Tubal and uterine motility in vivo in the rhesus monkey

EUROP.

J. OBSTET.

GYNEC.

REPROD.

BIOL.,

6/3,93-101.

EXCERPTA

MEDICA

Tubal and uterine motility in vivo in the rhesus monkey* A. Neri **, S.L. Marcus *** Department

and F. Fuchs

of Obstetrics and Gynecology,

Cornell University Medical College, New York, N. Y., U.S.A.

NERI, A., MARCUS, S.L. and FUCHS, F. (1976): Tubal and uterine motility in vivo in the rhesus monkey. Europ. J. Obstet. Gynec. reprod. Biol., 613, 93 -101. Previous data indicate that there are definite qualitative and quantitative patterns of tubal activity during the various phases of the menstrual cycle. In the present investigation, the simultaneous activity of the uterus and Fallopian tube was recorded in vivo in mature rhesus monkeys throughout the menstrual cycle. The observations indicate that there are characteristic patterns of both tubal and uterine activity, depending on the various phases of the menstrual cycle. The simultaneous recordings of tubal and uterine activity show that the tubal and uterine contractions are not synchronous or even have a similar pattern. The presence of a transmetrial catheter for recording of uterine activity seems to modify +he patterns of tubal activity, particularly during the ovulatory phase. It seems possible that the transmetrial catheter has a similar effect as an intrauterine contraceptive device in this species. menstrual

cycle; patterns

of activity

of tubes and uterus

In the primate, as well as in other animals, various processes of critical importance in the reproductive cycle take place within the oviduct. Among these processes are the transport of ova and spermatozoa, the fertilization of the ovum, and the cleavage of the fertilized ovum. The precise role of tubal contractions in these processes remains to be elucidated. It is known, however, that a delicate mechanism is involved in the ovum transport and that significant interference with the synchronization between ovular and endometrial development can result in failure of implantation to occur. It is reasonable to suppose that alterations in the normal pattern of tubal motility can alter the ovum pick-up mechanism, the ovum transport pro-

cess, or the entrance of the blastocyst into the uterus and therefore adversely affect fertility. Conversely, it also is possible that contraception can be achieved by deliberately altering the normal pattern of tubal motility. In a previous publication (Neri, Marcus and Fuchs, 1972), the spontaneous activity of the oviduct was evaluated in vivo in mature rhesus monkeys using an open-end catheter technique. The data indicated definite qualitative and quantitative patterns of tuba1 motility during the various phases of the menstrual cycle. The purposes of the present study were to simultaneously record tubal and uterine contractions in vivo throughout the menstrual cycle and to compare the patterns of activity in the tube and uterus.

* This study was supported by Grant No. 67455 from The Ford Foundation. ** Ford Foundation Fellow, 1968-1969: Present address: Beilinson Hospital, Tel Aviv University Medical School, Tel Aviv, Israel. *** Deceased, July 15,1975.

Materials

and methods

Six rhesus monkeys, weighing 4-6 kg, comprised the material for study. The animals were mature fe93

A. Neri et al.: Tubal and uterine motility in vivo

94

mm Hg aok

mm Hg

5

15

IO

20

25

mmH 40 30 20 IO

Y

Fig. 1. Tubal activity in a monkey with an openend catheter in the Fallopian tube only (top tracing) and simultaneous tubal and uterine activity in another monkey with one catheter in the tube (middle tracing) and one inserted transmetrially into the uterus (bottom tracing). Both animals were studied on day 2 of the menstrual cycle.

males with regular menstrual cycles; they were observed through 4 cycles prior to the study. The menstrual cycles were characterized by vaginal cytology every other day using the criteria of DeAllende, Shorr and Hartman (1945) and by weekly plasma progesterone determinations using a competitive proteinbinding method. A laparotomy was perfomed under sodium pentobarbital * anesthesia for the insertion of openend catheters into one of the oviducts and the uterus. The fenestrated tip of a Teflon ** tube (#6439 thin wall, *Diabutal, Diamond Laboratories, Inc., Des Moines, Iowa. ** Becton-Dickinson and Company, Rutherford, New Jersey.

ID 0.034” X OD 0.058”) was inserted into the ampullary portion of the oviduct through the fimbriated end, which was lightly occluded with a ##OOOOO silk suture. The external end of the Teflon tube was delivered through the abdominal wall via a small paramedian incision and was secured to the abdominal fascia by a single ##OOOsilk suture. Another Teflon tube was inserted into the uterine cavity through a small incision in the fundus. The hole was closed around the Teflon tube with a #BOO00 silk suture. The tube was led through the abdominal wall at the lower end of the incision and connected to a similar transducer. The external ends of the tubes, which were filled with heparmized

A. Neri et al.: Tubal and uterine motility in vivo

95

mm Hg 20 15 IO 5

i,il I

01

5

I

IO

I

15

I

I

20

25 Min.

mm Hg 20 I5 IO

5

II 5

IO

I5

20

25 Min.

Fig. 2. Recordings from 2 monkeys on day 5 of the cycle. Top tracing: only tube catheterized; simultaneous recordings from tube and uterus.

physiological saline solution, were connected to pressure transducers (Model 267 BC, Sanborn Company) which transmitted the impulses to an amplifierrecorder (Model 32 1 Dual Channel Carrier AmplifierRecorder, Hewlett-Packard). By intermittent flushing the patency of the system was ascertained. This method permitted quantitative recording the intratubal pressure changes by a simple transmission through a fluid column to an electronic pressure transducer. The advantage of this open-end technique over a balloon method have been detailed by Hendricks (1964). Observations of human uterine motility utilizing the openend technique have been reported by Hendricks (1964) Cibils (1967), Bengtsson

middle and bottom tracings:

(1968) and others. A similar open-end technique for recording uterine motility in the rhesus monkey has been reported by Martin and Eckstein (1966) Harry and Pickles (1968) and Harbert, Cornell, Was and Thorton (1971). For recording of tubal motility, similar techniques have been utilized by Gomez-Rogers, Ibarra Polo, Garcia-Huidobro, Moran, Guiloff and Millan (1967), Maia and Coutinho (1970), SicaBlanco, Cibils, Remedio, Rozada and Gil (1971), and Neri et al. (1972). The initial recordings in each animal were performed on the day of laparotomy and insertion of the Teflon tubes. The external ends of the tubes were left in place on the abdominal wall and covered with a

A. Neri et al.: Tubal and uterine motility in vivo

96 mm Hg

0

I

5

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I

20

25

I

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IO

I!i

Min. mm Hg

0'

I

5

I

IO

I

I

15

20

I

I

/ 25 Min.

’

Fig. 3. Recordings from 2 monkeys on day 12 of the cycle. Top tracing: only tube catheterized; simultaneous recordings from tube and uterus.

sterile dressing for subsequent recordings. The tubal and uterine activity was recorded from once daily to twice weekly throughout the various phases of the menstrual cycle, the duration of each recording session ranging from 4 to 8 h. A total of 50 recordings were made on the 6 animals. Sernylan * (phencyclidine hydrochloride) was given intramuscularly to each animal prior to removal from its cage. During the actual recordings, a microinfusion of sodium pen* Semylan, Parke, Davis & Company, Detroit, Michigan.

middle and bottom tracings:

tobarbital in 5% dextrose in water was given in the minimal dosage required to maintain the animal in a fairly quiescent state. Since it is impossible to record without some anesthesia, the effect of this minimal dose on the contractions cannot be ascertained. A group of 10 monkeys, in which no catheters were placed in the uterus and tubal motility only was recorded, served as controls. The observation in this group formed the basis for our previous report (Neri et al., 1972). Figures l-6 illustrate typical recordings of tubal

A. Neri et al.: Tubal and uterine motility in vivo

01 mm

5I

I

97

1

IO

15

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20

25 Min.

Hg

20 IS-

‘111 0

I

5I

IO

15

20

25

mm’tig 20 L

0'

I

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I

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5

IO

I5

20

25 Min.

Fig. 4. Recordings from 2 monkeys on day 13 of the cycle. Top tracing: only tube catheterized. top and middle.

activity from the previous study (top tracings), compared to simultaneous recordings of uterus and tubal activity (middle and bottom tracings, respectively). As described,,the recordings of the tubal activity only revealed a pattern consisting of small contractions and outburst of contractions of greater amplitude at fairly regular intervals. The frequency, amplitude and duration of the outbursts of greater activity varied according to the phase of the menstrual cycle. Middle and bottom tracings in Figures l-6 indicate that tubal and uterine contractions are independent of each other and are usually asynchronous. The general patterns of activity of the uterus and tube differ considerably. Uterine contractions are general-

Note the difference between the

ly of greater amplitude and frequency, with the greatest activity in the uterus being observed during menstruation. Comparison of recordings of the tube alone and of the tube and uterus simultaneously indicates that the presence of a transmetrical catheter can alter the pattern of tubal activity. This alteration is particularly evident during the ovulatory phase when there is a significant decrease in amplitude and an increase in frequency of contractions (Figs. 4 and 5). In the other phases of the cycle, however, the general patterns of tubal activity were maintained. Table I summarizes the mean amplitude and mean frequency of the group with simultaneous tubal and

A. Neri et a%: Tubal and uterine motility in vivo

I

I

I

1

1

5

IO

I5

20

25 Min.

mm Hg

20

0

I

5

I IO

I

,

I

I5

20

25 Min.

5

IO

I5

20

25 Min.

Fig. 5. Recordings from 2 monkeys on day 14 of the menstrual cycle. Top tracing: only tube catheterized. scale of pressure between the top and middle tracings.

uterine activity and of the control group with tubal activity alone according to the phase of the menstrual cycle. The trends indicate that the contractions of the greatest amplitude (45 mm Hg) and the largest mean amplitude (25 mm Hg) in the tube alone were observed during the ovulatory phase. Although the late luteal phase revealed a return of the higher-amplitude bursts of contractions (Fig. 6, top tracing), this observation is not reflected in the mean amplitude value since the range was considerable. Regarding the frequency of contractions when recordings of the tube alone were made, Table I reveals that the frequency

Note the different

was greatest in the late luteal, menstrual, and early follicular phases with a progressive decrease in frequency as the ovulatory phase was approached.

This study has confirmed the feasibility of using openend catheters for direct, simultaneous recordings of tubal and uterine contractility in the rhesus monkey, and of repeating the recording during various phases of the menstrual cycle.

A. Neri et al,: Tubal and uterine motility in vivo

99

I

I

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IO

15

20

25 Mln

o-

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10

15

1

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25

20 Min.

mm Hg

01

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20 Min.

Fig. 6. Recordings from 2 monkeys on day 25 of the cycle. Top tracing: only tube catheterized. pressure between the top and middle tracings.

Uterine and tubal activity appears to be qualitatively and quantitatively different, as well as asynchronous. The same was observed in women by Coutinho and Maia (1970). In unpublished studies of ours, in which both tubes were recorded simultaneously, lack of synchrony between the two tubes was noted, and this, too, has been observed in human in vivo studies (Sica-Blanco, Roxada, Remedio, Hendricks and Alvarez, 1970). Although distinct patterns of tubal and uterine motility were found during the recordings, it should be pointed out that occasionally spontaneous alterations of these patterns occurred. However, the pattern which appeared to be characteristic for the par-

Note the different scale of

titular phase of the cycle quickly reappeared and was usually maintained for long periods of recording in each animal. On the basis of the data from this study, it is impossible to draw any conclusions about the relationship between tubal contractions and the transport of spermatozoa and ova. Maia and Coutinho (1970) and Sica-Blanc0 et al. (1971) have recorded simultaneously the pressures at 2 or 3 points of the human tube in vivo and observed both peristalsis and antiperistalsis during the follicular and luteal phases of the cycle. Since our studies were carried out, a number of studies of the effects of sympathomimetic drugs on

A. Neri et al.: Tubal and uterine motility in vivo

100 TABLE I

Recording of the tubal activity in 10 rhesus monkeys and of simultaneous activity of the Fallopian tube and uterus in 6 monkeys during the various phases of the menstrual cycle

Phase of cycle

Mean amplitude * (mm Hg) Tube

Tube

Mean frequency* Uterus

Tube

Simultaneous activity recordings Menstruation (day l-4)

(per 20 min) Tube

Uterus

Simultaneous activity recordings

9 (8-10)

8 (6-17)

35 (20-43)

63 (60-66)

;:2 -60)

32 (25 -42)

Early follicular (day 5 -8)

11 (9-14)

9 (6-11)

23 (17-36)

66 (64-68)

79 (68-98)

20 (16-60)

Late follicular (day 9-12)

::5 -20)

12 (8-20)

19 (8-30)

39 (25-51)

47 (42-53)

33 (28-43)

Ovulatory (day 13-16)

25 (15-45)

;3-6)

::5 -23)

:380-50)

72 (70-74)

37 (18-48)

Farly luteal (day 17 -22)

13 (8-18)

10 (6-18)

12 (5-18)

49 (32-72)

74 (56-96)

38 (26-54)

Late luteal (day 23-31)

10 (8-21)

19 (12-25)

16 (8-20)

58 (45 -70)

68 (66-70)

79 (77-82)

* The figures for amplitude and frequency are based upon evaluation of all contractions, bursts of contractions. Figures in parenthesis,represent the range of values.

the human oviduct in vivo have been published (Cibils, Sica-Blanco, Remedio, Rozada and Gil, 1971; Coutinho and Maia, 1970). These studies show that the Fallopian tubes have both alpha- and betaadrenerglc receptors and that the ‘spontaneous’ motility of the tubes can be altered by sympathomimetic compounds. Neri and Marcus (1972) found a biphasic effect of nicotine on the oviduct of the rhesus monkey in the first half of the cycle but only a slight effect in the second half, indicating that the ovarian steroids must have a modulating effect on the response to stimulation, just as is the case with myometrium. The difference between the tubal and uterine contractility is most strikingly illustrated by the response to oxytocin and vasopressin, the human tube being more sensitive to oxytocin, while the uterus is much more sensitive to vasopressin during the menstrual cycle (Coutinho and Maia, 1970). The mechanism by which a transmetrial catheter may alter the pattern of tubal motility should be further investigated. It is interesting that the most marked alterations in tubal motility occurred during

i.e. low amplitude contractions and the

the ovulatory phase of the cycle. One may speculate that the transmetrial catheter could have an effect similar to that of an intrauterine device. In our previous studies in rhesus monkeys in which tubal recordings were obtained with an intrauterine device in the uterus (Neri et al., 1972), similar patterns as in Figures 4B and 5B were noted. However, Coutinho has recorded tubal motility in the human with and without simultaneousuterine recording without noticing any difference in the tubal patterns (personal communication, 1974).

References

Bengtsson, L.P. (1968): The sponge-tipped catheter - a modification of the open end catheter for recording of myometrial activity in vivo. J. Reprod. Fe&Z., 16, 115. Cibils, L.A. (1967): Contractility of the non-pregnant human uterus. Obstet. and Gynec., 30, 441. Cibils, L.A., Sica-Blanco, Y., Remedio, M.R., Rozada, H. and Gil, B.E. (1971): Effect of sympathomimetic drugs upon the human oviduct in vivo. Amer. J. Obstet. Gynec., I IO, 481.

A. Neri et al.: Tubal and uterine motility in vivo

Coutinho, E.M. and Maia, H.S. (1969): Asynchronism between tubal and uterine activity in women. J. Reprod. Fertil., 19, 591.

Coutinho, E.M. and Maia, H. (1970): The influence of the ovarian steroids on the response of the human Fallopian tubes to neurohypophyseal hormones in vivo. Amer. J. Obstet. Cynec.,

108, 194.

Coutinho, E.M., Maia, H. and Adeodato Filho, I. (1970): Response of the human Fallopian tube to adrenergic stimulation. Fertil. and Steril., 21, 590. DeAllende, F.L.C., Shorr, E. and Hartman, C.G. (1945): A comparative study of the vaginal smear cycle in the rhesus monkey and the human. Contrib. Embryol., 31, 326. Garcia-Huidobro, M., Gomez-Rogers, C., Ibarra Polo, A., Guiloff, E., Faundes Latham, A., Quitanilla, R., Avendano, S., Espinosa, J. and Ramirez, R. (1966): II. Reunion Assoc. Latin0 Americana Vina del Mar, Chile. Resumenes,

Invest. Reprod. Humana,

p. 5 3. Gomez-Rogers, C., Ibarra Polo, A. Garcia-Huidobro, M. Moran, A., Guiloff, E. and Millan, C. (1967): Physiology of the human Fallopian tube - in vivo and in vitro studies. In: Proc. 8th Internat. Conf. IPPF, Santiago, Chile, p. 443.

Harbert, G.M., Jr., Cornell, G.W., Wax, S.H. and Thorton, W.N. (1971): Spontaneous uterine activity in non-pregnant primates (Macaca mulatta). Obstet. and Gynec., 37, 487.

101 Harry, J.D. and Pickles, V.R. (1968): A method of recording myometrial contractions in the non-pregnant rhesus monkey in vivo. J. Endocr., 41, 105. Hendricks, C.H. (1964): A new technique for the study of motility of the non-pregnant human uterus. J. Obstet. Cynaec. Brit. Cwlth, 71, 712.

Maia, H.S. and Coutinho, E.M. ((1970): Peristalsis and antiperistalsis of the human Fallopian tube during the menstrual cycle. Biol. Reprod., 2, 305. Martin. C.B. and Eckstein, P. (1966): Transcervical uterine catheterization in rhesus monkeys. Amer. J. Obstet. Gynec., 94,415.

Neri, A. and Marcus, S.L. (1972): Effect of nicotine on the motility of the oviducts in the rhesus monkey: a preliminary report. J. Reprod. Fertit., 31, 9 1. Neri, A., Marcus, S.L. and Fuchs, F. (1972): Motility of the oviduct in the rhesus monkey. Obstet. and Gynec., 39, 205.

Sica-Blanco, Y., Cibils, L.A.. Remedio, M.R., Rozada, H. and Gil, B.E. (1975): Isthmic and ampullar contractility of the human oviduct in vivo. Amer. J. Obstet. Gynec., 111,91.

Sica-Blanco, Y., Rozada, H., Remedio, M.R., Hendricks, C.H. and Alvarez, H. (1970): Human tubal motility in vivo. .4mer. J. Obstet. Gynec., 106, 79.