J Med Primatol. 2010 Mar 15. [Epub ahead of print]Ovarian pathology in rhesus macaques: a 12-year retrospective.Marr-Belvin AK, Bailey CC, Knight HL, Klumpp SA, Westmoreland SV, Miller AD.Division of Comparative Medicine and Pathology, New England Primate Research Center, Harvard Medical School, Southborough, MA, USA.Abstract Background Ovarian pathology is an important ...
J Med Primatol. 2007 Dec;36(6):391-8
Endometriosis: clinical monitoring and treatment procedures in Rhesus Monkeys
Laboratory of Experimental Gerontology, NIA, NIH Animal Center, Poolesville, MD, USA. firstname.lastname@example.org
The National Institute on Aging (NIA) sponsored a workshop on September 8, 2004, to discuss the incidence, diagnosis, and clinical treatment of endometriosis in rhesus monkey colonies. Because of the growing number of aging studies using rhesus monkeys, this disease has become more prevalent as monkeys are living into advanced ages in captivity. The objective of the workshop was to gather information from various NIA-supported aging rhesus colonies on the incidence, clinical manifestations, indicators for early detection, and possible treatment options for endometriosis. Participants outlined a course of action for the effective management of this disease that would best maintain the integrity of long-term aging studies.
Akush Ginekol (Sofiia). 2007;46(4):38-47.
[Comparison and analysis of pain profiles in women with endometriosis and pelvic congestion syndrome–part II][Article in Bulgarian]
PURPOSE OF THE STUDY: To compare and analyze the pain profiles of patients with endometriosis /E/, adenomyosis /A/, and pelvic congestion syndrome /PCS/ in order to specify the factors that make closer the profiles of these conditions, and the factors, that make the differences between them clearer. MATERIALS AND METHODS: A prospective study was conducted in the Clinic of Gynaecology, Department of Obstetrics and Gynaecology, Medical University-Pleven in the period 01.03.2004-01.02.2006. It included 98 patients consequently admitted in the Clinic–66 patients suspected of or with proven E, and 32 patients with PCS. For the purpose of the study the following methods were used: pain chart, visual-analogue scale /VAS/, monthly pain calendar, documentary method, R-AFS classification of endometriosis and inquiry method. RESULTS AND DISCUSSION: The object of interest in this study were the pain profiles of E, A and PCS, and the dependence and association of severity of manifestation of the particular components of the pelvic pain syndrome /dysmenorrhoea, dyspareunia, postcoital ache, etc./ of the conditions mentioned above, on: stage of endometriosis, localization of endometriotic foci, diameter of maximal dilation and location of varicosely altered pelvic veins in women with PCS. It was found that the intensity and specificity of component demonstration of pelvic pain syndrome of women with endometriosis were not dependent on the stage of the disease, but on location of endometriotic lesions. In patients with PCS the severity and specific character of chronic pain syndrome were dependent on diameter of maximal dilation and site of varicose pelvic veins. According to its characteristics, pain profile of women A takes a specific place between the peculiar profiles of patients with E and PCS.
Akush Ginekol (Sofiia). 2007;46(5):37-48.
[Endometriosis and the role of the integrins in the pathogenesis of the endometriosis]
The endometriosis is gynecological disease what is characterized with the presence of endometrial lesions are composed of endometrial epithelial and stromal cells outside of the uterus. There are many theories for the development of the disease endometriosis. The most widely accepted theory is the theory what is postulated the endometriosis is a result of retrograde menstruation. The essential stage in the 00141process of development of endometrial lesions is the process of adhesion of endometrial cells on the peritoneal surface and on the organs, are situated in the peritoneal cavity. The adhesion molecules (integrins) have the most essential role in this first stage. The integrins are cell surface receptors with glycoprotein structure. They have part in process of adhesion of the endometrial cells to the proteins from EC matrix outside the uterus. The integrins have part like signal molecules in the processes of proliferation and invasion of endometrial implants. They are very essential molecules what influence the viability of endometrial implants as well as the angiogenesis in the new forming endometrial implants. Improvement of the studies, related to the roles of the integrins in the pathogenesis of endometriosis would be give new possibilities to search more effective methods for therapy of the endometriosis.
Expert Opin Investig Drugs. 2007 Nov;16(11):1851-63.
Leuprolide acetate: a drug of diverse clinical applications.
University of Wisconsin-Madison, Department of Medicine, and Geriatric Research, Education and Clinical Center, William S Middleton Memorial Veterans Administration Hospital, 2500 Overlook Terrace, Madison, WI 53705, USA. email@example.com
Leuprolide acetate is a synthetic nonapeptide that is a potent gonadotropin-releasing hormone receptor (GnRHR) agonist used for diverse clinical applications, including the treatment of prostate cancer, endometriosis, uterine fibroids, central precocious puberty and in vitro fertilization techniques. As its basic mechanism of action, leuprolide acetate suppresses gonadotrope secretion of luteinizing hormone and follicle-stimulating hormone that subsequently suppresses gonadal sex steroid production. In addition, leuprolide acetate is presently being tested for the treatment of Alzheimer’s disease, polycystic ovary syndrome, functional bowel disease, short stature, premenstrual syndrome and even as an alternative for contraception. Mounting evidence suggests that GnRH agonist suppression of serum gonadotropins may also be important in many of the clinical applications described above. Moreover, the presence of GnRHR in a multitude of non-reproductive tissues including the recent discovery of GnRHR expression in the hippocampi and cortex of the human brain indicates that GnRH analogs such as leuprolide acetate may also act directly via tissue GnRHRs to modulate (brain) function. Thus, the molecular mechanisms underlying the therapeutic effect of GnRH analogs in the treatment of these diseases may be more complex than originally thought. These observations also suggest that the potential uses of GnRH analogs in the modulation of GnRH signaling and treatment of disease has yet to be fully realized.
Acta Neurol Taiwan. 2007 Sep;16(3):173-6.
Intracranial hypertension associated with danazol withdrawal: a case report.
Department of Neurology, Chang-Gung Memorial Hospital Kaohsiung Medical Center, Chang-Gung University College of Medicine, Niaosung, Kaohsiung, Taiwan.
Pseudotumor cerebri (PTC) is a seldom seen entity characterized by signs and symptoms associated with the intracranial hypertension (IH) without obvious causes. Some medical disorders and exogenous agents have been implicated in the development of PTC. Danazol is a popular gonadotropin inhibitor used for the treatment of endometriosis, breast disease and hereditary angioedema. While PTC has been occasionally reported in patients receiving danazol treatment, it is barely mentioned in those who discontinued danazol therapy abruptly. Here we report a case of IH developed soon after the withdrawal of danazol.
Chirurgia (Bucur). 2007 Jul-Aug;102(4):421-8.
[Laparoscopic surgery of profund endometriosis with rectal affect][Article in Romanian]
Clinica Ginecologie şi Obstetrică, Spitalul Universitar Rouen, Franta. Horace.Roman@chu-rouen.fr
OBJECTIVE: To present the principles of laparoscopic treatment for rectal endometriosis and to discuss possible postoperative outcomes. MATERIAL AND METHODS: Our series included women managed for rectal endometriosis during consecutive 20 months in the Department of Gynecology and Obstetrics, Rouen University Hospital, Rouen–France. Patient’s characteristics, symptoms, imaging examination results, surgical treatment and postoperative outcomes were all evaluated retrospectively. RESULTS: Sixteen patients presenting with rectal endometriosis were managed surgically, (mean age was 35.9 +/- 6.5 years). All women presented at least one severe painful symptom which was typical of a digestive involvement in 12 cases. MRI results suggested a rectal involvement in 14 cases, and endorectal ultrasound examination clearly showed rectal wall infiltration in all patients. The gynaecological stage of surgical treatment was carried out laparoscopically in 13 cases, and the digestive surgical stage in 7 cases. Two limited and 14 segmental rectal resections were performed. Transitory stoma was carried out in 9 women. The length of the surgical procedure depended on the number of endometriosis localizations with a median value of 6 h 30 min. Postoperative complications occurred in 6 women: 2 anastomosis stenosis, 1 anastomosis fistula, 1 abscess of the parietal wall and 1 bladder atonia. Complains of pain were completely or significantly improved in all cases. CONCLUSION: Surgical treatment for rectal endometriosis may be carried out laparoscopically. It should be reserved for women presenting with severe painful condition and may contribute to significant improvement. However, the balance of benefit and risks must also be assessed on a case to case basis prior to any decision for or against surgical treatment.
Eur J Gynaecol Oncol. 2007;28(5):403-5.
Ovarian clear cell carcinoma associated with endometriosis: a case report with immunohistochemical study.
Research Institute of Oncology (IPON), Discipline of Gynecology and Obstetrics, Federal University of Triângulo Mineiro (UFTM), Uberaba-MG, Brazil.
Endometriosis is a frequent benign gynecological disease; nonetheless, it can demonstrate some aspects that resemble malignant disease. Malignant transformation of endometriosis occurs mainly in the ovary. A rare case of transition between typical endometriosis and clear cell carcinoma with immunohistochemical study is presented. The patient, a 30-year-old Caucasian woman (para 0), was diagnosed with endometriosis ten years before. Six months later she developed a left cystic ovarian tumor (58 cm3) that persisted after two ultrasounds in a four-month period. Tumor markers were normal (CA125, CA 15.3, CA 19.9, alpha-fetoprotein, carcinoembrionary antigen A1). There was no ascites. The left ovarian mass was removed by laparotomy and endometriosis in continuity with carcinoma positive for cytokeratin 7 and estrogen receptor was revealed. CD10 was positive in the stromal cells of the endometriosis. Clear cell carcinoma grade 3 was diagnosed. In conclusion, although a rare event, the association of typical endometriosis and clear cell carcinoma of the ovary should be kept in mind, mainly in patients with a persistent ovarian cyst.
Acta Obstet Gynecol Scand. 2007;86(11):1352-8.
Vascular endothelial growth factor +936 C/T polymorphism is associated with an increased risk of endometriosis in a Japanese population.
Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan.
BACKGROUND: Vascular endothelial growth factor (VEGF) concentration in endometriosis patients is higher than controls, in serum and ascites, suggesting that VEGF may play an important role in the pathogenesis of endometriosis. In this study, we investigated whether polymorphisms in the VEGF gene are associated with endometriosis in a Japanese population. METHODS: Genotyping of VEGF -460 C/T, +405 G/C and +936 C/T polymorphisms were performed in 147 endometriosis cases diagnosed by laparotomy or laparoscopy at a university hospital, and 181 controls, by polymerase chain reaction-restriction fragment length polymorphism analysis. We compared the genotype distribution and allele frequency of these 3 polymorphisms between endometriosis patients and controls. RESULTS: No significant differences in the frequency and genotype distribution of VEGF -460 C/T, +405 G/C and +936 C/T polymorphisms were found between the endometriosis patients (all disease stages) and controls. However, a positive association was found between stage III-IV disease and the VEGF +936 T allele (p=0.018). CONCLUSIONS: The VEGF +936 T allele is associated with an increased risk of stage III-IV endometriosis in a Japanese population.
Semin Reprod Med. 2007 Nov;25(6):461-75.
Uterine receptivity: alterations associated with benign gynecological disease.
Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, Virginia 23507, USA.
The role of the endometrium is to establish and maintain pregnancy. Endometrial receptivity is established during the mid-secretory phase, between cycle day (CD) 20 to 24, or 6 to 10 days after ovulation. In some cases of infertility or recurrent pregnancy loss, implantation failure is due to a lack of expression of specific critical participating proteins such as cell adhesion molecules. Numerous cell adhesion molecules (including integrins, selectins, and cadherins) are expressed by the endometrium and appear to be necessary for the successful interaction of the embryo with the endometrium. One of the best-characterized cell adhesion molecules are the integrins. Integrins are transmembrane glycoproteins that belong to a large family comprising alpha and beta subunits, and are present on virtually all cells in the body. Women with various benign gynecologic disorders, including endometriosis, polycystic ovarian syndrome, hydrosalpinges, and luteal phase defect, appear to exhibit decreased uterine receptivity and abnormal expression of endometrial biomarkers. This review addresses proposed mechanisms of implantation and endocrine and paracrine signals responsible for the establishment of endometrial receptivity as well has the possible mechanisms of dysfunction in certain types of infertility in women with benign gynecologic disease.
Semin Reprod Med. 2007 Nov;25(6):431-6.
HOX genes in implantation.
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Implantation is a complex event requiring synchronization between a developing embryo and receptive endometrium. This process is governed by molecular mechanism mediated by homeobox (Hox) genes, which encode transcription factors. These factors guide embryologic development as well as regulate differential gene expression within the endometrium with each menstrual cycle. Spatiotemporal aberrations in HOX gene expression as seen with polycystic ovarian syndrome, endometriosis, hydrosalpinges, and endocrine disrupters compromise implantation. The role of HOX genes and their products continues to be explored as animal models that demonstrate implantation-specific infertile phenotypes continue to be investigated.
Reprod Sci. 2007 Sep;14(6):595-604.
Endometriosis markers: immunologic alterations as diagnostic indicators for endometriosis.
Department of Obstetrics, Gynecology and Women’s Health, University of Louisville School of Medicine, Louisville, Kentucky, USA.
Because endometriosis, a chronic disease affecting 7% to 10% of women, is associated with immunologic aberrations, the authors hypothesize that the presence of specific immune alterations may be diagnostic. Autoantibodies were assayed by Western immunoblotting using antigens derived from the plasma membrane, cytosol, and nucleus from endometrial and ovarian cells. Natural killer (NK) activity was defined by levels of signaling protein zeta and induction of interferon (IFN)-gamma following exposure to patients’ sera. Patients with endometriosis exhibited autoantibodies reactive with cellular proteins; endometrial membrane proteins exhibited the greatest reactivity, followed by nuclear antigens. In all subcellular fractions, patients with stage 3 endometriosis exhibited significantly more immunoreactivity than did stage 2 patients, which was greater than that observed in stage 1 patients. The stage-associated increased reactivity resulted from both recognition of additional proteins and enhanced reactivity with shared proteins. Patient sera suppressed NK zeta expression, which resulted in suppression of NK IFN induction. Alterations in autoreactivity and NK activity are observed in endometriosis and may be useful as diagnostic markers, even in early stage disease.
Pain. 2007 Nov;132 Suppl 1:S150-9. Epub 2007 Oct 23.
Endometriosis-induced vaginal hyperalgesia in the rat: effect of estropause, ovariectomy, and estradiol replacement.
Program in Neuroscience, Eppes Hall, Copeland Street, Florida State University, Tallahassee, FL 32306-1270, USA. firstname.lastname@example.org
Endometriosis (ENDO) is a painful disorder defined by extrauteral endometrial growths. It is created in rats by autotransplanting pieces of uterus (which form cysts), or, for shamENDO, fat (no cysts). ENDO induces vaginal hyperalgesia, likely via central sensitization. The severity of this hyperalgesia correlates with estradiol levels during the estrous cycle, suggesting the hyperalgesia is estradiol-modulated. If so, then hyperalgesic severity should track estradiol changes during reproductive senescence (estropause) when estradiol levels initially decrease, then increase. Using psychophysical methods to assess vaginal nociception, we found that the severity of ENDO-induced hyperalgesia paralleled estradiol changes during estropause: hyperalgesia first decreased, then returned. Furthermore, the return occurred regardless of the presence of the cysts (excised in some rats). This finding provides further support for ENDO’s likely centrally-mediated effects. Additionally, the results suggest that elimination of estradiol via ovariectomy (OVX) should alleviate ENDO-induced hyperalgesia and estradiol replacement should restore it. However, in healthy and shamENDO rats, OVX produces a vaginal hyperalgesia that is alleviated by estradiol, likely via estradiol’s peripheral influences on the vagina. Hence, we tested the hypothesis that OVX in ENDO rats would trigger a different type of vaginal hyperalgesia dependent on the loss of estradiol. We predicted that the opposing influences of estradiol on ENDO- and OVX-induced hyperalgesia would cancel each other. As predicted, OVX had no effect on ENDO-induced hyperalgesia and estradiol replacement alleviated it. These results suggest that, in intact rats, ENDO-induced vaginal hyperalgesia is exacerbated by estradiol, and that different mechanisms underlie ENDO-induced versus OVX-induced vaginal hyperalgesia.
J Med Assoc Thai. 2007 Sep;90(9):1934-6.
Laparoscopic nephrectomy, hysterectomy and rectovaginal endometriotic mass removal in a single session.
Section of Minimally Invasive Surgery, Division of Urology, Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama 6 Rd, Tungphyatai, Rajathevee, Bangkok 10400, Thailand. email@example.com
The authors reported the first case of endometriosis with ureteral involvement causing nonfunctioning kidney, which was managed by laparoscopic nephrectomy, hysterectomy, and endometriotic mass removal in a single session.
Hum Reprod. 2007 Dec;22(12):3159-69. Epub 2007 Oct 23.
Differentially expressed genes in human endometrial endothelial cells derived from eutopic endometrium of patients with endometriosis compared with those from patients without endometriosis.
Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Peking, People’s Republic of China.
BACKGROUND: The pathogenesis of endometriosis remains poorly defined. The aberrant angiogenesis that occurs in eutopic endometrium may play a role in the lesion formation and survival. The difference in gene expression profile between human endometrial endothelial cells (HEECs) from eutopic endometria of patients with and without endometriosis would be a factor that affects the occurrence of endometriosis. METHODS: To explore the difference, we performed in vitro culture and identified the endothelial origin, as well as observed growth features, of HEECs from the two different sources. We also identified their differences in gene expression profiles by combined suppression subtractive hybridization (SSH) with Genechip, and confirmed the results by quantitative reverse transcription-polymerase chain reaction. RESULTS: The HEECs derived from endometriosis patients exhibited a potent survival ability in vitro compared with those from non-endometriosis patients. In the HEECs from EM patients, an altered secretion pattern of extracellular matrix (ECM) components and up-regulation of GREM1 were found. These findings may be used to interpret the remarkable change of phenotype in HEECs from endometriosis patients. The synergistic action of these differentially expressed genes is to promote cell proliferation and concomitantly to inhibit apoptosis. Among the up-regulated ECM genes, TSP2 was the only one which exhibits the capacity to suppress angiogenesis; it may therefore function as an antagonist to the aberrant angiogenesis and may confine its extent and severity. CONCLUSION: It may be postulated that differential regulation of some of these genes in eutopic HEECs plays a facilitating role during the peritoneal vascularization of ectopic endometrial lesions by enhancing angiogenic activity via a paracrine effect.
Hum Reprod. 2007 Dec;22(12):3232-6. Epub 2007 Oct 23.
Intrauterine exposures and risk of endometriosis.
Department of Health and Human Services, Epidemiology Branch, National Institute of Child Health & Human Development, Rockville, Maryland 20852, USA. firstname.lastname@example.org
BACKGROUND: Intrauterine environmental exposures have been adversely associated with male reproductive health in contrast to limited investigation of such exposures and female reproductive health. METHODS: To address this research gap, a cohort comprising 84 women aged 18-40 years undergoing laparoscopy was recruited prior to surgery and followed through the post-operative period for endometriosis diagnosis. Women were interviewed about environmental exposures and those of their mothers while pregnant with them (use of alcohol, caffeinated beverages and cigarettes). Endometriosis was diagnosed in 32 women from the laparoscopy cohort; 52 women had no endometriosis visualized. Using unconditional logistic regression, odds ratios (OR) and 95% confidence intervals (CIs) were estimated for the intrauterine exposures adjusting for potential confounders. RESULTS: No significant associations were seen between intrauterine exposure to alcohol or caffeine and a diagnosis of endometriosis. Adjusting for age, significant reductions in odds of an endometriosis diagnosis were observed for intrauterine cigarette exposure both in the absence (OR 0.22, 95% CI 0.06-0.82) or presence (OR 0.05, 95% CI 0.01-0.42) of women’s current smoking. CONCLUSIONS: While speculative, in utero cigarette exposure may be associated with a lower risk of surgically diagnosed adult-onset endometriosis, possibly as a result of alterations in hormonal milieu or pathologic angiogensis.
Arch Intern Med. 2007 Oct 22;167(19):2061-5.
Personal history of endometriosis and risk of cutaneous melanoma in a large prospective cohort of French women.
Institut National de la Santé et de la Recherche Médicale, ERI 20, Institut Gustave Roussy, 39 rue Camille Desmoulins, F94805 Villejuif CEDEX, France.
BACKGROUND: An association between melanoma and endometriosis has been reported, but most findings relied on case-control studies or a limited number of melanoma cases, and therefore the available evidence is weak. Moreover, the effect of other benign gynecological diseases on melanoma risk is unknown. METHODS: We prospectively studied data from the Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l’Education Nationale cohort, which includes 98 995 French women, insured by a national health scheme mostly covering teachers, aged 40 to 65 years at inclusion. Data on history of endometriosis and other benign gynecological diseases were regularly collected, starting in 1990. Relative risks and 95% confidence intervals were computed using Cox proportional hazards regression models. RESULTS: During 12 years of follow-up, 363 melanoma cases were ascertained among 91 965 subjects. A history of endometriosis (n = 5949) was significantly associated with a higher risk of melanoma (relative risk, 1.62; 95% confidence interval, 1.15-2.29). There was also a significantly increased risk among women with a history of fibroma (n = 24 375), compared with those who had no such history (relative risk, 1.33; 95% confidence interval, 1.06-1.67). A history of ovarian cyst, uterine polyp, breast adenoma/fibroadenoma, or breast fibrocystic disease was not significantly associated with risk. CONCLUSIONS: These data provide the strongest evidence to date of a positive association between a history of endometriosis and melanoma risk. The association between fibroma and melanoma, which has not been previously described, warrants further investigation.
Gynecol Endocrinol. 2007 Oct;23(10):574-80.
Paracrine regulation of endometriotic tissue.
Cattedra di Fisiopatologia della Riproduzione Umana, Università Cattolica del Sacro Cuore, Rome, Italy. email@example.com
Endometriosis is a chronic estrogen-dependent gynecological disease, characterized by pelvic pain and infertility, defined as the presence of endometrial glands and stroma within the pelvic peritoneum and other extrauterine sites. In the peritoneal cavity endometrial cells adhere, proliferate and induce an inflammatory response. Despite a long history of clinical and experimental research, the pathogenesis of endometriosis is still controversial. Abnormal immunological activation, the endocrine milieu and the peritoneal environment all dramatically affect endometriotic tissue function. Recent studies suggest that the peritoneal fluid of women with endometriosis contains an increased number of activated macrophages and other immune cells that secrete various local products, such as growth factors and cytokines, which exert a paracrine action on endometriotic cells. Since the peculiar biological characteristics of eutopic endometrium from women with endometriosis differ from endometrium of normal subjects, an important role in the pathogenesis of this complex disease has been suggested. All of these factors contribute to enhanced proliferative and angiogenic activity and a number of functional and structural changes, resulting in the particular behavior of this tissue.
Gynecol Endocrinol. 2007 Oct;23(10):567-73.
Expression of membrane-type 5 matrix metalloproteinase in human endometrium and endometriosis.
Department of Obstetrics and Gynecology, Johann Wolfgang Goethe-University, Frankfurt, Germany. firstname.lastname@example.org
BACKGROUND: The metalloproteinases (MMPs) are a family of proteolytic enzymes involved in tissue remodeling and cell migration. Endometrial tissue remodeling proceeds during the menstrual cycle and requires a temporary and spatially balanced expression of several different MMPs. Various members of the MMPs also seem to play an important role in the invasion process of endometriosis; however, so far only a limited number of studies have focused on membrane-associated MMPs. METHODS: The present study investigated the expression of membrane-type 5 metalloproteinase (MT5-MMP) in the human endometrium and endometriotic lesions by microarray hybridization, real-time polymerase chain reaction (PCR) and immunofluorescence. RESULTS: Both the gene chip expression analyses as well as PCR indicated expression of MT5-MMP in normal human endometrium and strongly elevated transcript levels in most peritoneal endometriosis lesions analyzed. Moreover we detected enhanced MT5-MMP expression in the eutopic endometrium from patients suffering from endometriosis, further supporting a role of MT5-MMP in the formation of endometriosis. Immunohistochemical analysis was used to determine the intracellular localization and tissue distribution of MT5-MMP. While the MT5-MMP antigen expression could be clearly attributed to the membrane of epithelial cells, a highly complex differential immunohistochemical staining of MT5-MMP in the various compartments of endometrial tissue was observed. The strongest staining was seen in luminal epithelial cells, whereas endometrial glands frequently showed partial expression of MT5-MMP. CONCLUSION: Our microarray analysis and real-time PCR of MT5-MMP transcripts may point to an elevated tissue remodeling and cell migration in endometrium from endometriosis patients as implied by the function of related MMPs.
Rev Assoc Med Bras. 2007 Sep-Oct;53(5):433-8.
[Evaluation of pain and depression in women with endometriosis after a multi- professional group intervention][Article in Portuguese]
Ambulatório de Endometriose, Centro de Atenção Integral a Saúde da Mulher, Universidade Estadual de Campinas, Campinas, SP, Brasil.
OBJECTIVE: Evaluate pain and depression scores before and after multi-professional group intervention in women with endometriosis as compared to those who did not participate in this activity. METHODS: A total of 128 women attended at the Endometriosis Outpatient Facility CAISM/UNICAMP, was assessed and distributed equally into two groups: women who received group intervention and those who did not. All women completed the Beck Depression Inventory and the Analogical Visual Scale. RESULTS: There was a significant decrease in pain and depression scores at the end of group intervention. Women who had not participated in the intervention had higher initial scores of pain when compared to those who had. On the other hand, in the group without intervention,depression scores were lower. A positive correlation was identified between pain and depression in both groups. CONCLUSION: Group intervention was efficient in diminishing pain and depression in women with endometriosis and may be included in the conventional treatment for patients affected by this disease.
Gynecol Obstet Fertil. 2007 Nov;35(11):1155-65. Epub 2007 Oct 22.
[The place of photodynamic therapy in gynecology][Article in French]
Clinique de Gynécologie, Obstétrique et Néonatalogie, Hôpital Jeanne-de-Flandre, CHRU de Lille, Lille Cedex, France.
Photodynamic therapy (PDT) is a specific anticancer treatment that received significant interest in several medical and surgical disciplines. The technique is based on (i) the application of the photosensitizer that accumulates in a variable time in the neoplasic lesions and on (ii) excitation (by light whose wavelength coincides with the absorption peak of the photosensitizer) that (iii) finally causes the destruction of the lesion. This technique allows a minimally-invasive, effective and targeted treatment of some gynecological diseases. Experimental and/or clinical studies have been conducted on vulvar intraepithelial neoplasia, cervical intraepithelial neoplasia, ovarian cancer, breast cancer, dysfunctional uterine bleeding, endometriosis and vulvar lichen sclerosus. We aim to present the principles of PDT and to expose the main indications and ways of research of this technique in gynecology today.
Ther Umsch. 2007 Jul;64(7):349-52.
[Endometriosis][Article in German]
Klinik für Gynäkologie und Geburtshilfe, Universitätsklinikum Schleswig-Holstein, Campus Kiel. email@example.com
The major symptom is dysmenorrhea. Chronic, sometimes non-cyclic pain due to pelvic adhesions is often seen in the long course of the disease. Infiltration into the blader or bowel is a rare but serious complication. A group of patients presents with sterility. Endometriosis histologically resembles endometrium. There can be ovarian cysts and foci either on the peritoneum or in the muscularis of the uterus. The etiology is unknown. There are a number of existing theories. A rare condition is an endometriosis caused iatrogen during a caesarean section. It can develop between uterus and bladder or within the suture or scar tissue. Since we know so little, the treatment options are unsatisfying. Operative resection followed by endocrine medication is the standard therapy. Alternative medicine can be an useful additional factor in the treatment concept.
Tidsskr Nor Laegeforen. 2007 Oct 4;127(19):2528-9.
[A pregnant woman with abdominal pain and fever][Article in Norwegian]
Kirurgisk avdeling, Rikshospitalet-Radiumhospitalet, 0027 Oslo. firstname.lastname@example.org
Ectopic deciduosis is most often located in the ovaries, cervix and uterus, but can also be located on peritoneal surfaces of pelvic- and abdominal organs. The findings from surgical biopsies taken during pregnancy are mostly asymptomatic and incidental. Deciduosis of the appendix is rare, but it is a known differential diagnosis to acute appendicitis in pregnancy. We report a 27-year-old woman, Gravida 1, Para 0 in gestational week 35, who presented with acute right abdominal pain. She underwent an acute caesarean section for possible abruptio placentae. Acute appendicitis was a differential diagnosis. Peroperative findings revealed an inflamed and enlarged appendix suspicious for tumour. A pathological examination of the appendix showed decidual changes through the entire wall without signs of appendiceal endometriosis. In conclusion, symptomatic ectopic deciduosis in pregnancy is rare and may imitate acute appendicitis. This is an important differential diagnosis in pregnant women with tumour-suspect findings.
Hum Reprod. 2007 Dec;22(12):3092-7. Epub 2007 Oct 18.
Comparison between clinical examination, transvaginal sonography and magnetic resonance imaging for the diagnosis of deep endometriosis.
Department of Obstetrics and Gynecology, São Paulo University, 550 Rua São Sebastião, 04708-001 São Paulo, Brazil. email@example.com
BACKGROUND: Deeply infiltrating endometriosis affecting the retrocervical region and the rectosigmoid generally requires surgical treatment. Clinical examination, transvaginal ultrasonography (TVUS) and pelvic magnetic resonance imaging (MRI) are useful in the preoperative diagnosis of the involvement of these sites. The objective of this study was to evaluate the capacity of digital vaginal examination, TVUS and MRI to diagnose rectosigmoid and retrocervical involvement. METHODS: A total of 104 patients with clinically suspected endometriosis were submitted to clinical examination, pelvic MRI and TVUS until 3 months prior to videolaparoscopy and the findings of these methods were matched with histopathological confirmation of endometriosis. RESULTS: Endometriosis was histologically confirmed in 98 of 104 (94.2%) patients. With respect to the rectosigmoid and retrocervical sites, respectively, digital vaginal examination had a sensitivity of 72 and 68%, specificity of 54 and 46%, positive predictive value (PPV) of 63 and 45%, negative predictive value (NPV) of 64 and 69% and accuracy of 63 and 55%. For TVUS, sensitivity was 98 and 95%, specificity 100 and 98%, PPV 100 and 98%, NPV 98 and 97% and accuracy 99 and 97%. MRI had a sensitivity of 83 and 76%, specificity of 98 and 68%, PPV of 98 and 61%, NPV of 85 and 81% and accuracy of 90 and 71%. CONCULSIONS: TVUS had better sensitivity, specificity, PPV, NPV and accuracy in cases of deep retrocervical and rectosigmoid endometriosis when compared with MRI and digital vaginal examination, confirming that it is an important preoperative examination for the definition of surgical strategies.
Cochrane Database Syst Rev. 2007 Oct 17;(4):CD000068.
Danazol for pelvic pain associated with endometriosis.
BACKGROUND: Endometriosis is defined as the presence of endometrial tissue (stromal and glandular) outside the normal uterine cavity. Conventional medical and surgical treatments for endometriosis aim to remove or decrease the deposits of ectopic endometrium. The observation that hyper androgenic states (an excess of male hormone) induce atrophy of the endometrium has led to the use of androgens in the treatment of endometriosis. Danazol is one of these treatments. The efficacy of danazol is based on its ability to produce a high androgen and low oestrogen environment (a pseudo menopause) which results in atrophy of the endometriotic implants and thus an improvement in painful symptoms. OBJECTIVES: To determine the effectiveness of danazol compared to placebo or no treatment in the treatment of the symptoms and signs, other than infertility, of endometriosis in women of reproductive age. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register of trials (searched April 2007), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2007), and MEDLINE (1966 to April 2007). In addition, all reference lists of included trials were searched, and relevant drug companies were contacted for details of unpublished trials. SELECTION CRITERIA: Randomised controlled trials in which danazol (alone or as adjunctive therapy) was compared to placebo or no therapy. Trials which only reported infertility outcomes were excluded. DATA COLLECTION AND ANALYSIS: Only five trials met the inclusion criteria and two authors independently extracted data from these trials. All trials compared danazol to placebo. Three trials used danazol as sole therapy and three trials used danazol as an adjunct to surgery. Although the main outcome was pain improvement other data relating to laparoscopic scores and hormonal parameters were also collected. MAIN RESULTS: Treatment with danazol (including adjunctive to surgical therapy) was effective in relieving painful symptoms related to endometriosis when compared to placebo. Laparoscopic scores were improved with danazol treatment (including as adjunctive therapy) when compared with either placebo or no treatment. Side effects were more commonly reported in those patients receiving danazol than for placebo. AUTHORS’ CONCLUSIONS: Danazol is effective in treating the symptoms and signs of endometriosis. However, its use is limited by the occurrence of androgenic side effects.
J Reprod Med. 2007 Sep;52(9):805-9.
Outcome of in vitro fertilization and ovarian response after endometrioma stripping at laparoscopy and laparotomy.
Department of Obstetrics and Gynecology, Gulhane Military Medical Academy (GATA) School of Medicine, Ankara, Turkey. firstname.lastname@example.org
OBJECTIVE: To add further data on in vitro fertilization (IVF) outcome and ovarian response after endometrioma stripping via either laparoscopy or laparotomy. STUDY DESIGN: IVF outcome and ovarian response parameters in patients who had undergone unilateral endometrioma stripping at laparoscopy (n=28) or laparotomy (n=10) before IVF were retrospectively compared. RESULTS: Fertilization rates, number of embryos transferred and pregnancy rates did not differ between the groups. Significantly more recombinant FSH was used to induce folliculogenesis, and fewer metaphase II oocytes were retrieved in the laparotomy group. The laparotomy-postcystectomy ovaries were significantly smaller and malpositioned. In both stripping groups, significantly smaller operated-on ovaries with lower numbers of antral and mature follicles were observed as compared to intact ovaries. CONCLUSION: A higher amount of FSH is needed to achieve an acceptable IVF outcome after unilateral endometrioma surgery. Indications for surgical treatment of patients having larger and bilateral cysts with an expectation for future fertility should be cautiously reviewed
Clin Exp Obstet Gynecol. 2007;34(3):179-81.
Long-term personalized GnRH agonist therapy without estrogen supplementation for recurrent endometriotic catamenial pneumothorax–case report.
Department of Obstetrics and Gynecology, Wakayama Medical University Wakayama, Japan.
A patient with diaphragmatic endometriosis who showed immediate relapse following radical thoracoscopic surgery received personalized GnRH agonist (GnRHa) therapy. GnRHa depots were subcutaneously injected by modulating injection intervals according to serum estradiol and LH levels in order to maintain long-term amenorrhea without any adverse effects. A leuprolide acetate depot was injected 24 times for 34 months. Therefore, so far, 1.88 mg of leuprolide acetate depot have been injected every seven weeks to achieve a stable endocrine condition with 15-30 pg/ml serum estradiol, 3-10 IU/l serum LH, and 7-15 IU/lI serum FSH.
Clin Exp Obstet Gynecol. 2007;34(3):168-70.
Contribution of laparoscopy in young women with abdominal pain.
Department of Obstetrics and Gynecology Institute, Aschaffenburg, Germany.
This study retrospectively evaluates the laparoscopic treatment of acute abdominal pain in 120 young girls aged 13 to 25 years from 1990 to 1995. Seventy-two (60%) of all operations were emergency procedures. Of these, 55 had functional ovarian cysts, eight patients were operated on for adnexal torsion and nine patients had other adnexal conditions. Ovarian cyst resection was performed in 46 patients and ovarian cyst coagulation in 17 patients. In the rest of the 48 patients (40%), 31 (26.67%) cases had pelvic inflammatory disease, three (2.5%) benign ovarian tumors, two (1.6%) ectopic pregnancies, one (0.8%) a paraovarian cyst and 11 (5%) endometriosis. Laparoscopy appeared to be a safe and effective surgical procedure.
Clin Exp Obstet Gynecol. 2007;34(3):163-7.
Adenomyosis: prevalence, risk factors, symptoms and clinical findings.
Department of Obstetrics and Gynecology, Ege University Faculty of Medicine, Izmir, Turkey.
OBJECTIVE: This prospective study investigated the prevalence of adenomyosis in histopathological examinations of patients who had undergone hysterectomy due to various indications in our clinic. Epidemiological characteristics, predisposing risk factors, symptoms and clinical findings of adenomyosis were evaluated. METHOD: A total of 298 subjects who had undergone abdominal, vaginal or laparoscopic hysterectomy with/without salpingooophorectomy between October 2003 and April 2004 in our clinic were included. Uterine specimens obtained through hysterectomy were weighed and histopathologically examined in the Pathology Department of Ege University. The study group (n = 103), cases with adenomyosis, was compared with the control group (n=195), cases without adenomyosis, with respect to the epidemiological, clinical and histopathological characteristics. RESULTS: The prevalence of adenomyosis in 298 subjects was 36.2% (103). Duration of the reproductive period in patients with adenomyosis was found to be significantly longer than for those in the control group (p < 0.05). Prevalence of pelvic pain, dysmenorrhea and dyspareunia was also significantly higher in the study group (p < 0.05). Moreover, the number of cases requiring blood transfusion before the operation was significantly higher in the study group (p < 0.05) as were the rates of smoking, previous uterine surgery and nulliparity (p < 0.05). The most common gynecological condition accompanying adenomyosis was found to be uterine myoma in both groups, but the difference was not significant. CONCLUSION: Adenomyosis is not a rare histopathological finding. Due to diagnostic and therapeutic methods which are being developed as an alternative to hysterectomy, the clinical effects of adenomyosis and its association with other gynecological conditions, adenomyosis appears to be an issue which will be more intensively investigated in the future.
Gynecol Obstet Invest. 2007;64(3):149-55. Epub 2007 Oct 4.
The baboon as a research model for the study of endometrial biology, uterine receptivity and embryo implantation.
Leuven University Fertility Center, Department of Obstetrics and Gynecology, Gasthuisberg, Leuven, Belgium.
The process of embryo implantation includes attachment of the embryo to the endometrium and penetration through the epithelial layer, decidualization of the basement membrane, invasion of the uterine stroma and access to blood supply. This implantation process is very different in humans when compared to pigs, cattle or rodents. The process of invasion in humans where the embryo gets embedded in decidual tissue and in spiral arteries is more aggressive, but otherwise similar to the process of implantation and invasion in non-human primates such as rhesus monkeys and baboons. For ethical reasons, it is unacceptable to study directly the process of embryo implantation in women, and to this day, this remains one of the ‘black boxes’ of reproductive science. Indeed for many clinicians practicing reproductive medicine, in fertility centers, the most difficult question and of concern asked by patients is: ‘Why do my healthy appearing embryos not implant: is there a problem with my endometrium or uterus?’ The olive baboon (Papio anubis anubis) is an excellent animal model for reproductive research. In contrast with smaller non-human primates like rhesus monkeys or cynomolgus monkeys, it is possible in baboons to use transcervical uterine probes (curettes, catheters and hysteroscopic equipment) to perform endometrial biopsy, embryo flushing or transfer and hysteroscopy in a non-invasive way. This can be done easily in multiparous baboons during menstruation, but may be more difficult at the end of the follicular phase (maximal perineal swelling impedes vaginal/cervical access) or during the luteal phase (narrow cervix), in nulliparous baboons and in animals with abnormal internal genitals. In this paper we present an overview regarding the potential of the baboon model to study in vivo uterine receptivity and embryo implantation using invasive and non-invasive approaches. (c) 2007 S. Karger AG, Basel.
Semin Pediatr Surg. 2007 Nov;16(4):278-87.
Laparoscopy in uterovaginal anomalies.
Division of Pediatric Surgery, J P Garrahan Children’s Hospital, Buenos Aires, Argentina. email@example.com
Providing its excellent visualization, access to pelvic structures, and less postoperative adhesion, laparoscopy has been an important tool for the treatment of uterovaginal anomalies. We have used it to define the anomaly, monitor endometriosis or a hysteroscopic procedure, replace an absent vagina, and resect abnormal Müllerian structures. This article details the technique and reports the results of the use of operative laparoscopy for the treatment of uterovaginal anomalies in children and adolescents. The author’s experience demonstrates some”nonclassical” applications of endosurgery in the management of these anomalies in the pediatric age.
Lancet. 2007 Oct 13;370(9595):1392.
A growing, bleeding, violet mole.
Department of General and Visceral Surgery, Augusta Krankenanstalt, Academic Teaching Hospital, Ruhr-University Bochum, Germany. firstname.lastname@example.org
Ultrasound Obstet Gynecol. 2007 Nov;30(6):883-8.
Value of preoperative ultrasound examination in the selection of women with adnexal masses for laparoscopic surgery.
Early Pregnancy and Gynaecology Assessment Unit, King’s College Hospital, London, UK. email@example.com
OBJECTIVES: To assess the value of preoperative ultrasound examination in predicting the feasibility of intermediate-level laparoscopic surgery for benign adnexal masses. METHODS: Symptomatic women with a clinical or ultrasound diagnosis of adnexal mass were offered a detailed transvaginal ultrasound scan in order to assess the feasibility of laparoscopic cystectomy/oophorectomy. In all cases an attempt was made to establish a likely histological diagnosis using the pattern recognition method. The selection criteria for laparoscopic surgery were: no ultrasound features suggestive of ovarian cancer, predominantly cystic lesion with no solid foci > 5 cm in mean diameter, no evidence of severe pelvic endometriosis or severe pelvic adhesions and dermoid cyst < 10 cm in mean diameter. Laparoscopic surgery was classified as successful if the mass was removed completely without resorting to a laparotomy. RESULTS: One hundred and forty-three women were diagnosed with a total of 162 adnexal cysts. The final dataset consisted of 137 women (with 153 lesions), 113 (82.5%) of whom were selected for laparoscopy and 24 (17.5%) for laparotomy. On histological examination 152 (99.3%) cysts were benign and the remaining one (0.7%) was borderline. The operation was successfully completed laparoscopically in 107/113 (94.7%) cases. The preoperative ultrasound assessment predicted the successful outcome of laparoscopic surgery with a sensitivity of 98% (95% CI, 94-99%), specificity of 79% (95% CI, 60-90%), positive predictive value of 95% (95% CI, 89-98%), positive likelihood ratio of 4.58 (95% CI, 2.25-9.32) and negative likelihood ratio of 0.02 (95% CI, 0.01-0.09). CONCLUSIONS: A detailed preoperative transvaginal ultrasound examination is a helpful tool for assessing the feasibility of intermediate-level laparoscopic surgery in women with benign adnexal lesions.
Histopathology. 2007 Nov;51(5):721-3.
Endometrial glands and stroma within uterine smooth muscle proliferations: an introduction of the concept of an adenomyotic leiomyoma.
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2007 Sep;36(5):515-20.
[Research on minimal to mild endometriosis associated infertility][Article in Chinese]
The Affiliated Obstetrics and Gynecology HospitalìCollege of Medicine, Zhejiang University, Hangzhou, China.
Endometriosis is a common disease of reproductive age women and infertility is one of its clinical manifestations. Infertility of patients with severe endometriosis may be attributed to the anatomy alteration of pelvis.However, the infertility of patients with minimal to mild endometriosis whose pelvic anatomy remains intact is still hard to explain. It is considered that the infertility of patients with ninimal to mild endometriosis is associated with the alteration of the pelvic microenvironment. Several kinds of cytokines and proteins are involved in this process. They may disturb steps necessary to achieve successful pregnancy, such as ovulation,gamete transport, fertilization, embryo transport and implantation. Any disturbance to one of the steps mentioned above may lead to pregnant loss.
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2007 Sep;36(5):424-8.
[Increased nitric oxide levels in peritoneal fluids of minor-endometriosis patients and its relation to IVF-ET outcomes][Article in Chinese]
Department of Reproduction Endocrinology, The Affiliated Obstetrics and Gynecology Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
OBJECTIVE: To investigate the role of nitric oxide (NO) in the pathogenesis of early endometriosis-associated infertility. METHODS: The volume of peritoneal fluids was recorded and the concentration of NO in peritoneal fluid and serum was measured with a fluorescence method using 4, 5-diaminofluorescein (DAF-2) as an indicator, in 60 patients with early endometriosis-associated infertility ( endometriosis group), 60 patients with tubal infertility (tubal infertility group) and 20 patients without infertility (control group). The IVF-ET outcomes between patients with endometriosis and tubal infertility were compared. RESULT: The volume of peritoneal fluids from endometriosis group patients increased significantly compared with that in tubal infertility group patients and control groups. The concentration of NO in peritoneal fluid of the control group,the tubal infertility group and the endometriosis group was 9.98, 13.76 and 20.72, respectively (P<0.017). Furthermore the concentration of NO in serum of the patients of control group,tubal infertility group and endometriosis group was 12.25, 13.00, 13.60, respectively; there were no significant differences among these three groups. There were no significant differences in implantation rate, pregnancy rate and abortion rate of IVF-ET between endometriosis group patients and tubal infertility group patients. However, the fertilization rate was significantly lower in endometriosis group patients than that in tubal infertility group patients. CONCLUSION: Changes of nitric oxide in peritoneal fluids may play an important role in the pathogenesis of early endometriosis-associated infertility and IVF-ET may serve as an alternative method for this type of infertility.
Int J Biol Markers. 2007 Jul-Sep;22(3):203-5.
Elevation of serum CA 125 and D-dimer levels associated with rupture of ovarian endometrioma.
Department of Obstetrics and Gynecology, Faculty Hospital Nitra, Spitálska 6, 949 01 Nitra, Slovakia. firstname.lastname@example.org
BACKGROUND: Patients with endometriosis rarely have a serum CA 125 concentration >100 IU/mL. A raised plasma level of D-dimer indicates active fibrinolysis, either secondary to clot formation or primarily activated. This condition is seldom diagnosed in patients with endometriosis. CASE REPORT: A 53-year-old woman was referred to our institution for acute abdominal pain. Laparoscopic surgery revealed a large ovarian cyst with rupture on the left side. Preoperative laboratory tests detected high serum CA 125 and D-dimer levels. Adnexectomy was performed, resulting in a sharp decrease in serum CA 125 and D-dimer concentration. We describe the clinical course of the patient. CONCLUSION: Rupture of a large ovarian endometrioma can lead to a high serum concentration of CA 125, a condition which, in addition to the detected pelvic mass, may mimic a malignant process. The increased D-dimer plasma level indicated that a ruptured endometriotic cyst can induce coagulation reactions.
Int J Biol Markers. 2007 Jul-Sep;22(3):200-2.
Evaluation of serum CA 125 levels in patients with pelvic pain related to endometriosis.
I-II Units of Obstetrics and Gynecology, Civic Hospital, Via Carlo Goldoni 9/10, 90145 Palermo, Italy. email@example.com
The aim of the study was to investigate the clinical value of the serum CA 125 level for diagnosing and determining the severity of endometriosis and pelvic pain associated with endometriosis. Eighty-six women who underwent operative laparoscopy were enrolled. Sixty-nine women with endometriosis and 17 without endometriosis participated in this study. In all of the patients, endometriosis was diagnosed and classified into stages according to the Revised American Fertility Society (R-AFS) classification. The mean serum CA 125 levels were determined in each patient. We also investigated the relationship between serum CA 125 concentration and the intensity of dysmenorrhea and dyspareunia in the study group. The mean serum CA 125 levels of women with endometriosis were higher than those of the control group (p<0.050). However, the mean serum CA 125 levels were higher in stage IV than in other stages of endometriosis according to the R-AFS classification. On the other hand, the percentage of patients with serum CA 125 levels >35 U/mL was elevated in the subgroups with severe dyspareunia and severe dysmenorrhea versus the asymptomatic subgroup but the differences had no statistical significance. In conclusion, CA 125 serum levels were related to endometriosis and R-AFS score in the evaluated patient series. No correlation was found between serum levels of CA 125 and pelvic pain in patients with endometriosis.
Hum Reprod. 2007 Dec;22(12):3139-47. Epub 2007 Oct 5.
Endometrial cells from women with endometriosis have increased adhesion and proliferative capacity in response to extracellular matrix components: towards a mechanistic model for endometriosis progression.
Nuffield Department of Obstetrics and Gynaecology, Level 3, The Women’s Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK.
BACKGROUND: Endometriosis, classified as the presence of endometrial cells in ectopic sites, is a debilitating disease causing pain and infertility in approximately 10% of women of reproductive age. It is associated with the aberrant expression of extracellular matrix (ECM) components and their receptors, integrins. METHODS: We analysed the expression of integrins in stromal cells derived from peritoneal, ovarian and deeply infiltrating endometriotic lesions and from endometrium from women with and without endometriosis in vitro, using quantitative immunocytochemistry. The adhesive and proliferative capacity of each of the cell types in response to ECM components was assessed by in vitro assays of cell attachment and DNA synthesis. RESULTS: We demonstrate that eutopic and ectopic endometrial stromal cells from women with endometriosis exhibit an aberrant integrin profile in vitro compared with stromal cells derived from healthy controls. In addition, the former display increased adhesion and proliferative capacity in response to specific ECM components. CONCLUSIONS: We propose that the increased adhesive and proliferative potential of cells from endometriotic lesions may be a key feature in the pathogenesis of endometriosis. Furthermore, the elevated responsiveness of eutopic cells from women with endometriosis may contribute to the predisposition of some women to the disease.
Hum Reprod. 2007 Dec;22(12):3148-58. Epub 2007 Oct 6.
Estrogen metabolizing enzymes in endometrium and endometriosis.
Research Institute GROW, University Hospital Maastricht/University Maastricht, Peter Debyelaan, The Netherlands.
BACKGROUND: Estradiol (E(2)) is an important promoter of the growth of both eutopic and ectopic endometrium. The findings with regard to the expression and activity of steroidogenic enzymes in endometrium of controls, in endometrium of endometriosis patients and in endometriotic lesions are not consistent. METHODS: In this study, we have looked at the mRNA expression and protein levels of a range of steroidogenic enzymes [aromatase, 17beta-hydroxysteroid dehydrogenases (17beta-HSD) type 1, 2 and 4, estrogen sulfotransferase (EST) and steroid sulfatase (STS)] in eutopic and ectopic endometrium of patients (n = 14) with deep-infiltrative endometriosis as well as in disease-free endometrium (n = 48) using real-time PCR and immunocytochemistry. In addition, we evaluated their menstrual cycle-related expression patterns, and investigated their steroid responsiveness in explant cultures. RESULTS: Aromatase and 17beta-HSD type 1 mRNA levels were extremely low in normal human endometrium, while mRNAs for types 2 and 4 17beta-HSD, EST and STS were readily detectable. Only 17beta-HSD type 2 and EST genes showed sensitivity to progesterone in normal endometrium. Types 1 and 2 17beta-HSD and STS protein was detected in normal endometrium using new polyclonal antibodies. CONCLUSIONS: In endometriosis lesions, the balance is tilted in favor of enzymes producing E(2). This is due to a suppression of types 2 and 4 17beta-HSD, and an increased expression of aromatase and type 1 17beta-HSD in ectopic endometrium.