A., and Pulkkinen, M. 0.: Electrical activity in the human oviduct during the menstrual cycle, AM.J. OBSTET. GYNECOL. 142: 135, 1982. 2. Pulkkinen, M. 0., and Talo, A.: Electrical activity in the postmenopausal oviduct, Maturitas. In press. 3. Niles, J. H., and Clark, J. F. J.: Pathogenesis of tubal pregnancy, AM. J. OBSTET. GYNECOL. 105:1230,1969. 4. deVilla, G. 0., Roberts, K., Wiest, W. G., Mikhail, G., and Flickinger, G.: A specific radioimmunoassay of plasma progesterone, J. Clin. Endocrino!' Metab. 35:458, 1972. 5. Boling, J. L., and Blandau, R. J.: The role of estrogens in egg transport through the ampullae of oviducts of castrate rabbits, Ferti!. Steri!. 22:544, 1971. 6. Csapo, A. I.: Progesterone "block," Am. J. Anat. 98:273, 1956. 7. Pulkkinen, M. 0.: Control of labor by local placental progesterone, in International Congress Series No. 512, Amsterdam, 1980, Excerpta Medica, p. 336.