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An L-arginine-nitric oxide-cyclic guanosine monophosphate system exists in the uterus and inhibits contractility during pregnancy.

OBJECTIVE: Nitric oxide is synthesized from L-arginine and it causes relaxation of smooth muscle by elevating cyclic guanosine monophosphate levels. We hypothesized that an L-arginine-nitric oxide-cGMP system is present in the uterus and modulates contractility. STUDY DESIGN: Isometric tension of the uterus was measured in vitro from pregnant rats in response to various agents that modulate nitric oxide-cyclic guanosine monophosphate production or action. RESULTS: Major findings are as follows: (1) The substrate and a donor of nitric oxide produced uterine relaxation; (2) inhibitors of the nitric oxide-cyclic guanosine monophosphate pathway blocked the relaxation responses; (3) nitric oxide synthase was localized to several uterine cell types; (4) nitric oxide was produced by the uterus during periods when L-arginine was consumed and citrulline levels increased; (5) effects of nitric oxide substrate on relaxation were mimicked by cyclic guanosine monophosphate; (6) nitric oxide-cyclic guanosine monophosphate responses were decreased during delivery; (7) L-arginine responses were increased by progesterone, and antiprogesterone treatment decreased cyclic guanosine monophosphate-induced relaxations. CONCLUSION: An L-arginine-nitric oxide-cyclic guanosine monophosphate system is present in the uterus and it may regulate relaxation during pregnancy. The inhibitory action of L-arginine and 8-bromo-cyclic guanosine monophosphate was considerably lower during delivery and post partum, indicating that the nitric oxide system may contribute to the maintenance of uterine quiescence during pregnancy, when progesterone levels are elevated, but not during delivery.

Amino Acid Oxidoreductases↗

Uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis: the University of Minnesota experience.

OBJECTIVE: To present the experience of a large referral center with patients with the rare but specific syndrome of uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis. DESIGN, PATIENTS: Between 1953 and 1991, 15 patients with the syndrome were evaluated by the authors; each patient's records were carefully reviewed. MAIN OUTCOME MEASURES: For each patient, the clinical course, specific anatomic findings, treatment(s) offered, and obstetrical outcome are presented. RESULTS: The specificity of the association of uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis was confirmed by our series, the largest in the literature to date. The findings suggest a specific development anomaly of the müllerian ductal system, probably secondary to a wolffian duct anomaly. The most common clinical presentation was that of the onset of pelvic pain and/or dysmenorrhea shortly after menarche, in association with the finding of a vaginal/pelvic mass. When a communication between the two sides existed, symptoms of abnormal vaginal discharge and bleeding were common. Optimal outcome appears to have occurred for patients initially managed using a conservative surgical approach, i.e., simple vaginal septum resection combined with conservative treatment of associated endometriosis. Obstetrical outcome in our patients was similar to that in patients with the more common combination of uterus didelphys and sagittal vaginal septum. CONCLUSION: A greater awareness of the syndrome of uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis should lead to its prompt diagnosis, allowing for early and appropriate surgical intervention as well as decreased long-term morbidity.

Adolescent↗

Unicornuate uterus and rudimentary horn.

OBJECTIVE: To evaluate clinical implications of the unicornuate uterus and rudimentary horn. DESIGN: A retrospective study. SETTING: A university hospital. PATIENT(S): Forty-two women who had a unicornuate uterus with or without rudimentary horn. INTERVENTION(S): The rudimentary horn was removed in 21 cases. MAIN OUTCOME MEASURE(S): Presence of other anomalies, fertility, and outcome of pregnancies were studied. RESULT(S): A right unicornuate uterus with noncommunicating rudimentary horn was the most common type of uterine anomaly. Unilateral renal agenesis was found in 13 (38%) of 34 cases. Six (14%) of the 42 patients had primary infertility. Thirty-four women produced 93 pregnancies; ectopic pregnancy (EP; rudimentary horn, tubal) occurred in 20 of these cases (22%). The pregnant uterine horn ruptured in 3 of 7 cases. Eight (57%) of the 14 women with infertility underwent treatment by IVF-ET; 4 of them conceived, and 2 had term delivery. The fetal survival rate was 61%, prematurity 17%, fetal growth retardation 5%, and the spontaneous intrauterine (IU) abortion rate was 16%. Pregnancy-induced hypertension (PIH) was more common in women lacking a kidney than in those with two kidneys. CONCLUSION(S): The high number of EPs indicates removal of rudimentary horn and its tube when diagnosed. The prognosis of IU pregnancy is not impaired in the unicornuate uterus although prematurity threatens. Unilateral renal agenesis is associated with PIH.

Abortion, Spontaneous↗

Congenital absence of the uterus and vagina is not commonly transmitted as a dominant genetic trait: outcomes of surrogate pregnancies.

OBJECTIVE: To determine the inheritance pattern of congenital absence of the uterus and vagina in affected women undergoing surrogacy IVF with this disorder. DESIGN: Retrospective study. SETTING: A hospital-based reproductive endocrinology and infertility center. PATIENT(S): Women diagnosed with congenital absence of the uterus and vagina undergoing IVF with subsequent transfer of embryos to a surrogate uterus. INTERVENTION(S): Questionnaires were sent to all infertility treatment centers performing surrogate procedures. MAIN OUTCOME MEASURE(S): Number, gender, and frequency of congenital anomalies in progeny. RESULT(S): Thirty-two of 53 surveyed programs responded (60%). One hundred sixty-two IVF cycles were performed, and 34 liveborn children were delivered (half female). No congenital anomalies were found, except for one male child with a middle ear defect and hearing loss. CONCLUSION(S): These results strongly suggest that congenital absence of the uterus and vagina, if genetically transmitted, is not inherited commonly in a dominant fashion.

Congenital Abnormalities↗

Tubal pregnancy in a unicornuate uterus with rudimentary horn: a case report.

OBJECTIVE: To report a case of tubal pregnancy in a unicornuate uterus with rudimentary horn on the side of the rudiment and its pathology. DESIGN: Case report. SETTING: University hospital. PATIENT: An 18-year-old woman, primigravida, with tubal pregnancy. INTERVENTION(S): Systemic administration of methotrexate, salpingectomy by laparotomy, and laparoscopic surgery for resection of rudimentary horn. MAIN OUTCOME MEASURE(S): Emergent laparotomy revealed that the intraperitoneal hemorrhage was caused by the rupture of the tubal pregnancy on the same side as the rudimentary horn of the unicornuate uterus. A corpus luteum was found at the ipsilateral ovary of the rudimentary horn. RESULT(S): Image diagnosis and pathological examination of the rudimentary horn revealed that this uterine malformation was a unicornuate uterus with a noncommunicated, noncavitary rudimentary horn, corresponding to class IIc of the American Fertility Society classification of müllerian anomalies. CONCLUSION(S): This is the first report of a tubal pregnancy on the side of the noncommunicating rudimentary horn with the ipsilateral ovary carrying a corpus luteum in a unicornuate uterus.

Abortifacient Agents, Nonsteroidal↗

Evidence for expression of estrogen receptor cofactor messenger ribonucleic acid in the ovary and uterus of domesticated animals (sheep, cow and pig).

Expression levels of estrogen receptor cofactors (coactivators or corepressors) in specific tissue compartments and cells are thought to influence the expression of estrogen responsive genes and thereby influence overall hormonal responsiveness of target tissues. To date, the presence of cofactors has been reported in tissues from humans, rats and mice. We analyzed the presence and distribution of messenger ribonucleic acids (mRNAs) encoding several transcriptional cofactors in the ovary and uterus of three domestic animal species, the sheep, cow and pig. Northern analysis for cofactors SRC-1, GRIP1, RAC3, p300, RIP140, and SPA showed expression in ovaries from all three species. In addition, lower expression of SRC-1, GRIP1, RAC3, p300, and RIP140 mRNAs was observed during the luteal phase (day 10-12 of the estrous cycle) than at estrus (day 0); however, SPA transcript levels remained unchanged. We then examined expression of mRNAs for changing (SRC-1, RIP140) and constitutively expressed (SPA) cofactors in ovine ovaries. SRC-1 and RIP140 transcripts in corpus luteum were lower compared to the surrounding ovarian tissue. SPA mRNA expression, however, was similar in corpus luteum and surrounding tissues. To determine which ovarian cell types express SRC-1, RIP140, and SPA, in situ hybridization was performed on sheep ovaries. Silver grains corresponding to these cofactors were seen in ovarian granulosa, theca and stromal cells, but appeared to be most abundant in the granulosa cells. Expression of SRC-1 and RIP140 in corpus luteum, however, was reduced compared to expression in follicular cells. Finally, we examined cofactor expression in ovine, bovine, and porcine uterus. Northern blot analysis for SRC-1, GRIP1, RAC3, p300, and RIP140 mRNAs showed higher expression in extracts of the endometrium compared to whole uterus. We provide the first evidence for the presence of estrogen receptor cofactor mRNAs in the ovary and uterus of three domestic animal species. We suggest that coactivators are conserved among species and associated with hormonal responsiveness of reproductive tract tissues in sheep, cow and pig.

Animals↗

Characterization of nitric oxide synthase activity in rabbit uterus and vagina: downregulation by estrogen.

Nitric oxide synthase (NOS) was determined in the soluble (cytosolic) and particulate fractions of rabbit uterus, vagina and cerebellum and the influence of estrogen treatment on NOS activity was studied. NOS in both the cytosolic and particulate fractions was highly calcium dependent. The activity in cytosolic fraction was nearly 4-fold higher than the particulate fractions from all three organs. The concentration of NOS was highest in cerebellum followed by vagina and uterus. Vaginal NOS activity was 3-4-fold higher than the uterine NOS. After a continuous treatment of rabbits for one week with estrogen, cytosolic NOS was reduced by nearly 7 and 4-fold in the uterus and vagina, respectively, whereas there was no significant change in the particulate NOS. Estrogen treatment caused no change in cytosolic or particulate NOS from the cerebellum. Downregulation of cytosolic NOS by estrogen in the estrogen target tissues like uterus and vagina and absence of effect in the cerebellum strongly suggests a physiological significance.

Animals↗

Effects of epinephrine and oxytocin on the release of prostaglandin F from the rat uterus in vitro.

Isolated uteri from rats with regular 4-day cycles were incubated in Krebs-Ringer bicarbonate buffer and the release of PGF into the medium was measured by radioimmunoassay after extraction of the incubation medium with ethyl acetate at pH 3.0-3.5. PGF was produced from endogenous precursors and accumulated in equal amounts in the medium during two successive 60 min periods on each day of cycle, but the magnitude of the production varied significantly during the cycle, being greatest in estrus. Oxytocin in doses up to 500 mU/ml had no effect on PGF accumulation in the incubation period at any stage of the cycle, while epinephrine (10(-3)) greatly stimulated PGF release from the estrous uterus but had no effect on PGF release from the diestrous uterus. Phentolamine, an alpha-blocking agent, had no effect on the epinephrine-induced release of PGF, while propranolol, a beta-blocking agent, not only prevented in increase in PGF production induced by epinephrine but also reduced the basal release of PGF by the estrous uterus. Since oxytocin contracts and epinephrine relaxes the nonpregnant rat uterus both in vivo and in vitro, it is unlikely that the effects of these two compounds on uterine contractility are mediated by the release of PGF2alpha.

Animals↗

Changes in regional blood flow in response to distension of the uterus in anaesthetised pigs.

The present study was undertaken in anaesthetised pigs to determine the primary reflex effects of distension of the uterus on the peripheral circulation. Experiments were performed in seven pigs anaesthetised with alpha-chloralose and artificially ventilated. Blood flow in the superior mesenteric, left renal and left external iliac arteries was assessed using electromagnetic flowmeters. Distension of the uterus was performed whilst preventing changes in heart rate and aortic blood pressure by injecting 20 ml of warm Ringer solution in a balloon positioned within the viscus (mean transmural pressure of about 18 mmHg). In each pig, distension of the uterus caused decreases in all measured blood flows. In four pigs, these decreases were graded by step increments of distension. In the seven pigs, the responses of decrease in mesenteric, renal and iliac blood flows were not affected by blockade of beta-adrenergic receptors with propranolol, but were abolished by the subsequent blockade of alpha-adrenergic receptors with phentolamine. The present study showed that distension of the uterus in anaesthetised pigs primarily caused reflex vasoconstriction in the mesenteric, renal and iliac vascular beds. This reflex response was mediated by sympathetic mechanisms which involved alpha vascular adrenergic receptors.

Adrenergic beta-Antagonists↗

Involvement of the pelvic plexus and the suprarenal ganglia in the neuropeptide Y (NPY) innervation of the cervix and the uterus of the rat.

The involvement of the pelvic plexus and suprarenal ganglia in the neuropeptide Y (NPY) innervation of the genital tract was studied in the female rat by means of denervation experiments and retrograde tracing studies. Removal of the paracervical ganglia caused a significant decrease of the NPY-immunoreactive nerve density and NPY concentration in the lower part of the genital tract: cervix, uterine body and lower part of the uterine horn. The decrease in NPY concentration in these three regions was more pronounced after lesion of the pelvic plexus. Lesion of the ovarian nerve plexus caused a depletion in the NPY-immunoreactive nerve fibres and a decrease in NPY concentration in the upper part of the uterine horn. Pelvic nerve section, inferior mesenteric ganglia excision and superior ovarian nerve section had no effect on the NPY innervation in the genital tract. Injection of fluorogold into the cervix and lower part of the uterus combined with immunohistochemistry revealed that 87.5% of labelled neurons in the pelvic plexus were NPY-immunoreactive. Following injection of fluorogold into the upper part of the uterus, 92% of labelled neurons in the suprarenal ganglia were NPY-immunoreactive. Treatment with 6-hydroxydopamine revealed that the NPY-immunoreactive nerve fibres were non-noradrenergic in the cervix, but were noradrenergic in the upper part of the uterus. In the uterine body and lower part of the uterine horn, both noradrenergic and non-noradrenergic NPY-immunoreactive nerve fibres were observed. These data demonstrate the major contribution of pelvic plexus neurons in the non-noradrenergic NPY innervation of the lower part of the genital tract, and the involvement of the suprarenal ganglia in the noradrenergic NPY innervation of the upper part of the uterus via the ovarian nerve plexus.

Animals↗

The effect of distension of the uterus on plasma renin activity (PRA) in anaesthetized pigs.

It has recently been shown that distension of the uterus in anaesthetized pigs causes reflex haemodynamic responses through efferent sympathetic mechanisms. The present study was undertaken to determine whether these mechanisms include activation of the renin-angiotensin system. The same methods were used in 14 pigs which were anaesthetized with alpha-chloralose and artificially ventilated. Balloons positioned within the uterus were distended for periods of 30 min by injecting 20 ml of warm Ringer solution. The responses of arterial blood pressure and heart rate were respectively prevented by blockade of alpha-adrenergic receptors with phentolamine and atrial pacing. Changes in plasma renin activity (PRA) were assessed during the last minute of distension by radioimmunoassay of angiotensin I. In each of 10 pigs, distension of the uterus (mean uterine transmural pressure of 17 mmHg) caused an increase in PRA in the absence of changes of interfering haemodynamic variables. In the remaining four pigs, this response was graded by step increments of the distension. The increase in PRA caused by uterine distension was abolished by bilateral section of the renal nerves (five pigs) or by blockade of beta-adrenergic receptors with propranolol. The present study showed that distension of the uterus in anaesthetized pigs primarily caused a reflex increase in PRA. This reflex response was mediated by renal nerves and involved beta-adrenergic receptors.

Adrenergic alpha-Antagonists↗

Impaired estrogen priming of progesterone receptors in uterus of MRL/MP-lpr/lpr mice, a model of systemic lupus erythematosus (SLE).

Estrogens exacerbate the autoimmune disease SLE and progesterone is immunoprotective. Estrogens increase synthesis of progesterone receptors (PR) and it is hypothesized that this physiological balance may be impaired in SLE. To test this, cytosolic PR were measured in hypothalamus, thymus and uterus from 6-week-old female ovariectomized BALB/c and MRL/MP-lpr/lpr mice 48 h after s.c. injection of estradiol benzoate (3.2 microg/0.1 ml; OB) in peanut oil or 0.1 ml peanut oil alone. PR were measured using [(3)H]ORG 2058, which does not bind to corticosteroid-binding globulin (CBG), and bound and free ligand were separated using minicolumns of Sephadex LH20 at 0 degrees C. PR were measured in cytosols from hypothalamus and uterus of oil-treated BALB/c mice, but were undetectable in thymus, whereas receptors were measurable in all three tissues of MRL mice. There was a significantly greater priming effect of OB on PR in uterus of BALB/c mice, but not in hypothalamus, and PR became detectable in thymus cytosols from BALB/c mice. Also, the apparent affinity of the binding reaction between [(3)H]ORG 2058 and PR was significantly higher than those measured in other tissues in hypothalamic cytosols of both strains. These results suggest that there is an impairment of estrogen priming of progesterone receptors in uterus and perhaps thymus of MRL mice.

Animals↗

Accuracy of three-dimensional transvaginal ultrasound in uterus volume measurements; comparison with two-dimensional ultrasound.

The purpose of this study was to document the accuracy of 3-D uterus volume and to compare it with 2-D measurements. Transvaginal ultrasound (US) examinations were performed in 48 consecutive patients before hysterectomy. The examinations were stored digitally on an internal disk drive for subsequent measurements in virtual organ computer-aided analysis (VOCAL) program. Immediately after the hysterectomy, the true volume was measured in a water bath. A total of 5 patients were excluded due to difficulty of identifying the borders of their uterus; 8 patients were excluded because of too large fibroids or diffuse hypertrophic enlargement of uterus (volume > 220 mL). Although the volumes estimated by the 3-D method were not significantly different (p = 0.126 first measurement, p = 0.561 second measurement), the volumes estimated by the 2-D method were significantly different (p = 0.005 first measurement, p = 0.012 second measurement). The mean error rates of the two 3-D volume measurements by the same observer were 7.4% and 7.9%, and they were 22.2% and 21.0% for the 2-D volume measurements. It may be concluded that the volume of the uterus can be measured more accurately by 3-D US than by 2-D US.

Adult↗

[Management of ten patients with complete septate uterus: hystersocopic section of and obstetrical outcome].

INTRODUCTION: Septate uterus is the principal müllerian anomaly, but complete septate uterus is uncommon and often associated with frequent obstetrical complications. Surgical section of the septum is however possible. MATERIAL AND METHOD: We report patients with a complete septum uterus operated in our department between 2002 and 2006. We performed a hysteroscopic section of the cervical, uterine and vaginal septum at discovery of the anomaly. The accuracy of imaging exams, frequency of associated malformations, past obstetrical events and reproductive outcome post surgery were analyzed. RESULTS: The surgical technique was based on section of the cervical part with scissors and hysteroscopic section of the uterine septum; no perforation was noted. Four patients required a second procedure to achieve complete uterine section. Five patients became pregnant after surgery, 8 pregnancies are reported: 2 term delivery, 1 preterm delivery, 4 miscarriages and 1 ectopic pregnancy. CONCLUSION: Complete surgical section of the cervical and uterine septum in case of complete septum uterus is safe. However, we cannot conclude about the obstetrical benefit of this surgical technique. A longer follow-up is needed.

Adult↗

Escherichia coli strains isolated from the uterus and urinary bladder of bitches suffering from pyometra: comparison by restriction enzyme digestion and pulsed-field gel electrophoresis.

Pyometra (uterine inflammation with accumulation of pus in the uterus) is regarded as one of the most common illnesses in bitches. The ethiology and pathogenesis are complex with both hormonal and bacterial elements. The bacteria most frequently isolated from the uterine content is Escherichia coli. In this study, 84 E. coli strains from the uteri of 70 bitches suffering from the disease were examined and their DNA-profiles compared by restriction enzyme analysis and pulsed-field gel electrophoresis (PFGE). Through variations in DNA-profiles of the E. coli isolates, this study indicates that pyometra is caused by E. coli originating from the normal flora of the dogs and not by certain clones spread between animals.E. coli strains from the urinary bladder and the uterus of six of the bitches suffering from simultaneous urinary tract infection and pyometra were examined and compared as above. The DNA-profiles of the isolates from each of the six bitches were 100% identical. This study supports the theory suggesting that in cases of simultaneous urinary tract infection and E. coli pyometra, the urinary tract and uterus are infected with the same bacterial strain. To evaluate whether the uterus was infected with a single clone of E. coli or if multiple clones were present, eight to 16 colonies of E. coli isolated from pyometra samples from a further 10 bitches were examined. All bacterial colonies from the culture of the same bitch showed identical DNA-profiles. In 14 of the 70 bitches, two macroscopically different but biochemically identical E. coli colony types were isolated. The two colony types from the same bitch proved to have identical DNA-profiles in 13 cases and almost identical in the remaining bitch.

Animals↗

Limb anomalies among offspring of women with a septate uterus: a report of three cases.

A retrospective analysis of 467 births among 255 women with uterine malformations revealed that three (0.64%) newborns had limb reduction defects. Two women had a subseptate uterus and one a complete septate uterus with a longitudinal vaginal septum. One newborn had a bilateral split hand and split foot, one had absence of left hand and wrist. One infant born without left hand, wrist and one antebrachial bone associated with omphalocele and diaphragmatic hernia died during the neonatal period. An association between severe limb reduction defects and septate uterus is possible, although the mechanism is unclear. The findings indicate a need to evaluate the uterine cavity if a newborn has this invalid defect, and a detailed ultrasound examination of fetal limbs is warranted in a case of a pregnant septate uterus.

Adult↗

Cycle dependent variations in transfer of 133xenon from vagina to uterus in rats.

The possible existence of an oestrus cycle dependent on local transfer of 133xenon from vagina to uterus was investigated in anaesthetized rats. 133Xenon in saline was infused into the vaginal lumen of rats in oestrous (n = 7) and dioestrous (n = 10). The uterus was removed 3 min after the infusion and the radioactivity in the organ counted, after which the remaining radioactivity in vagina was measured. The results showed that the radioactivity increased in all uteri compared with that of the background. The average transfer, expressed as per cent transfer, from vagina in the dioestrous group (5.5%) was significantly higher (P < 0.01, Mann-Whitney) than in the oestrous group (1.4%). The results suggest that the rate of transfer from vagina to uterus depended on the oestrous cycle. Vaginal treatment of women with progesterone for example, may similarly induce high local concentrations in the uterus. Empirically this is already used after in vitro fertilisation, it may also prevent progesterone induced migraine in menopausal women. The possible cycle dependent variations in the transfer in women should be evaluated.

Administration, Intravaginal↗

Growth factors in the uterus: steroidal regulation and biological actions.

Rapid progress has been made within the last 5-6 years in characterizing polypeptide growth factors in uterine tissues and fluids. There is convincing evidence that their synthesis and/or secretion is regulated by steroid hormones. The possibility that these growth factors play a central role in growth and development of the uterus or placenta is suggested by the presence of their receptors on uterine or placental cells and their stimulatory effects on these cells in vitro. Since growth factors interact synergistically and also have non-mitogenic functions, the presence of a variety of these factors in the uterus suggests that they probably regulate various aspects of uterine function through complex autocrine and paracine pathways. However, experimental models need to be designed that will permit a more detailed analysis of the actual role of these factors in utero. Fruitful approaches may be to administer neutralizing antibodies or blocking peptides so as to antagonize uterine growth factor action, or to develop appropriate transgenic animals. These and other lines of study should help us to understand the role of growth factors in development of the immature uterus, growth of the placenta or gravid uterus, repair and angiogenesis of the endometrium, and uterine pathology.

Animals↗