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Term pregnancy at the site of atresia following vaginal canalization in a case of uterus didelphys with hemivaginal atresia and ipsilateral renal agenesis.

OBJECTIVE: Uterus didelphys with hemivaginal atresia and ipsilateral renal agenesis is a rare syndrome of müllerian anomalies. Term pregnancy at the site of atresia is even rarer. CASE REPORT: A 28-year-old married woman presented with menometrorrhagia and primary infertility. Pelvic examination led to the suspicion of a pelvic mass between the uterus and bladder, and protruding to the right site of the paracervix. Ultrasound and magnetic resonance imaging examination revealed a left ovarian teratoma, right hematocolpos, and uterus didelphys with atresia of the right vagina and ipsilateral renal agenesis. Enucleation of the left ovarian teratoma by laparoscopy and drainage of hematocolpos by 2-cm canalization as a marsupialization procedure at the right paracervical protruding part under sonographic guidance were performed. Thereafter, a term pregnancy in the affected side was achieved. The patient underwent cesarean section due to breech presentation. CONCLUSION: A greater awareness of the syndrome of uterus didelphys, hemivaginal atresia, and ipsilateral renal agenesis should lead to a correct diagnosis. We herein report our experience with the correct diagnosis and alternative management of this rare syndrome.

Adult↗

Laparoscopic ultrasonography for uterovaginal canalization of a didelphic uterus with agenetic cervix.

Mullerian duct anomaly is often characterized by any of a number of disorders of the outflow tract and uterus. A 17-year-old woman suffered from cyclic lower abdominal pain for 3 years. Pelvic examination showed a small uterus with blind-ended vaginal canal about 3 cm in length. Three-dimensional pelvic ultrasonography showed a compact uterine corpus with fundal notch regarded as bicornuate uterus, and no evidence of uterine cervix. The same features were also proved by magnetic resonance imaging. Intraoperative ultrasonography showed a small uterine cavity, and uterovaginal canalization was performed. The patient had regular menses without further low abdominal pain after 6 months of follow-up. Uterovaginal canalization with the aid of intraoperative ultrasonography may be effective in managing the difficult didelphic uterus with an agenetic cervix and hypoplastic vagina.

Adult↗

Uterovaginal canalization and endometrial ablation of the obstructed uterine horn with hypoplastic cervix in the didelphic uterus.

Maldevelopment of the mullerian duct system may result in various urogenital anomalies including didelphic uterus with a hypoplastic cervix. Two women with this anomaly experienced symptoms including recurrent lower abdominal pain off and on of 1 to 2 years' duration. Magnetic resonance imaging revealed a double uterus with right hematometrium both patients. After hysteroscopic identification of hypoplasia of right uterine cervix, laparoscopic resection of the hematosalpinx, followed by uterovaginal canalization and prophylactic endometrial ablation of the right uterus was successfully performed by resectoscope. Normal menstruation ensued during follow-up of 18 and 24 months, respectively. Our experience suggests that uterovaginal canalization with prophylactic endometrial ablation may be an efficacious alternative to hysterectomy for management of didelphic uterus with a hypoplastic cervix. (J Am Assoc Gynecol Laparosc 8(1):151-153, 2001)

Abdominal Pain↗

Involvement of adrenoceptors in the ovarian vascular pedicle in the regulation of counter current transfer of steroid hormones to the arterial blood supplying the oviduct and uterus of pigs.

1. On Day 10 of the oestrous cycle in pigs, after laparotomy noradrenaline (NA), methoxamine (alpha 1-adrenomimetic, M), Prazosin (alpha 1-adrenolytic, Pr) in total doses of 4 mumol, and saline were infused (10 min) into the superficial layer of mesovarium on both sides of the ovarian pedicle vasculature, close to the ovary. 2. Blood flow in the ovarian artery, heart rate and progesterone (P4) and androstenedione (A4) secretion from the ovary and their concentrations in the ovarian venous effluent, as well as the concentrations of P4 and A4 in the blood supplying the oviduct and the uterus, were determined. 3. A significant increase of P4 and A4 secretion after NA and M infusion and increased concentrations of P4 and A4 in the ovarian venous effluent were found, but these changes did not influence the counter current transfer of hormones from the venous effluent into arterial blood supplying the oviduct and the uterus. 4. Infusion of Pr caused a significant decrease of P4 and A4 secretion and their concentrations in the ovarian venous effluent and significantly increased A4 concentration in the blood supplying the oviduct and uterus. 5. The results indicate that stimulation of alpha 1-adrenoceptors in the area of ovarian vasculature did not influence, whereas block of alpha 1-adrenoceptors affected, the local concentration of steroid hormones in the blood supplying the oviduct and the part of the uterus proximal to the ovary, despite the changes in the concentrations of steroid hormones in the ovarian effluent.

Adrenergic alpha-Agonists↗

Inhibition by oestrogen of collagen breakdown in the involuting rat uterus.

1. Both the post-partum involution of the rat uterus and the rapid breakdown of collagen that accompanies it are extensively inhibited by oestrogenic hormones. In the normal rat, 85% of the uterine collagen is degraded within 4 days after parturition; in rats treated with 100mug. of 17beta-oestradiol/day, only 35% of uterine collagen is broken down in the same period. 2. Similar effects are produced by diethylstilboestrol if the dose is increased tenfold. 3. Collagen breakdown is inhibited to a greater extent than is the loss of wet weight by oestradiol but not by diethylstilboestrol. 4. The oestrogens appear to act by blocking the breakdown of collagen. There is a greatly decreased concentration of free hydroxyproline in the uterus of treated animals. 5. Acid hydrolase concentrations (beta-glucuronidase, beta-galactosidase, cathepsin D and acid phosphatase) in the uterus are decreased by oestrogen treatment compared with controls, but the total amounts of these enzymes in the uterus are somewhat elevated. Oestrogens do not appear to inhibit collagen breakdown by altering the concentration and total amount of acid hydrolases.

Acid Phosphatase↗

Expression of angiotensinogen in the uterus induced by coagulating gland renin in mice.

Coagulating gland (CG) renin is one of the components of the local renin-angiotensin system (RAS), which plays important roles in the maintenance of homeostasis in several tissues. Although the existence of local renin has been reported in many tissues, its function is not yet well understood. In the present study, the relationship between CG renin and uterine angiotensinogen was investigated by immunohistochemical and in situ hybridization techniques. In mating experiments with male and female C57BL/6 mice, renin was demonstrated immunohistochemically on the epithelial cells of the uterus on the first day after coitus; however, it was not detected on the second and third days after coitus. Neither immunoreactive cells nor messenger signals for renin were demonstrated on the epithelial cells of the uterus throughout the experiments. On the first day after mating, it was noted that positive signals for angiotensinogen mRNA were expressed on the epithelial cells of the uterus in situ hybridization, but not on the second and third days after coitus. These results suggest the possibility that CG renin is transferred to the uterine epithelium at mating and temporarily activates the expression of angiotensinogen in the uterus. Angiotensin II produced by angiotensinogen may act as an important mediator for vascularization of the first step of pregnancy.

Angiotensinogen↗

Immunohistochemical studies on oestrogen receptor alpha (ER alpha) and the proliferative marker Ki-67 in the sow uterus at different stages of the oestrous cycle.

In order to better understand physiological changes during the different stages of the oestrous cycle, immunohistochemistry was used in the present study to investigate the distribution of oestrogen receptor alpha (ER alpha) as well as the proliferative marker Ki-67, in the sow uterus during the oestrous cycle. Uterine samples were collected from multiparous sows with normal reproductive performance at selected stages of the oestrous cycle: at late dioestrus (d 17), prooestrus (d 19), oestrous (d 1), early dioestrus (d 4) and dioestrus (d 11-12), respectively. The tissue samples were fixed in 10% formaldehyde, embedded in paraffin and subjected to immunohistochemistry using monoclonal antibodies against ER alpha (C-311) and Ki-67 (MM-1). In general, the immunostaining of both ER alpha and Ki-67 was confined to nuclei of the target cells. Variations were seen, not only at the different stages of the oestrous cycle, but also in the different tissue compartments of the uterus. In the epithelia, the strongest ER alpha staining and highest amount of positive Ki-67 cells were found at early dioestrus. In the myometrium, the highest levels of staining of both ER alpha and Ki-67 positive cells were found at pro-oestrus and oestrus. For the proliferative marker, Ki-67, no positive cells were found at dioestrus and late dioestrus in the epithelium and myometrium. In the connective tissue stroma (subepithelial layer), the highest number of ER alpha positive cells were found at oestrus, which was significantly different compared with other stages (p< or = 0.05), whereas the levels of Ki-67 positive cells were relatively low and did not differ between the stages examined. Significant correlations between the number of ER alpha positive cells in the stroma and Ki-67 positive cells in the epithelia were observed. This suggests indirect regulatory mechanisms on epithelial proliferation via ER alpha in the stroma. In conclusion, these findings in the sow uterus show that the presence of ER alpha as well as Ki-67 protein varies not only between different stages of the oestrous cycle but also between different tissue compartments of the uterus. These findings indicate various regulatory mechanisms and stress the importance of localising ER alpha and proliferating cells in different uterine tissues.

Animals↗

Color Doppler and gray-scale ultrasound evaluation of the postpartum uterus.

OBJECTIVES: To evaluate the color Doppler and gray-scale sonographic appearance of the uterus after pregnancy, with special attention to the occurrence of areas of enhanced vascularity and placental remnants. PATIENTS AND METHODS: Cross-sectional observational study involving 385 consecutive women presenting at their first visit after pregnancy. The uterus was evaluated using ultrasound with color Doppler. In the presence of placental remnants, blood was sampled for measurement of beta human chorionic gonadotropin (beta hCG), hemoglobin (Hb) and infectious parameters. If indicated, a dilatation and curettage was performed. RESULTS: In 8.3% of women, areas of enhanced vascularity were detected with color Doppler examination. Most cases (68.9%) were focal areas of one or more vessels. In 2.6% of patients abnormal vascularity extended over a large area of the whole myometrium. In 6.75% of cases, placental remnants were detected. In 46% of these, blood sampling revealed beta hCG levels below 30 mIU/mL; serological infection parameters and Hb concentration were within the normal range. CONCLUSIONS: Areas of enhanced vascularity of the uterus, ranging from a focal vascular pedicle to a larger area of the myometrium, are relatively common after pregnancy. They are predominantly seen in the presence of placental remnants, in the early postpartum period and after instrumental or manual delivery of the placenta. There are no clear risk factors for retained placental tissue, besides the history of blood transfusion in the early postpartum, and perhaps multigravidity. Serology is of little help in the diagnosis of retained gestational products. The knowledge of the ultrasound and color Doppler features of the uterus after pregnancy may prove of practical value for the management of abnormal uterine bleeding in the postpartum period.

Adolescent↗

Uterine artery embolisation for symptomatic fibroids: the effect of the large uterus on outcome.

OBJECTIVE: The aim of this study was to evaluate the efficacy of uterine artery embolisation (UAE) in myomatous uteri larger than 24 week's gestation (780 cm3). DESIGN: Prospective case control study. SETTING: Universitas Hospital, University of the Free State, Bloemfontein, South Africa. POPULATION: Sixty-one women, who underwent UAE, were included in the study. The study group comprised of 12 women with uteri > or =780 cm3 and the control group 49 women with uteri <780 cm3. METHODS: UAE was performed and the difference in outcome for the two groups was determined at 12 months. MAIN OUTCOME MEASURE: Symptomatic improvement with embolisation of the large uterus. RESULTS: Reduction of dysmenorrhoea, menorrhagia and pressure effects was similar for both groups. The median reduction in uterine volume (pre- to post-embolisation) was 188 cm3 (range 28-2038 cm3) with a 95% CI for the median difference for paired data of 146.5 and 236. Only 66% of the study group had, however, a reduction in volume to <780 cm3. The complication rates were similar for the two groups with regards to post-embolisation syndrome, fibroid slough, haematoma formation, infection, hysterectomy and failure to embolise. Satisfaction was similar between the two groups, with 91% of women satisfied with the procedure. CONCLUSION: The large uterus does not decrease UAE's efficacy. Although 33.3% of the study group still had a uterus of > or =780 cm3, symptom reduction was still similar for both groups. Women may thus still be left with a large uterine volume but without symptoms. This must be taken into consideration when counselling women with an extremely large uterus for UAE.

Adult↗

[Laparoscopic ante-fixation of the uterus--modification of the Menge operation].

Surgical antefixation of the retroflected uterus is today for several reasons a rare event. We report on a forty-year old patient with dyspareunia, dysmenorrhoea and lumbalgia. Elevation of the uterus by means of a Hodge pessary relieved her symptoms. This prompted laparoscopical suspension of the diagnosed retroflexio uteri mobilis. We used a modification of Menge's technique stitching the rotund ligament to the anterior surface of the uterus. This modified technique is especially useful because it can be performed easily by laparoscopy. In addition shortening of the round ligaments achieves a physiological position of the uterus in the pelvis without major changes in the pelvic anatomy.

Adult↗

[Diffuse cavernous myometric angiomatosis of the pregnant uterus and its clinical significance].

Sonography in the 5th month of pregnancy--the pregnancy itself appearing intact--revealed an enormous myometric angiomatosis affecting the body of the uterus. Hence, the size of the uterus in the 17th week of pregnancy equalled the size usually attained in the 36th week only. Tendency to collapse and pulselessness as a consequence of excessive haemorrhages into the enormously dilated veins was observed. The myometrium displayed varying intensity and was permeated by blood vessels of different sizes up to 1 cm diameter. Because of the extremely dangerous tendency of the uterine wall to break, hysterectomy was performed. The histological specimen showed a diffuse cavernous myometric angiomatosis of the body of the uterus and of the isthmus uteri. We believe that this extreme reaction of the veins during pregnancy is caused by a specifically acting agent and by a special disposition of the veins in the uterus. So far, only two cases have been described in literature (Halban, case 1 Kaufmann).

Adult↗

Steroid hormones augment nitric oxide synthase activity and expression in rat uterus.

Nitric oxide (NO) is synthesized in a variety of tissues, including rat uterus, from L-arginine by NO synthase (NOS), of which there are three isoforms, namely neuronal, endothelial and inducible NOS (nNOS, eNOS and iNOS, respectively). Nitric oxide is an important regulator of the biology and physiology of the organs of the reproductive system, including the uterus. Some studies have shown increased variation in NO production and NOS expression during the oestrous cycle. However, the factors that regulate NO production in the uterus remain unclear. Therefore, in the present study, we investigated the effect of sex steroids on NOS expression and activity in the ovariectomized rat uterus. Ovariectomized rats received progesterone (4 mg per rat) or 17beta-oestradiol (1 microg per rat). All rats were killed 18 h after treatment. Both progesterone and oestradiol were able to augment NOS activity. The effect of oestradiol was abolished by pre-incubation with 500 micro M aminoguanidine, an iNOS inhibitor, or by coadministration of oestradiol with 3 mg kg(-1) dexamethasone, but the effect of progesterone was not affected by these treatments. Uterine nNOS, eNOS and iNOS protein levels were assessed using Western blots. Ovariectomized rat uteri expressed iNOS and eNOS. Progesterone increased the expression of eNOS and iNOS, whereas oestradiol increased iNOS expression only. These results suggest that oestradiol and progesterone are involved in the regulation of NOS expression and activity during pregnancy and implantation in the rat.

Animals↗

The gene encoding multidrug resistance is induced and expressed at high levels during pregnancy in the secretory epithelium of the uterus.

A survey of the expression of the multidrug-resistance gene (mdr) in mouse tissues revealed that a mdr mRNA species is expressed at extremely high levels in the gravid uterus. mdr mRNA expression levels increase dramatically during pregnancy compared to the relatively low levels of expression observed in the nongravid uterus. In situ hybridization experiments revealed that the increased expression of the mdr mRNA is specifically localized to the secretory epithelial cells of the endometrium. Immunocytochemistry studies with a mdr glycoprotein-specific antiserum demonstrate that the mdr glycoprotein is predominantly localized to the luminal surface of the secretory epithelial cells. These results indicate that the mdr gene expression in the uterus is controlled by the physiologic changes associated with pregnancy. Our data are consistent with a potential role for the mdr glycoprotein in the transport of substrate across the secretory epithelium of the gravid uterus.

Animals↗

Cannabinoid ligand-receptor signaling in the mouse uterus.

Using RNA (Northern) blot hybridization and reverse transcription-PCR, we demonstrate that the brain-type cannabinoid receptor (CB1-R) mRNA, but not the spleen-type cannabinoid receptor (CB2-R) mRNA, is expressed in the mouse uterus and that this organ has the capacity to synthesize the putative endogenous cannabinoid ligand, anandamide (arachidonylethanolamide). The psychoactive cannabinoid component of marijuana--delta 9-tetrahydrocannabinol (THC)--or anandamide, but not the inactive and nonpsychoactive cannabidiol (CBD), inhibited forskolin-stimulated cyclic AMP formation in the mouse uterus, which was prevented by pertussis toxin pretreatment. These results suggest that uterine CB1-R is coupled to inhibitory guanine nucleotide-binding protein and is biologically active. Autoradiographic studies identified ligand binding sites ([3H]anandamide) in the uterine epithelium and stromal cells, suggesting that these cells are perhaps the targets for cannabinoid action. Scatchard analysis of the binding of [3H]WIN 55212-2, another cannabinoid receptor ligand, showed a single class of high-affinity binding sites in the endometrium with an apparent Kd of 2.4 nM and Bmax of 5.4 x 10(9) molecules per mg of protein. The gene encoding lactoferrin is an estrogen-responsive gene in the mouse uterus that was rapidly and transiently up-regulated by THC, but not by CBD, in ovariectomized mice in the absence of ovarian steroids. This effect, unlike that of 17 beta-estradiol (E2), was not influenced by a pure antiestrogen, ICI 182780, suggesting that the THC-induced uterine lactoferrin gene expression does not involve estrogen receptors. We propose that the uterus is a new target for cannabinoid ligand-receptor signaling.

Animals↗

Insulin-like growth factor-1 (IGF-1) receptor-insulin receptor substrate complexes in the uterus. Altered signaling response to estradiol in the IGF-1(m/m) mouse.

Some of the actions of estradiol occur through stimulation of growth factor pathways in target organs. Tyrosine-phosphorylated (Tyr(P)) insulin-like growth factor-1 receptor (IGF-1R) and the insulin receptor substrate (IRS)-1 are found in the uterus of mice treated with estradiol. Immunoprecipitates of uterine Tyr(P) IRS-1 contained both p85, the regulatory subunit of phosphatidylinositol (PI) 3-kinase, and PI 3-kinase catalytic activity. Estradiol also stimulated binding of IRS-1 and PI 3-kinase to the IGF-1R. Depletion of IRS-1 from uterine extracts reduced PI 3-kinase associated with the receptor, which suggests that binding of the enzyme to IGF-1R occurs primarily in a complex that also contains IRS-1. Following treatment with estradiol, formation of Tyr(P) IGF-1R, Tyr(P) IRS-1, and the p85.IRS-1 complex was very weak in the uterus of IGF-1(m/m) mice, which are severely deficient in IGF-1. This indicated that most, if not all, of the estradiol-stimulated Tyr phosphorylation of uterine IRS-1 originates from ligand activation of IGF-1R kinase. IRS-2 was also Tyr-phosphorylated in the normal uterus and bound more IGF-1R and p85 in response to estradiol; however, a marked decrease in levels of uterine IRS-2 occurred 12-24 h after treatment with estradiol. Since IRS-2 was present in IGF-1R precipitates and a recombinant form of IGF-1 (long R3 IGF-1) stimulated formation of Tyr(P) IRS-2, hormonal activation of this docking protein probably occurs through the IGF-1R. In summary, our findings show that estrogen activation of uterine IGF-1R kinase results in enhanced binding of p85 (PI 3-kinase) to IRS-1 and IRS-2. The formation of one or both of these complexes may be important for the potent mitogenic action of this steroid. That estradiol stimulated a decrease of IRS-2, but not of IRS-1, suggests that these docking proteins have different roles in hormone-induced signaling in the uterus.

Adaptor Proteins, Signal Transducing↗

Estrogen-dependent production of erythropoietin in uterus and its implication in uterine angiogenesis.

Although erythropoietin (Epo) has been shown to possess in vitro angiogenic activity, its physiological significance has not been demonstrated. Normally angiogenesis does not occur actively in adults but an exception is the female reproductive organ. In the uterine endometrium, angiogenesis takes place actively for supporting the endometrial growth that occurs during transition from the diestrus to estrous stage. This transition is under control of 17beta-estradiol (E2), an ovarian hormone, and can be mimicked by injection of E2 to ovariectomized (OVX) mouse. Thus, the uterus is a pertinent site to examine the Epo function in angiogenesis. We found that Epo protein and its mRNA were produced in an E2-dependent manner, when the uterus from OVX mouse was cultured in vitro. The de novo protein synthesis was not needed for E2 induction of Epo mRNA. Administration of E2 to OVX mouse induced a rapid and transient increase in Epo mRNA in the uterus. Injection of Epo into the OVX mouse uterine cavity promoted blood vessel formation in the endometrium. Furthermore, injection of the soluble Epo receptor capable of binding with Epo into the uterine cavity of non-OVX mouse in diestrus stage inhibited the endometrial transition to proestrus stage, whereas heat-inactivated soluble Epo receptor allowed the transition to occur. These results, combined with our finding that the endothelial cells in uterine endometrium express Epo receptor, strongly suggest that Epo is an important factor for the E2-dependent cyclical angiogenesis in uterus.

Animals↗

Magnetic resonance imaging in the evaluating of double uterus and associated urinary tract anomalies: a report of five cases.

Uterine anomalies are associated with unilateral renal aplasia. We present the MR features of five cases with 'double' uteri. The anomalies consisted of four cases of uterus didelphys and one of a complete septate uterus. All the cases with uterus didelphys also had a longitudinal vaginal septum. The MR diagnoses were confirmed with hysterosalpingography and with laparoscopy. In one case of didelphic uterus, MR images predicted the (three-dimensional helical) computer tomography (CT)-pyelographic diagnosis of renal aplasia in which the single kidney was normal. The study shows that MR is a valuable tool for the diagnosis of not only uterine anomalies but also associated anomalies in other systems.

Abnormalities, Multiple↗

Implantation, transplantation, and epithelial-mesenchymal relationships in the rat uterus.

Free tail skin grafts or suspensions of viable epidermal cells have been placed in the atraumatized uterus of isologous rat hosts and allowed to "implant" of their own accord to study the possible uniqueness of this site for other than nature's transplants, i.e. conceptuses, and its response to unnatural grafts. Despite the presence of an intact endometrial epithelium, free skin grafts heal-in rapidly, provided that a state of estrogen excess is established at the time of transplantation. In the absence of estrogen most of the grafts failed to implant. Once established, the grafts survive indefinitely without further estrogen. However, if at any stage a state of continual estrus is established, skin epidermis migrates centrifugally from the graft perimeter invasively replacing the native uterine epithelium. The results of an analysis of the modus operandi of this estrogen-facilitated epidermal migration in utero sustain the view that the hormone acts upon the uterine stroma rather than upon the epidermal cells. When grafts of lingual mucosa or vaginal "skin" were placed in the uteri of rats maintained in chronic estrus, migration of epidermis took place even more vigorously than from tail skin. These epithelia conserved their distinctive histologic specificities indefinitely when growing as heterotypic recombinants on the alien mesenchymal stroma of the uterus. Monodisperse suspensions of epidermal cells appear to "implant" and establish small epidermal plaques in the uterus only at sites predestined to accept conceptuses. That the endocrinologic parameters for the establishment of skin grafts in the uterus are similar to those for blastocysts is suggested by the finding that both kinds of graft can become established in the same uterine horn in the absence of exogenous hormones.

Animals↗