Role of prostaglandins in contractile activity of the ampulla of the rabbit oviduct.

Contractile activity of the ampulla of rabbit oviducts removed 24 h after an ovulating injection was studied in vitro. Spontaneous activity, field-stimulated activity, and response to phenylephrine were studied in normal, reversed, and scraped (endosalpinx removed) sections of tissues in the presence or absence of inhibitors of prostaglandin synthetase (8 or 51 micrograms/ml indomethacin or 10 or 100 micrograms/ml 5,8,11,14-eicosatetraynoic acid (ETA)). The effects of in vivo treatment with 10 mg/kg of indomethacin on the same responses were examined. Scraped tissues produced more prostaglandin E and F (measured by radioimmunoassay) than did normal tissues, and this production was suppressed by 10 micrograms/ml of indomethacin or 100 micrograms/ml of ETA. Production of prostaglandin by normal tissues was not depressed by these compounds in vitro, but was significantly reduced by pretreatment of the animals with indomethacin in vivo. In the absence of the endosalpinx, the myosalpinx exhibited spontaneous activity and responded to field stimulation and phenylephrine. Scraped and reversed tissues, however, showed a faster decline in response to field stimulation than normal tissues, and this was due to the traumatization. By contrast, traumatization increased the sensitivity of the tissue to respond to phenylephrine. Inhibition of prostaglandin synthetase by low doses of indomethacin or ETA prevented desensitization of the tissue to field stimulation, but this desensitization was little affected by the higher doses of indomethacin in vitro or in vivo. ETA did not affect the phenylephrine dose-response curves and nor did 8 micrograms/ml of indomethacin, whereas the high dose was inhibitory. Spontaneous activity was only affected by the in vivo pretreatment with indomethacin, which prevented the decline in activity of scraped tissue with time.

Contraceptive properties of endotoxin in rabbits.

Endotoxin derived from Salmonella enteritidis-Boivin at a dose of 20 micrograms/kg intravenously interfered with follicular rupture normally induced by human chorionic gonadotropin (hCG) in rabbits. This action was greatest when the endotoxin was given 5 to 6 hours after the administration of hCG. The failure of follicular rupture resulted in entrapment of ova. Endotoxin (5 micrograms/kg) given intravenously to rabbits on day 4 of pregnancy resulted in failure of implantation. Indomethacin (2 micrograms/kg) given intramuscularly concomitantly was unable to reverse this action. Endotoxin (5 micrograms/kg) given intravenously to rabbits on day 8 of pregnancy had an immediate lethal action on embryonic development, and this effect was inhibited by concomitant indomethacin treatment. Nevertheless, most fetuses died after the indomethacin treatment. Whether this was due to a direct toxic action of indomethacin or to a secondary action of endotoxin not blocked by indomethacin is not clear. Endotoxin did not exert its antifertility actions through a luteolytic mechanism.

Effects of gonadotropins on follicular development, ovulation, and atresia in the mature guinea pig.

The induction of follicular growth, ovulation, and atresia by heterologous gonadotropic preparations was studied late in the reproductive cycle of the adult female guinea pig. Human chorionic gonadotropin (HCG) administration (10 IU) 12 days following the first signs of opening of the vaginal membrane was found to stimulate ovulation within 24 h in all animals studied, as evidenced by recovery of ova from their oviducts as well as the presence of postovulatory follicles in their ovaries. Histologically, ovaries of animals receiving HCG exhibited atretic changes in most of the follicles smaller than 999 micrometer in diameter. Pregnant mares serum gonadotropin (PMSG, 10 IU) administered on days 9 and 10 of the cycle was not sufficient to stimulate ovulation in this species although histological changes in the follicular complement were observed. Administration of PMSG prior to the HCG appeared to have an inhibitory effect on ovulation induction. Follicles luteinizing with entrapped ova were seen in all groups receiving exogenous gonadotropin, although they were most prevalent in the animals receiving the maximum total gonadotropin doses (i.e. PMSG + HCG).

Effect of estrogen on sensitivity of rabbit bladder and urethra to phenylephrine.

The sensitivity of alpha-adrenoceptors to phenylephrine as indicated by the ED50 of the rabbit bladder and urethra was compared for segments in vitro from control (estrous), ovariectomized, ovariectomized-estrogen-treated, and pregnant animals. In control animals there was a trend for urethral segments to be more sensitive to phenylephrine (lower ED50) than bladder segments. This difference was abolished by castration, which decreased the sensitivity of the anular urethral segment, and by pregnancy, which tended to enhance the sensitivity of the bladder. The tension generated by bladder segments was enhanced by pregnancy and tended to be decreased by castration. The effects of castration tended to be reversed by treatment with estrogen (1 microgram per kg of body weight per day for 14 days). These data indicate that estrogen can influence the response of the urethra and urinary bladder to alpha adrenergic stimulation.

Post-ovulatory changes in the water content and inulin space of the rabbit oviduct.

Measurement of the water content and inulin space of the tissues of the ampulla, ampullary-isthmic junction and proximal isthmus showed that the loss of oedema was related to the position of the ova, whether this was normal (after hCG), delayed (by oestrogen treatment) or accelerated (by progesterone treatment).

Spike bursts in rabbit oviduct. I. Effect of ovulation.

Electrical activity of rabbit oviducts was recorded in vitro at 18, 24, and 68 h after injection of human chorionic gonadotropin. An array of eight suction electrodes 1-2 mm apart was moved sequentially to cover nearly the whole oviduct. The frequency of spike bursts, pacemaker frequency, percentage of nonpropagating bursts, and probability of propagating in the uterine direction varied steeply within a few millimeters along the oviduct. On the average, spreading was only slightly prouterine. Compared to 18 and 24-h, 68-h oviducts showed higher frequency of activity and longer distances of propagation, particularly in the isthmus. The activity extended to 65.8 and 69.6% of the distance from the fimbriae at 18 and 24 h, respectively, and at 68 h to 70.8% and 84.6% in those oviducts that contained and did not contain ova, respectively. Ova were recovered on the uterine side of the border of activity or in regions in which the percentage of nonpropagating bursts was high or, at 18 and 24 h, in segments containing local regions of inactivity. Apparently, frequency of activity, the degree to which propagation of activity deviates from randomness, and the length of the inactive area regulate the location of ova in the isthmus.

Spike bursts in rabbit oviduct. II. Effects of estrogen and progesterone.

Electrical activity of rabbit oviducts was recorded in vitro at 48 h after injection of human chorionic gonadotropin (HCG), 18 or 24 h after HCG with progesterone pretreatment, and 48 or 68 h after HCG with estrogen treatment 24 or 0 h after HCG, respectively. Frequency of spike bursts, pacemaker frequency, percentage of nonpropagating bursts, and probability of propagating in the uterine direction were obtained. Estrogen treatment decreased frequency of activity; at 48 h distance of propagation was increased and activity extended to 72.4% of the length of the oviduct compared to 65.7% in oviducts removed 48 h after HCG without estrogen. Only the ampullary-isthmic junction was active at 68 h after estrogen and HCG injection. Progesterone increased frequency and imposed a uterine bias, and activity extended to 73.6% of the length of the oviduct. These data support the hypothesis that properties of activity in the active area and the location of the active-inactive border regulate the location of ova in the isthmus of the rabbit oviduct.

Endotoxin-induced acceleration of ovum transport in rabbits.

Salmonella enteritidis-Boivin endotoxin (1--20 microgram/kg) induced accelerated oviductal ovum transport in rabbits in a dose-related manner. Indomethacin prevented this effect. Levels of prostaglandin E and F in uterine vein blood increased following endotoxin injection.

Enflurane and uterine contractility in rabbits.

The effect of enflurane on uterine contractility was studied in sexually mature rabbits in which intrauterine balloon catheters had been implanted. Three animal groups were studied: untreated; treated with estrogen-progesterone; and 27 to 28 days pregnant. The effects of 1.5 percent or 3.0 percent enflurane were quantitated by measuring contraction frequency and amplitude during an anesthetically steady state. The effects of prior anesthesia with 1.5 percent enflurane on uterine responses to 1.5 IU oxytocin IV were also evaluated. Neither 1.5 percent of 3.0 percent enflurane altered contraction amplitude or frequency in the 3 groups of rabbits. However, the amplitude of the contractile response to oxytocin 30 minutes following enfluane was significantly depressed. The results indicate that, while the intact rabbit uterus under different hormonal influences is not depressed by 1.5 or 3.0 percent enflurane, its response to oxytocin following enflurane is decreased.

Accelerated ovum transport in rabbits induced by endotoxin II. Changes in oviductal smooth muscle activity.

Oviductal mortility, measured with open-ended perfused catheters in anesthetized animals injected with human Chorionic Gonadotropin (hCG), is depressed 2 h following endotoxin injection and returns to control levels by 3 h after endotoxin injection. This decrease in motility is prevented by indomethacin. Endotoxin did not affect spontaneous or phenylephrine (PE)-induced contractions of oviduct when it was added to the bathing medium of in vitro tissues. Oviductal segments removed 2 h after endotoxin (26 h after hCG) showed electrical activity confined to the ampullary-isthmic-junction (AIJ), where ova were located; the dose-response curve for PE was shifted to the right and the maximum contraction was depressed. Activity of tissues removed 4 h after endotoxin more closely resembled control tissues except that the maximum contraction to PE was depressed, ova had passed out of the oviduct and a proovarian bias in the isthmus was not present. The response of the oviduct to prostaglandins (PGs) in vivo is critically dependent on the previous exposure to PGs. In endotoxin-treated animals PGE then PGF levels increase and the decrease in motility coincides with increased PGE levels, but accelerated ovum transport with the return of motility and activation of the isthmus.

Effect of inhibitors of prostaglandin synthesis and metabolism on ovum transport in the rabbit.

Several drugs known to affect prostaglandin synthesis, release, or metabolism have been tested for their effects on ovum transport in the rabbit after systemic or local administration. Acceleration of transport was obtained with several drugs; among the most effective were benzydamine, a blocker of thromboxane production, and L11204, an inhibitor of prostaglandin metabolism.

Comparison of the effects of prostaglandins D2, F2alpha and E1 on spontaneous contractions of rabbit oviduct.

The effects of PGD2, PGF2alpha and PGE1 were studied on the circular muscle of post-ovulatory rabbit oviducts in vitro. PGE1 inhibited spontaneous contractile activity. Lower concentrations of PGD2 and PGF2alpha were stimulatory and higher concentrations were inhibitory. Since PGD2 may be produced in the oviduct, any hypothesis concerning the role of prostaglandins in the control of oviductal motility and ovum transport should include PGD2 as well as PGFs and PGEs.

Simulation of oviductal ovum transport.

The present note describes a Monte Carlo simulation of ovum transport in the rabbit oviduct. Ova execute a random walk through a one-dimensional oviduct and the jump probabilities at each point are obtained from in vitro electrical recordings of smooth muscle activity. Simulated transport are compared with experimental findings at 18 and 66-68 h after human chorionic gonadotropin injection.

Cyclic nucleotides and prostaglandins (PGs) produced by the rabbit oviduct: effects of estrogen treatment.

Levels of cyclic AMP and cyclic GMP have been measured in oviducts of rabbits killed 68 hr after injection of human chorionic gonadotrophin (HCG) to induce ovulation. cAMP and cGMP levels were higher in the isthmus than in the ampulla. Estrogen treatment given at the same time as HCG increased cGMP levels. Levels of PGE and PGF in blood draining the oviduct were low and showed no effect of estrogen treatment at 68 hr after HCG.

Effect of IUDs on uterine cyclic AMP rabbits.

PIP: IUDs were inserted into the uteri of 15 New Zealand White rabbits in order to observe the effect of IUDs on uterine cyclic AMP. Rabbits received either a plastic IUD, a plastic-copper IUD, or were untreated. After 1, 2, or 3 months, the uteri were removed and analyzed. In 3 animals, IUDs were removed after 2 months and uteri excised 1 month later. Cyclic AMP was measured in neutralized, acid-extracted supernatants by the radioimmunoassay procedure of Steiner et al. Cyclic AMP was significantly lower (p less than .04) in the uteri containing plastic or plastic-copper IUDs by 1 month and remained depressed for up to 3 months. Cyclic AMP levels returned to control values in animals in which the plastic IUD was removed at 2 months, but remained depressed after removal of the plastic-copper IUD. The delayed effect of Copper-containing IUDs on the return of fertility in the rabbit needs further study.^ieng