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The Fallopian tubes in domestic mammals: how vital is their physiological activity?

Set in an historical perspective, this essay examines diverse physiological aspects of Fallopian tube function in domestic animals and man. Microsurgical experiments are described that established the role of the isthmus in imposing a sperm gradient up to the site of fertilisation. Resection of the isthmus followed by reanastomosis of the remaining portions of the tube generated a high incidence of polyspermy in mated animals. Scanning electron microscopy and surgical studies revealed that spermatozoa were arrested and stored in the caudal portion of the isthmus before ovulation, the so-called functional sperm reservoir. There were specific adhesion contacts between the sperm head and endosalpingeal microvilli or cilia. Further experiments indicated that very large numbers of competent spermatozoa could be released from pre-ovulatory binding by microinjections of a solution of progesterone in oil under the serosal layer of the tube: when suitably timed, such treatment led to a high incidence of polyspermic fertilisation. Avid sperm binding in the caudal isthmus before ovulation prevents myosalpingeal activity leading to abnormal fertilisation, as might occur with multiple mating. Temperatures in the reproductive system were assessed and the caudal isthmus was found to be cooler than the ampulla during the pre-ovulatory phase of sperm storage. Finally, the existence of fluid microenvironments within the Fallopian tubes was reported, and the role of suspended cumulus-corona cells in amplifying signals from the zygote examined. An impact of Fallopian tube fluids on embryonic gene expression was also considered--an influence that may be further imposed if such fluids have access to the uterine lumen.

Animals↗

Vascular endothelial growth factor localization in human ovary and fallopian tubes: possible role in reproductive function and ovarian cyst formation.

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that also increases vascular permeability. We hypothesized that VEGF plays a role in the regulation of cyclic ovarian angiogenesis in women, and that its ability to increase vascular permeability may be an important factor in the production of fallopian tube effluent and fluid formation in ovarian cysts. To examine these hypotheses, we assessed VEGF expression in ovaries and fallopian tubes from premenopausal (n = 10) and postmenopausal (n = 4) women. Immunohistochemical analysis for VEGF was performed using a rabbit polyclonal antibody directed against human VEGF. In normal ovaries from premenopausal women, VEGF within healthy follicles was localized to the thecal cell layer, with minimal VEGF peptide detected in the granulosa cell layer. VEGF was not expressed in atretic follicles or a degenerating corpus luteum. However, intense VEGF immunostaining was observed within the highly vascularized corpora lutea in all specimens examined. In normal ovaries from postmenopausal women, VEGF was detected only in epithelial inclusion cysts and a serous cystadenoma. In specimens from both pre- and postmenopausal women, the luminal epithelium of the fallopian tube as well as smooth muscle cells and pericytes lining small and large blood vessels within the tube and hilum of the ovary exhibited specific staining for VEGF. Based on these data, we suggest that during reproductive life, VEGF plays a role in the growth and maintenance of the ovarian follicle and corpus luteum by mediating angiogenesis. In addition, VEGF within the fallopian tube luminal epithelium may increase vascular permeability and modulate tubal luminal secretions. Similarly, VEGF in the epithelial lining of benign ovarian neoplasms may contribute to fluid formation in ovarian cysts.

Adult↗

Molecular evidence for putative tumour suppressor genes on chromosome 13q specific to BRCA1 related ovarian and fallopian tube cancer.

BACKGROUND/AIMS: Loss of heterozygosity (LOH) on chromosome 13q has been reported to occur frequently in human ovarian cancer, and indications have been found that chromosome 13 may also play a specific role in the inherited form of ovarian cancer. The aim of this study was to define regions on chromosome 13 that may harbour additional tumour suppressor genes involved in the tumorigenesis of BRCA1 related ovarian and fallopian tube cancer. MATERIALS/METHODS: DNA extracted from paraffin wax blocks of 36 BRCA1 associated ovarian and fallopian tube carcinomas was analysed by LOH polymerase chain reaction using seven highly polymorphic microsatellite markers spanning chromosome 13q. RESULTS: High LOH frequencies were found on loci 13q11, 13q14, 13q21, 13q22-31, 13q32, and 13q32-4, suggesting the presence of putative tumour suppressor genes on the long arm of chromosome 13 that may play a role in the pathogenesis of BRCA1 related ovarian and fallopian tube cancer. LOH patterns appeared to be independent of the type of BRCA1 mutation, stage, and grade. Although in some cases there were indications for loss of larger parts of chromosome 13, in most cases losses were fairly randomly distributed over chromosome 13 with retained parts in between lost parts. Microsatellite instability was found in six cases. CONCLUSION: Several loci on chromosome 13q show high frequencies of LOH in BRCA1 related ovarian and fallopian tube cancer, and may therefore harbour putative tumour suppressor genes involved in the carcinogenesis of this particular type of hereditary cancer.

Chromosomes, Human, Pair 13↗

Immunocytochemical localization of growth factors and their receptors in human pre-embryos and Fallopian tubes.

We utilized indirect immunocytochemistry to demonstrate the presence of growth factors and their receptors in human pre-embryos and Fallopian tubes. In pre-embryos, only transforming growth factor-alpha (TGF-alpha) and the intracellular domain of epidermal growth factor receptor (EGFR) were found at the 4-cell stage. In 8- to 14-cell pre-embryos, TGF-alpha, the intracellular and extracellular domains of EGFR, and insulin-like growth factor-I and its receptor were found. Antibodies against TGF-alpha stained all Fallopian tube specimens, while the extracellular domains of EGFR was only found in specimens from patients with either blood type A or AB. These results suggest a cross-reactivity between the extracellular domain of the EGFR and blood group antigens. Our novel demonstration of growth factor receptor staining in human pre-embryos shows that growth factor receptor localization is dependent on the developmental stage of human pre-embryos. We have also established a potentially important link between the Fallopian tube which secretes growth factors and the localization of growth factor receptors in pre-embryos. These findings are compatible with the hypothesis that tubal secretions are embryotrophic for the early development of the pre-embryo.

Adult↗

Radionuclide hysterosalpingography for evaluation of fallopian tube patency.

A prospective study was undertaken to evaluate the efficacy of radionuclide hysterosalpingography (RNHSG) using a technique with some modifications, that was described by Iturralde and Ventner (1). As these investigators demonstrated, technetium-labeled human albumin microspheres (HAM) will normally migrate spontaneously from the vagina to the ovaries. This study confirms that in the presence of fallopian tube obstruction, fibrosis and/or lack of motility, this migration does not take place, and that the presence or absence of migration of HAM can be imaged with a gamma camera. In the evaluation of 52 tubes we found that the efficiency of RNHSG for evaluation of fallopian tube patency when compared with contrast hysterosalpingography and/or direct observation of surgical pathology was over 94%. RNHSG is an essentially innocuous technique for assessing functional and mechanical fallopian tube obstruction that can be performed with conventional nuclear imaging equipment.

Evaluation Studies as Topic↗

Follicle-stimulating hormone receptor is expressed in human ovarian surface epithelium and fallopian tube.

The cellular expression of pituitary gonadotropin receptors in gonadal tissues is poorly defined because of the lack of suitable reagents. In this study, we developed in situ hybridization and reverse transcription polymerase chain reaction techniques for the evaluation of follicle-stimulating hormone receptor (FSHR) expression in the ovary and fallopian tube. Using a single-strand RNA probe, we demonstrated that FSHR mRNA expression is strongest in Graafian follicles. Within these developing follicles, granulosa cells showed the greatest expression, although both theca interna and theca externa were also positive, interna greater than externa. Granulosa cells in both primary and primordial follicles were positive, with primordial follicles showing only weak focal positivity. Ovarian surface epithelium and fallopian tube epithelium, not previously recognized to express FSHR, were both strongly positive. The FSHR expression in the ovary and fallopian tube was confirmed by reverse transcription polymerase chain reaction. Our results indicated that the FSHR is expressed in a cell-specific fashion at different stages of follicular development and is also expressed in ovarian surface and fallopian tube epithelia. The presence of FSHR in ovarian surface epithelium and of gonadotropin-binding sites in ovarian neoplasms provide additional evidence supporting the derivation of epithelial ovarian tumors from the surface epithelium and should promote heightened interest in the gonadotropin theory of ovarian tumorigenesis. More importantly, this study shows the feasibility of evaluating FSHR expression by both in situ hybridization and reverse transcription polymerase chain reaction. Application of these techniques to tumor specimens will help to elucidate the role of gonadotropins and their receptors in the carcinogenesis of gynecological tumors.

Base Sequence↗

Second-look laparotomy in fallopian tube carcinoma.

From August 1974 through August 1980, eight patients with primary fallopian tube carcinoma underwent second-look laparotomies at The University of Texas M.D. Anderson Hospital and Tumor Institute. Prior to the second-look laparotomies all patients were clinically free of disease. Initial treatment consisted of surgery and chemotherapy for four of these patients, surgery and radiation therapy for two patients, and surgery, radiation therapy, and chemotherapy for two patients. The second-look laparotomies showed five patients were free of disease, one patient had microscopic residual disease, and two patients had persistent macroscopic disease. Recurrences following negative second-look laparotomies developed in two patients. One recurrence occurred at 41 months after the procedure and the other 69 months afterward. Both patients lived more than 5 years after the second-look laparotomies were performed. Three patients with negative findings at second-look procedures and the patient with microscopic residual disease remain clinically free of disease 34, 53, 74, and 50 months after the laparotomies, respectively. Following additional chemotherapy, the two patients who evidenced macroscopic disease at the second-look procedure died 16 and 32 months following the second-look laparotomies. The second-look findings can be used to predict disease behavior and may have a role in the management of patients with fallopian tube carcinoma.

Adult↗

Psammoma bodies and cells from in situ fallopian tube carcinoma in endometrial smears: a case report.

BACKGROUND: Primary in situ fallopian tube carcinomas are rarely diagnosed, and malignant cells from this lesion have not been previously described as occurring in endometrial smears. CASE: A 57-year-old, postmenopausal woman had an endometrial smear that revealed adenocarcinoma cells associated with psammoma bodies. She also had smooth muscle cells in the smear compatible with uterine leiomyomas. Examination of the hysterectomy specimen disclosed a primary in situ carcinoma of the left fallopian tube and uterine leiomyomatosis. CONCLUSION: Endometrial cytology plays an important role in the diagnosis of pathologic processes in the uterus. It may also contribute useful information on extrauterine diseases.

Adenocarcinoma↗

Variations of lysosomal enzymes in different parts of rabbit Fallopian tube during ovum transport.

Some lysosomal enzymes (viz., acid DNase, acid RNase and beta-glucuronidase) were estimated in different parts of the rabbit Fallopian tube during different hours post coitum (p. c.). At estrus, alterations of acid RNase and beta-glucuronidase were observed in different anatomical segments of the Fallopian tube but acid DNase was undetectable. When these enzymes were compared at different hours p.c., it was noticed that when the ovum reaches ampullary (A), ampullary-isthmic junction (AIJ) and isthmic (I) segments of the Fallopian tube at the respective hours 14, 24 and 70, the acid DNase activity showed increased value in these parts when compared to their preceding groups. Acid RNase also showed similar type of pattern except that it was not altered at 14 hr p. c. At 144 hr p. c. both the enzymes had no significant alteration over 70 hr value, beta-glucuronidase, however, did not show this type of pattern in all the segments till 144 hr p. c. The increased activity of acid RNase and DNase in AIJ and I segments of the tube till 70 hr p. c. suggests the increased lysosomal activity in the tubal fluid produced by secretory cells. The possible involvement of these lysomal factors in the process of fertilization and preparation of ovum prior to implantation is suggested.

Animals↗

Human tubal fluid: formation and composition during vascular perfusion of the fallopian tube.

A vascularly perfused preparation of the Fallopian tube has been developed as a model to study the formation and composition of human tubal fluid. An artery serving the tube was cannulated and perfused at a rate of 0.7 ml/min for 1 h with Medium 199 supplemented with bovine serum albumin, heparin and antibiotics. A cannula was also inserted into the lumen. Light and scanning electron micrographs of control and perfused tubes showed that the epithelial lining was intact after perfusion. Tubal fluid was collected in 13 out of 19 experiments. Fluid could always be collected from patients who were in the follicular phase of their ovarian cycle. The mean rate of appearance was 48 microliters/h. The glucose, lactate and pyruvate concentrations in the tubal fluid, as assessed by fluorescence microanalysis, were 0.53, 8.58 and 0.17 mM respectively. There were no correlations between metabolite concentration and the length of perfusion, cannulation time, patient's age or condition. This technique provides a controlled method with which to access and examine human tubal fluid and will allow the physiology of both healthy and diseased tubes to be studied.

Adult↗

Primary carcinoma of the Fallopian tube.

A series of 26 unreported cases of primary carcinoma of the Fallopian tube is presented. These cases were collected from seven hospitals in Portland, Oregon, for a period of 10 years, i.e., from 1963 to 1974. No statistical data can be made except to state that seven patients of the 26 are known to be alive and well. Of these seven living patients, two have been followed for over 5 years and five have been followed for over 2 years. All are free of disease at the present time. Three other patients lived over 5 years but finally died of their disease. All of these patients were in the Stage I category except two who were in the Stage II category. This suggests that any breakthrough of the serosa of the Fallopian tube is an ominous sign with poor prognosis. The need for earlier diagnosis and supplementary therapy for Stage II of this disease is discussed.

Aged↗

Carcinoma of the fallopian tube presenting as acute pelvic inflammatory disease.

BACKGROUND: Primary carcinomas of the fallopian tube are rare and their preoperative diagnosis is difficult due to the lack of specific symptoms. CASES: We present two tumors diagnosed in women 74 and 77 years old. On examination both patients presented as acute pelvic peritonitis with abdominal pain and tenderness with guarding and rebound, as well as fever and leukocytosis. At surgery, a left tubal carcinoma was found in each patient. Marked inflammatory and purulent reaction involving the uterus, the adnexa, and the pelvic peritoneum, and no abnormalities in the digestive tract were identified. A total hysterectomy with bilateral salpingo-oophorectomy was performed in both patients. CONCLUSION: Carcinoma of the fallopian tube should be considered in the differential diagnosis of pelvic peritonitis, a previously poorly reported clinical presentation.

Acute Disease↗

Fallopian tube malignancies: experience of Social Security Agency Aegean Maternity Hospital.

The aim of the study was to determine the clinical characteristics and management of fallopian tube malignancies together with the results there unto that had been diagnosed and treated in our oncology department retrospectively. Twelve cases of fallopian tube malignancies, of a total of 2155 gynecologic malignancies (0.55%), that had been diagnosed in or referred to our hospital between January 1986 and December 2001 were evaluated retrospectively. Eight of 12 cases were diagnosed after surgical intervention in our department. Staging laparotomies were applied to all of the eight cases. Complementary surgeries of other four cases who were referred to our department were done according to the same principles of cytoreductive surgery. Staging of the cases was done according to Federation of International Gynecologists and Obstetricians (FIGO). Adjuvant chemotherapy was applied to all of the cases except two (10 cases, 83.3%). Second-look laparotomy (SLL) was applied to two of the cases. Mean age of the cases was 54.2 (range 35-72) years. Histopathology of the cases was as follows: serous adenocarcinoma in 10 cases (83.3%), endometrioid adenocarcinoma in one case (8.3%), and undifferentiated carcinoma in one case (8.3%). Adjuvant chemotherapy (PAC regimen to eight of the cases and PP regimen to two cases) was applied to 10 of the cases (83.3%). SLL was applied to two cases. Another case had died because of local recurrence at the 27th month of the follow-up. Mean follow-up period of the cases was 37.8 months (range 1-144 months). Fallopian tube malignancies are very rare malignancies. Diagnosis can be made generally peri- or postoperatively. More extensive clinical research must be performed in order to have definite etiologic, diagnostic, management modalities, and prognostic markers.

Adenocarcinoma↗

Different roles of histamine receptor subtypes in ampullar & isthmic segments of human fallopian tube.

We have studied the influence of both menstrual cycle phase and subtype-selective histamine antagonists on the contractions produced by histamine isolated in human fallopian tubes. Histamine produced tonic contractions of the isolated preparations of both the ampullar and isthmic segments of the human fallopian tube were analyzed. The effects of both histamine and its antagonists were not dependent on the phase of the menstrual cycle. The isolated preparations of the ampullar segment from post menopausal patients were not responsive on histamine. When responding, the ampullar segments were slightly more sensitive to histamine than the isthmic segments. All three subtype selective histamine antagonists (pyrilamine, cimetidine and thioperamide) produced strong inhibition of histamine evoked contractions of the ampullar segment. On the other hand, only pyrilamine strongly inhibited histamine evoked contractions of the isthmic segment. The results of our study suggest that only H1 receptors were responsible for the histamine contractile effect on the isthmic segment and that all three subtypes of histamine receptors were involved in the effect of histamine on the ampullar segment of human fallopian tube.

Adult↗

Gemcitabine salvage chemotherapy for patients with gynecologic malignancies of the ovary, fallopian tube, and peritoneum.

The efficacy and toxicity of gemcitabine salvage chemotherapy was evaluated in 27 heavily pretreated patients with recurrent and progressive ovarian, fallopian tube, or peritoneal cancer. At least one platinum-based chemotherapeutic regimen had failed in each patient. The median number of previous chemotherapy regimens and cycles of chemotherapy was 4 and 23, respectively. A total of 124 cycles of gemcitabine were delivered (median, 3 cycles). Hematologic toxicity included four patients with grade 3/4 thrombocytopenia and two patients with grade 3/4 neutropenia. Thrombocytopenia and neutropenia resulted in eight dose reductions and a single 1-week treatment delay. Nonhematologic side effects were well tolerated and largely self-limiting. No complete responses were observed. Three patients (11%) demonstrated partial responses to therapy. The duration of response was 7 months for two of the responders and 5 months for the third responder. Stable disease was observed in 14 patients (52%), in whom the median progression-free interval was 5 months. In conclusion, among heavily pretreated patients, gemcitabine has limited antitumor activity in platinum-resistant carcinomas of the ovary, fallopian tube, and peritoneum. The role of gemcitabine in the treatment of gynecologic malignancies of the ovary, fallopian tube, and peritoneum will be determined by studies that define the efficacy of multiagent regimens of chemotherapy that include gemcitabine and by studies that include patients who have been less heavily pretreated.

Adult↗

A randomized, prospective, controlled study of laparoscopic dye studies and selective salpingography as diagnostic tests of fallopian tube patency.

OBJECTIVE: To determine and compare the relative merits of laparoscopic dye (LD) studies and selective salpingography (SS) as diagnostic tests of fallopian tube patency. DESIGN: Randomized, prospective, controlled study. SETTING: University-associated assisted reproduction unit. PATIENT(S): Two hundred seventy-eight women undergoing investigation of infertility. INTERVENTION(S): Allocation to the performance of either LD studies followed by SS or SS followed by LD studies conducted sequentially under general anesthesia. MAIN OUTCOME MEASURE(S): Detection of fallopian tube occlusion, including the site of obstruction and evidence of peritubal or pelvic disease. RESULT(S): When diagnosis was compared by the first test used, 16 (11.9%) of 135 patients had proximal tubal occlusion at LD studies versus 5 (3.6%) of 138 at SS. Twelve (5.6%) of 122 patients had distal tubal occlusion at LD studies versus 14 (10.5%) of 133 at SS. Fifteen (11.1%) of 135 patients had peritubal disease at LD studies versus 3 (2.52%) of 119 at SS. When diagnosis was compared by individual tubes, the results were similar. Among patients who had proximal occlusion and otherwise normal tubes by both methods, endometriosis was present in 72.2%. CONCLUSION(S): Selective salpingography is a better diagnostic test of proximal tubal occlusion than are LD studies. There is no difference between SS and LD studies as a diagnostic test of distal tubal occlusion. Laparoscopic dye studies are a better diagnostic test for assessing peritubal disease than is SS. There may be an association between endometriosis and proximal tubal occlusion. Selective salpingography and LD studies are complementary investigations of the fallopian tubes.

Adult↗

Possible involvement of ovarian mechanisms other than estrogen-progesterone secretion in the regulation of glutamic acid decarboxylase activity of the rat fallopian tubes.

This study was performed to clarify the physiological role of the ovary in regulating the glutamic acid decarboxylase (GAD) activity in rat Fallopian tubes. To this purpose, GAD activity of the oviduct was evaluated in the following experimental conditions: immature or adult castrated (CX) rats; immature or adult CX rats treated with graded doses of estradiol benzoate (EB) or a fixed dose of EB and progesterone; adult CX rats bearing Silastic implants able to produce steady state estradiol plasma levels in the range of diestrous values; and prepubertal rats treated with ovulatory or anovulatory doses of exogenous gonadotropins (PMS and hCG). Moreover, the possible fluctuations of both gamma-aminobutyric acid (GABA) concentrations and GAD activity in the Fallopian tubes were studied during the estrous cycle. The results show that the prepubertal rat oviduct possesses a GABA content and a GAD activity analogous to those of normal diestrous rats. The GAD activity measured with the CO2 formation method was well correlated with the formation of labeled GABA, indicating that tubes of prepubertal rats are able to form the neurotransmitter by means of specific decarboxylation of glutamate. GAD activity, but not GABA levels, was increased over control values by the administration of exogenous gonadotropins. The role of the ovary in both adult and prepubertal rats to regulate this enzymatic activity is further stressed by the results of the experiments performed in CX animals which showed that ovariectomy produced a 4- to 5-fold decrease in GAD activity independent of the age of the animals. However, implantation of Silastic estradiol-containing capsules in adult CX animals or the administration of EB for 5 days in a dose range from 0.001-6.4 micrograms/day to adult ovariectomized animals and from 0.001-0.2 microgram/day to prepubertal animals did not modify GAD activity in spite of marked peripheral estrogenization of the animals evidenced by increases in uterine weight. Moreover, no variation of the enzymatic activity was observed at puberty (assessed by the age at vaginal opening). The administration of progesterone (0.2 mg) plus EB (0.01 microgram) did not produce any significant variation in GAD activity. GABA content and GAD activity of the tubes did not change during the estrous cycle. We, therefore, believe that other ovarian, still unidentified, secretions might be involved in the regulation of GAD activity in rat Fallopian tubes.

Animals↗