Arkh Patol. 2008 Sep-Oct;70(5):8-12.

[Clinical and morphological parallels and molecular aspects of the morphogenesis of adenomyosis]

[Article in Russian]

Kogan EA, Unanian AL, Demura TA, Grechukhina OM, Sidorova IS, Kiselev VI.

The purpose of the study was to reveal clinical and morphological parallels and to define molecular mechanisms, the regulation of proliferation, apoptosis, neoangiogenesis, and the extent of abnormal tissue in adenomyosis (AM). The surgical material obtained from 492 patients of late reproductive age was examined. The data of clinico-anamnestic and instrumental diagnostic studies and a morphological study with hematoxylin and eosin staining were analyzed. An immunohistochemical study was carried out on serial paraffin sections (n = 115), by applying antibodies to Apo-CAS, Ki67, PCNA, CD-34, MMP-1, MMP-2, MMP-7, MMP-9, TIMP-1, TIMP-3, TIMP-4, and E-cadherin. The specific features of their morphological structure and the clinical course of the disease allowed identification of its active and inactive forms. Immunohistochemically active AM is characterized by high proliferation, diminished apoptosis, and increased expression of MMPs along with lower expression of TIMPs by glandular and stromal cells as compared with inactive AM. At the same time, there was a high activity of stromal cells in the foci of active AM. The results of the study may be used to predict the course of the disease and to elaborate target therapy for AM.

Taiwan J Obstet Gynecol. 2008 Dec;47(4):384-90.

Differential diagnosis of gynecologic organ-related diseases in women presenting with ascites.

Cheng MH, Yen MS, Chao KC, Sheu BC, Wang PH.

Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, and Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.

Ascites is a pathologic accumulation of fluid within the peritoneal cavity, and usually develops as a result of liver disease, congestive heart failure or nephrotic syndrome. Ascites is also a common manifestation of some gynecologic diseases. It is important that health care workers consider gynecologic problems among the potential differential diagnoses in patients presenting with ascites. Various kinds of ovarian diseases, such as epithelial ovarian cancer, benign ovarian fibroma, stromal hyperplasia, ovarian hyperstimulation syndrome, primary peritoneal serous carcinoma, endometriosis and peritoneal tuberculosis, should be kept in mind when women are found to have ascites.

Int J Nurs Pract. 2008 Dec;14(6):443-8.

The impact of endometriosis on work and social participation.

Gilmour JA, Huntington A, Wilson HV.

School of Health and Social Services, Massey University at Wellington, Wellington, New Zealand. j.a.gilmour@massey.ac.nz

Endometriosis is a debilitating chronic disease that can affect many aspects of everyday life owing to symptoms such as pain and fatigue. This paper reports the findings of a study exploring the impact of symptomatic endometriosis on women’s social and working life. The study used a feminist approach. Eighteen women were interviewed and a thematic approach used to analyse the data. The analysis is structured around three themes focusing on issues around disclosure of symptoms in the work place; the impact of symptoms on work, education and social participation; and the strategies used by women in the study to manage endometriosis. A range of health and employment implications are discussed in this paper. In particular, nurses can provide useful support to women by careful assessment and prompt referral for diagnostic procedures and by providing timely and comprehensive information, including information about the lifestyle and nutritional factors recommended by women with endometriosis.

Turk J Gastroenterol. 2008 Dec;19(4):294-6.

Rectosigmoid endometriosis.

Erkan N, Calişkan C, Yildirim Y, Vardar E, Korkut M.

Int J Surg Pathol. 2008 Dec 30. [Epub ahead of print]

Diffusely Infiltrating Endometrial Carcinomas With No Stromal Response: Report of a Series, Including Cases With Cervical and Ovarian Involvement and Emphasis on the Potential for Misdiagnosis.

Kalyanasundaram K, Ganesan R, Perunovic B, McCluggage G.

Endometrial carcinomas, particularly of endometrioid type, can invade the myometrium or cervix without eliciting a stromal desmoplastic or inflammatory response and have been referred to as diffusely infiltrating endometrial carcinomas. This study describes a series of 14 endometrial carcinomas infiltrating as single “naked” glands without a stromal response. The neoplasms consisted of 12 endometrioid carcinomas, 1 mixed endometrioid and clear cell carcinoma, and 1 serous carcinoma. In all cases, there was myometrial invasion without stromal response. Seven cases exhibited cervical stromal involvement and in 2 there was involvement of both ovaries in a similar pattern.Several of the cases were seen in consultation and the pattern of infiltration raised a number of differential diagnoses, both benign and malignant, depending on the site of tumor involvement, including adenomyosis, adenomyoma, primary endocervical glandular lesions, cervical mesonephric remnants, endometriosis or tuboendometrioid metaplasia, and ovarian cortical inclusion cysts. Although this pattern of invasion has been reported previously, it continues to present diagnostic difficulties.

ScientificWorldJournal. 2008 Dec 25;8:1325-7.

Inhibition of steroid sulfatase activity in endometriotic implants by STX64 (667Coumate): a potential new therapy.

Fusi L, Purohit A, Brosens J, Woo LW, Potter BV, Reed MJ.

Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Hospital, London, UK. l.fusi@imperial.ac.uk

Endometriosis is a common and debilitating condition of women in their reproductive age that is associated with pain and infertility. Current medical treatments are only partially effective and associated with wide-ranging side effects. New understanding of local estrogen production by endometriotic tissue and the availability of powerful suppressing drugs may herald a new era in the treatment of this condition.

Acta Dermatovenerol Croat. 2008;16(4):218-21.

Endometriosis of umbilical cicatrix: case report and review of the literature.

Rosina P, Pugliarello S, Colato C, Girolomoni G.

Department of Biomedical and Surgical Science, University of Verona, Verona, Italy. prosina@yahoo.com

Umbilical endometriosis has an estimated incidence of 0.5%-1% of all patients with endometrial ectopia. It is a very rare disease, but should be considered on the differential diagnosis of umbilical lesions. We report on a case of spontaneous umbilical endometriosis in a 38-year-old woman, with a dark brown nodule periodically bleeding, associated with severe abdominal pain. There was no history of endometriosis and she had not been pregnant before. Laparoscopic visualization of pelvic cavity showed bilateral ovarian endometrioma (it was removed while sparing the ovaries). Surgical treatment proved effective. Cutaneous endometriosis could be a sign of internal endometriosis. Presentations may be atypical and pose diagnostic difficulty, mimicking other acute diseases, e.g., skin neoplasm, folliculitis, etc., but it should be suspected in any female presenting with a painful or bleeding mass close to the umbilicus or abdominal surgical scar.

N Engl J Med. 2008 Dec 25;359(26):2844; author reply 2844-5.

Comment on:

N Engl J Med. 2008 Sep 11;359(11):1136-42.

Gonadotropin-releasing hormone agonists for endometriosis.

de Ziegler D, Borghese B, Chapron C.

J Radiol. 2008 Nov;89(11 Pt 1):1745-54.

[MR imaging features of deep pelvic endometriosis: correlation with laparoscopy]

[Article in French]

Jarlot C, Anglade E, Paillocher N, Moreau D, Catala L, Aubé C.

Département de Radiologie, CHU d’Angers, 4 rue Larrey, 49033 Angers Cedex 01, France. crous@hotmail.fr

Deep pelvic endometriosis is an invalidating disorder affecting the retrocervical region, rectosigmoid colon and urinary bladder generally requiring surgical management. MRI is the preoperative imaging modality of choice. The purpose of this paper is to describe the MR imaging features of deep pelvic endometriosis with laparoscopic correlation. METHODS: Thirty-five patients with clinical suspicion of deep pelvic endometriosis underwent pelvic MRI. Results of MRI, including morphological and signal characteristics features of the lesions were compared to laparoscopic fidings. RESULTS: Laparoscopy detected lesions of deep pelvic endometriosis of the uterosacral ligaments (n=10), torus uterinum (n=9), rectosigmoid (n=11), Douglas pouch (n=9), recto-vaginal septum (n=6), bladder (n=4) and posterior vaginal cul-de-sac (n=2). The sensitivity, specificity, positive predictive value and negative predictive value of MRI were assessed for each localization. CONCLUSION: MRI allows diagnosis of deep pelvic endometriosis of the bladder, rectosigmoid and Douglas pouch and with lower sensitivity for lesions of the uterosacral ligaments, posterior vaginal cul-de-sac and rectovaginal septum.

J Radiol. 2008 Nov;89(11 Pt 1):1695-6.

[Evaluation of pelvic endometriosis: the role of MRI]

[Article in French]

Bazot M, Daraï E.

J Environ Pathol Toxicol Oncol. 2008;27(4):307-20.

Photodynamic diagnosis and therapy in gynecology.

Soergel P, Löning M, Staboulidou I, Schippert C, Hillemanns P.

University Women’s Hospital, Hanover Medical School, Hanover, Germany.

Photodynamic diagnosis (PDD) and therapy (PDT) are modern methods that are evaluated in different fields in gynecology. PDD is currently under investigation in gynecologic conditions such as cervical intraepithelial neoplasia (CIN), vulvar intraepithelial neoplasia (VIN), endometriosis, and ovarian cancer. PDT has been successfully evaluated in HPV-related genital dysplasia such as CIN and VIN, in genital warts, in local recurrent breast cancer, and for endometrial ablation. The aim of this review is to give an overview about current applications.

Surg Laparosc Endosc Percutan Tech. 2008 Dec;18(6):622-5.

A case of endometriosis of the appendix with adhesion to right ovarian cyst presenting as intussusception of a mucocele of the appendix.

Akagi T, Yamamoto S, Kobayashi Y, Fujita S, Akasu T, Moriya Y, Kato T.

Division of Colorectal Surgery, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan.

Endometriosis of the appendix is rare, and we present a case of endometriosis of the appendix with adhesion to right ovarian cyst presenting as intussusception of a mucocele of the appendix in a 35-year-old woman with no associated sign of endometriosis. Colonoscopy revealed intussusception-like change and mucosal defect in the mucosa at the orifice of the appendix. Abdominal computed tomography showed a low-density lesion, which seemed to be right ovarian cyst. However, as the appendix was located near this site, differentiation between ovarian cyst and mucocele of the appendix was difficult. Laparoscopic examination disclosed blue berry spots on the Douglas cul-de-sac and right ovarian cyst, and the appendix was atrophied and hardened and tightly adhered to the right ovary. Laparoscopic appendectomy and partial cecectomy was performed, and on pathologic examination, thickening and fibrosis of the muscle layer owing to endometriosis were judged to have caused intussusception-like changes.

J Pharmacol Sci. 2008 Dec;108(4):422-5.

Basic and translational research on proteinase-activated receptors: proteinase-activated receptors in female reproductive tissues and endometriosis.

Osuga Y, Hirota Y, Taketani Y.

Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Japan. yutakaos-tky@umin.ac.jp

During the menstrual cycle, dynamic morphological changes are observed in the ovarian follicle and the endometrium. These changes are associated with the onset of the inflammatory response in which many proteinases play various roles. Thrombin-induced activation of PAR(1) (proteinase-activated receptor 1) stimulates the production of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) in human granulosa cells, suggesting a possible role for PAR(1) in the ovulatory process. In the endometrium, PAR(2) expression increases during the menstrual period. PAR(2) activation induces IL-8 production and cell proliferation in human endometrial stromal cells. PAR(1) also stimulates proinflammatory cytokine production in human endometrial stromal cells. Thus, the PARs may be important in directing the dynamic changes of the endometrium. PARs also appear to play a role in endometriosis, a common gynecological disease, since activation of PAR(1) and PAR(2) induces the secretion of inflammatory cytokines and the proliferation of stromal cells in endometriotic lesions. Taken together, PARs appear to play diverse roles in the human reproductive organs.

Chang Gung Med J. 2008 Sep-Oct;31(5):431-40.

Medical treatment of endometriosis.

Huang HY.

Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taipei, Chang Gung University College of Medicine, Taoyuan, Taiwan. hongyuan@cgmh.org.tw

Endometriosis is a common, benign and chronic gynecological disorder. It is also an estrogen-dependent disorder that can result in substantial morbidity, including pelvic pain, pro gressive dysmenorrhea, dyspareunia, infertility and repeat surgeries. Endometriosis is often treated surgically upon diag nosis but with a higher rate of recurrence, suggesting that a combination of surgical and medical management might provide better outcomes. The primary goal of medical treatment for endometriosis is to halt the growth and activity of endometriosis lesions. The most widely utilized medical treat ment for endometriosis involves use of gonadotropin-releasing hormone (GnRH) agonists and oral contraceptives. Conventional agents also include androgen derivates and progestins. Due to the chronic nature of this disease, long-term or Dr. Hong-Yuan Huang repeated courses of medication may be required to control its related symptoms. Increasing knowledge about the pathogenesis of endometriosis at the cellular and molecular levels may give us the opportunity to use new, specific agents for treatment, including aromatase inhibitors, progesterone antagonists, selective progesterone receptor modulators, GnRH antagonists, intrauterine releasing systems with progestin and new pharmaceutical agents affecting inflammation, angiogenesis, and matrix metalloproteinase activity. Many of these promising new agents may prevent or inhibit the development of endometriosis. Further clinical trials may determine if these new therapies are superior to current medical treatment strategies for endometriosis.

J Reprod Med. 2008 Nov;53(11):881-2.

Abdominal wall endometrioma following cesarean delivery: a case report.

Kesterson JP, Justice T, Terrassa M, Cook C.

Division of Gynecologic Oncology, Roswell Park Cancer Center, Buffalo, New York 14263, USA. joshuapkesterson@yahoo.com

BACKGROUND: Rarely, endometriosis occurs in an abdominal wall scar after a cesarean delivery. CASE: This case report summarizes the presentation, diagnosis and treatment of a woman with an abdominal wall endometrioma within a cesarean delivery skin incision scar. CONCLUSION: An abdominal wall endometrioma needs to be considered in the differential diagnosis of any woman of reproductive age presenting with a painful abdominal wall mass and a history of uterine surgery via an abdominal incision.

Zhonghua Bing Li Xue Za Zhi. 2008 Sep;37(9):643-4.

[Adenosarcoma arising in abdominal scar endometriosis: report of a case]

[Article in Chinese]

Yang F, Yang KX, Yao XY, Gong J, Song B.

Zhonghua Bing Li Xue Za Zhi. 2008 Sep;37(9):584-8.

[Study on expression of estrogen receptor isoforms in eutopic and ectopic endometrium of ovarian endometriosis]

[Article in Chinese]

Liu AJ, Guan Z, Zhang ZM, Wei LX, Li YL.

Department of Pathology, Chinese People’s Liberation Army General Hospital, Beijing 100853, China. aliu301@yahoo.com.cn

OBJECTIVE: To investigate the distribution of ER isoforms in endometriosis and eutopic endometrium. METHODS: Tissue samples of patients with ovarian endometriosis, treated in People’s Liberation Army General Hospital from January 2004 to December 2006, were retrieved. A total of 60 cases of ovarian endometriotic cysts with their corresponding eutopic endometrium (30 cases of proliferation phase and 30 of secretary phase eutopic endometrium) and 30 cases of normal endometrium (15 proliferative and 15 secretary phase endometrial samples respectively) were included. Expressions of ERalpha and ERbeta were analyzed using immunohistochemistry and the expression ratio was statistically analyzed by using SPSS 12.0 software. RESULTS: Expressions of both ERalpha and ERbeta in epithelial cells were positively correlated with that of the stromal cells. The expression of ERalpha in eutopic endometrium (73.3% in epithelium and 76.7% in stroma) was significantly higher than that in ovarian endometriotic cysts (43.3% in epithelium and 46.7% in stroma), or normal control (56.7% in epithelium and 50.0% in stroma, respectively, each P < 0.05. However, the expression of ERbeta (90.0% in epithelium and 76.7% in stroma) was higher in ovarian endometriotic cysts than that in the eutopic endometrium (68.0% in epithelium and 63.3% in stroma respectively, P < 0.05), and ERbeta expression in eutopic endometrium was higher than that in the normal control endometrium (36.7% in epithelium and 26.7% in stroma, respectively, P < 0.05). The expressions of both ERalpha and ERbeta changed periodically in eutopic and normal endometrium, whereas ERalpha and ERbeta level were less variable in the ectopic endometrium. The expression of ERbeta was statistically higher than that of ERalpha (P < 0.05) in ectopic endometrium, whereas no significant difference was seen between the two isoforms in the eutopic or normal endometrium. CONCLUSIONS: Both ERalpha and ERbeta have higher expression levels in eutopic endometrium of patients with ovarian endometriotic cysts. ERbeta is predominantly expressed in endometriotic cysts, where the expression of ERalpha is limited. The different distribution of ERalpha and ERbeta may play an important role in the development of ovarian endometriosis.

Reprod Sci. 2008 Dec;15(10):1066-74.

Concentrations of receptor for advanced glycation end products, VEGF and CML in plasma, follicular fluid, and peritoneal fluid in women with and without endometriosis.

Fujii EY, Nakayama M, Nakagawa A.

Division Director of Obstetrics & Gynecology, Reproductive Sciences, National Center for Child Health and Development, Tokyo, Japan. perky.ef@gmail.com

The etiology and pathogenesis of endometriosis is largely unknown. It has been reported that advanced glycation end products-receptor for advanced glycation end products regulation relates to oxidative stress, inflammatory reaction, apoptosis, and angiogenesis through vascular endothelial growth factor activation. The purpose of this study was to examine whether advanced glycation end products-receptor for advanced glycation end products regulation contributes to the pathogenesis of endometriosis. Plasma, follicular, and peritoneal fluid samples were collected from women with or without endometriosis, and soluble receptor for advanced glycation end products, vascular endothelial growth factor and carboxymethyl lysine levels were measured by enzyme-linked immunosorbent assay. Vascular endothelial growth factor and soluble receptor for advanced glycation end products concentrations were similar in plasma; however, their concentrations in follicular fluid were significantly increased in endometriosis patients (soluble receptor for advanced glycation end products was 132 + 31 pg/mg of protein vs. 105 + 27 pg/mg; vascular endothelial growth factor was 70 + 3 pg/mg vs. 49 + 18 pg/mg, expressed as the mean + standard deviation). Increased soluble receptor for advanced glycation end products and vascular endothelial growth factor levels in a local environment suggest that the advanced glycation end products-receptor for advanced glycation end products may contribute to the pathogenesis of endometriosis.

Reprod Sci. 2008 Dec;15(10):993-1001.

The expression and ovarian steroid regulation of endometrial micro-RNAs.

Toloubeydokhti T, Pan Q, Luo X, Bukulmez O, Chegini N.

Division of Reproductive Endocrinology & Infertility, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville, Florida 32610, USA.

MicroRNAs (miRNAs) which regulate gene expression stability displayed an aberrant expression profile in ectopic endometrium (ECE) as compared to eutopic (EUE) and normal endometrium (NE). We assessed the expression of miR-17-5p, miR-23a, miR-23b and miR-542-3p, their predicted target genes, steroidogenic acute regulatory protein, aromatase and cyclooxygenase-2, and influence of ovarian steroids on their expression in endometrial stromal (ESC) and glandular epithelial cells (GEC). The results indicated a lower expression of miR-23b and miR-542-3p and higher level of miR-17-5p in paired ECE and EUE as compared with NE. These levels were elevated and inversely correlated with the level of expression of their respective target genes in ECE. The expression of these miRNAs and genes was differentially regulated by 17beta- estradiol, medroxyprogesterone acetate, ICI-182780 and RU-486, or their respective combinations in ESC and GEC. We concluded that altered expression of specific miRNAs in ECE, affecting the stability of their target genes expression, has direct implications in pathogenesis of endometriosis.

Zhonghua Fu Chan Ke Za Zhi. 2008 Nov;43(11):831-4.

[Atypical endometriosis: a clinicopathologic study of 163 cases]

[Article in Chinese]

Guo DH, Pang SJ, Shen Y.

Department of Pathology, Tianjin Central Obstetrics and Gynecology Hospital, Tianjin 300052, China. dhuiguo@sina.com

OBJECTIVE: To investigate the clinicopathologic features of atypical endometriosis (AEM) and to discuss the relationship between AEM and tumors. METHODS: A retrospective analysis was performed of 163 cases of AEM, which were retrieved from the Department of Pathology files at the Tianjin Central Obstetrics and Gynecology Hospital between Jan 2004 and Dec 2006. The pathologic changes of AEM including its glandular epithelium, stroma, background and the conditions coexisting with tumor were observed. RESULTS: The AEM accounted for 4.38% (163/3724) of the endometriosis (EM) cases. Of 172 AEM foci of 163 patients, 168 were in the ovary, and the other 4 were in the fallopian tube, cervix and uterine serosa respectively. The rate of ovarian AEM was 6.81% of endometriosis. AEM associated with tumour was found in 26 cases (15.95%) and among 27 of ovarian AEM, 15 were malignant, 9 borderline and 3 benign. The AEM epithelia were mainly arranged in the form of surface epithelium. They present with characteristic features of moderate to marked pleomorphism, epithelial tufting and bud structures by microscopy. The walls of AEM cyst were presented with three layers of epithelium, endometrioid stroma and fibrosis-collagen. The endometrioid stroma were usually thin in contrast to the fibro-collagen tissue, which was often thick with scarred background. The transformation from AEM to tumor was found in most of the malignant tumors (14/15, 93%). CONCLUSIONS: AEM lesions hold some features of both EM and tumor, which may have a relatively higher potential for tumorigenesis and canceration. The process of damage and repair in EM foci during a long course may play a role in the development of EM into AEM and finally into tumor.

Eur J Radiol. 2008 Dec 10. [Epub ahead of print]

Long-term results of symptomatic fibroids treated with uterine artery embolization: In conjunction with MR evaluation.

Kim MD, Lee HS, Lee MH, Kim HJ, Cho JH, Cha SH.

Department of Diagnostic Radiology Bundang CHA General Hospital, Pochon CHA University, Republic of Korea.

OBJECTIVE: The aim of the present study is to determine long-term clinical efficacy of uterine fibroid embolization (UFE) for symptomatic fibroids in conjunction with MR evaluation. MATERIALS AND METHODS: Sixteen patients with a follow-up period of 4 years or longer were analyzed retrospectively. Ages ranged from 27 to 45 (mean 39.5) years. Mean follow-up periods were 5.8 years (range: 4.1-6.9 years). The symptom changes, in terms of menorrhagia and dysmenorrhea and bulk-related symptoms, were assessed. The primary embolic agent was polyvinyl alcohol particle (250-710mum). All patients underwent preprocedural and long-term follow up MR imaging. Uterine volumes were calculated using MRI. RESULTS: Symptom improvements were reported for menorrhagia (8/9, 88.9%), dysmenorrhea (5/5, 100%), and bulk-related symptoms (7/9, 77.8%) at long-term follow up. Two patients (12.5%) had symptom recurrences at long-term follow-up. Tumor regrowth from incomplete infarction was a cause of recurrence in one patient and newly developed leiomyomas in the other one. One patient underwent hysterectomy because endometriosis developed 4 years after UFE. Of the 14 necrotic myomas on short-term follow up MR after UFE, eight (57.1%) demonstrated maintaining necrosis with further shrinkage and six (42.9%) were no longer visualized on long-term follow up MR images. Overall, the mean volume reduction rates of the predominant fibroid and uterus were 80.5%, 36.7% at long-term follow up, respectively. CONCLUSION: UFE is an effective treatment for symptomatic fibroids with an acceptable long-term success rate. Long-term MR imaging after UFE revealed persistent necrotic fibroid, non-visualization of fibroids and tumor regrowth when incompletely infarcted.

Zhonghua Yi Xue Za Zhi. 2008 Jul 29;88(29):2045-8.

[Differential expressed genes in eutopic endometrium of endometriosis patients: comparison between Uygur and Han women in Xianjiang]

[Article in Chinese]

Aixingzi A, Ding Y, Ma JQ, Chen ZF.

Department of Gynecology, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China.

OBJECTIVE: To investigate the reason why the incidence of endometriosis (EM) is lower in the Uygur women than in the Han women. METHODS: Eutopic and ectopic endometrium samples were obtained by operation and biopsy from 26 EM patients, 10 Uygur women and 16 Han women and analyzed with a gene expression microarray containing the cDNAs of 22 000 human genes. Twenty-two women, 10 Uygur and 12 Han, were used as controls. RESULTS: Eleven differentially expressed genes, 7 up-regulated and 6 down-regulated, were screened out from the eutopic endometrium of the Uygur women with EM. 58 differential expressed genes were screened out from the in eutopic endometrium of the Han women with EM, 53 being up-regulated and 5 down-regulated. Five genes were screened out in both groups, 3 being up-regulated and 2 down-regulated. CONCLUSION: The number of differentially expressed genes of the Uygur women with EM is lower than that of the Han women with EM, which may be the cause of relative low incidence of EM among Uygur women.

Recent Pat Inflamm Allergy Drug Discov. 2008;2(2):128-38.

Recent knowledge and new pharmaceutical products in potential alleviation of endometriosis.

Vassiliadis S, Athanassakis I.

Department of Biology, University of Crete, Heraklion, Crete, Greece.

Endometriosis is so far considered as an incurable inflammatory disease. The ectopical implants of endometrial cells proliferate, increase in size and thereafter bleed following the menstrual cycle. The accumulated blood aggravates the situation by developing into cysts which, depending on the place, size and number, in most cases increase pain. Infertility in endometriosis is related either to mechanical distortion of the reproductive truck or to various endometriosis-induced factors including hormones, cytokines and chemokines. Except from the anti-inflammatory treatments and gonadotropin-releasing hormone agonists that have been used for a long time to relief from pain, new treatments are targeted against either hormonal-mediated cell growth via inhibition of the metabolic pathway of estrogens and androgens or vascularization or even implantation of the endometrial engraftment. Thus, the role of selective estrogen, androgen or progesterone receptor modulators, aromatase inhibitors, vascular endothelial growth factor receptor and extracellular matrix modulators is reviewed. This article also reviewed recent patents related to the field.

Womens Health (Lond Engl). 2008 Jul;4(4):399-411.

Dysmenorrhea: risk factors in women with endometriosis.

Liu X, Guo SW.

Fudan University, Deptartment of Gynecology, Shanghai OB/GYN Hospital, Shanghai, China. lxsdoc@hotmail.com

Although it is generally accepted that endometriosis is responsible for dysmenorrhea, as well as other symptoms such as infertility, the precise relationship between the severity of dysmenorrhea and various characteristics of disease, such as stage and the type or site of endometriotic lesions, has been elusive and often a matter of heated debate, owing largely to conflicting reports. Here we review factors that are reported to be associated with dysmenorrhea in endometriosis. We also demonstrate, through a real example, that different statistical models employed in data analyses may yield somewhat different sets of risk factors, and the difference may not be always resolved within the same data set. In addition, we make the point that despite the best-fitting models, there may still be a sizable portion of variation in the severity of dysmenorrhea that can not be explained completely by the identified risk factors, suggesting that factors other than those of surgical findings or patient characteristics may also be responsible for dysmenorrhea severity. We review some possible factors that may also be responsible for the risk and severity of dysmenorrhea. Finally, we expose areas in need of further research.

Womens Health (Lond Engl). 2008 May;4(3):269-80.

Effects of antiprogestins on the uterus.

Ouzounian S, Bouchard P, Chabbert-Buffet N.

Hospital St Antoine APHP, Endocrinology Unit, Paris, France.

Progesterone-receptor modulators (PRMs) are progesterone-receptor ligands that can exert agonistic, antagonistic or mixed agonist-antagonist effects depending on the cellular context. The mechanisms of action of these compounds are still incompletely understood. PRMs already have several applications in women’s health such as emergency contraception, pregnancy termination, management of early fetal demise and cervical maturation. The main indications that will be developed in the future include dysfunctional bleeding and preoperative treatment of uterine myomas. Other future indications may include estrogen-free contraception, treatment of endometriosis and prevention and treatment of breast cancer. However, the available data from mid- to long-term continuous administration studies has raised the issue of endometrial safety. For this reason, long-term applications of PRMs are currently postponed, although windows of treatment with a short course of progestin therapy, or even by a short interruption of treatment, could improve endometrial aspects if needed.

Can Assoc Radiol J. 2008 Oct;59(4):210-2.

Answer to case of the month #136. Endometrioma of the rectus sheath after Caesarean section.

Feeney J, Govender P, Snow A, Torreggiani WC.

Department of Radiology, The Adelaide and Meath Hospital, Tallaght, Dublin 24, Ireland.

Ginecol Obstet Mex. 2008 Nov;76(11):679-84.

[Hysteroscopy used in infertility. Diagnosis and therapy]

[Article in Spanish]

Alanís Fuentes J, Pérez Ramírez Mde L.

Servicio de Salud Reproductiva, Hospital Dr. Manuel Gea González, SS. josealanisfuentes@yahoo.com.mx

The purpose of this study is to review the prevalence of different uterine defects associated with infertility, recurrent pregnancy loss, and preterm pregnancies. Various infertility etiologies are analyzed, mainly that of uterine basis (adhesions, septa, myomas, polyps, pelvic inflammations or infection, and endometriosis). Importance of surgical techniques with minimal invasion is studied, basically hysteroscopy as a diagnosis and therapeutic method, which is compared with the rest of techniques.

J Matern Fetal Neonatal Med. 2008 Dec;21(12):924-6.

Spontaneous hemoperitoneum in a twin pregnancy complicated by endometriosis.

Roche M, Ibarrola M, Lamberto N, Larrañaga C, García MA.

Obstetricia y Ginecologia, Hospital Virgen del Camino, Pamplona, Spain.

Endometriosis is a common gynecologic condition in reproductive age. It is commonly believed that pregnancy has beneficial effects on endometriosis by reducing the symptoms. Although severe endometriosis is commonly associated with infertility, assisted reproductive technology such as ‘in vitro fertilisation-embryo transfer’, enables more patients with severe endometriosis to conceive. CASE: A primigravida with a twin pregnancy presented acute abdominal pain and hypovolemic shock at 33 weeks of gestation. Ultrasound examination revealed the absence of fetal heartbeat in one fetus and serious bradycardia in the other without echographic signs of placental abruption. Immediate laparotomy revealed massive hemoperitoneum resulting from spontaneous rupture of right uterine vessels. Two demised fetuses were delivered by cesarean section and hemostasis was accomplished. According to the literature reported, endometriosis may be involved in the rupture of these vessels.

J Obstet Gynaecol. 2008 Oct;28(7):742-5.

Clinical characteristic analysis of 32 patients with abdominal incision endometriosis.

Zhu Z, Al-Beiti MA, Tang L, Liu X, Lu X.

Obstetrics and Gynecology Hospital at Fudan University, Shanghai, China.

Medical records of 32 women with abdominal incision endometriosis who underwent surgical treatment in the Obstetrics and Gynaecology Hospital at Fudan University between September 1999 and March 2006 were reviewed retrospectively. All cases concerning the diagnosis of endometriosis were confirmed by two gynaecological pathologists. The median age was 32 years (range from 25 to 45). A total of 31 patients had a history of caesarean section, and one case underwent ovarian endometrioid cystectomy. All abdominal incision endometriosis presented with a mass in the abdominal scar. Among them, there were 30 patients who complained of cyclical pain during menses. All of the 32 cases underwent surgical treatment and had follow-up from 10 months to 6 years; there was no recurrence of endometriosis in 31 cases. Abdominal incision endometriosis is rare in women and most cases present following caesarean section. It is suggested that during caesarean section, precautions need to be taken to avoid transplantation of endometrium into the abdominal incision. Surgical treatment is recommended to excise the lesion completely. The frozen section is performed during the operation due to the possibility of malignancy in abdomen incision endometriosis.

Fertil Steril. 2008 Dec 3. [Epub ahead of print]

Pain and ovarian endometrioma recurrence after laparoscopic treatment of endometriosis: a long-term prospective study.

Porpora MG, Pallante D, Ferro A, Crisafi B, Bellati F, Benedetti Panici P.

Department of Gynecology and Obstetrics, University of Rome “Sapienza,” Rome, Italy.

OBJECTIVE: To identify prognostic factors for pain and endometrioma recurrence after complete laparoscopic excision of endometrioma(s). DESIGN: Prospective observational study. SETTING: Tertiary care university hospital. PATIENT(S): One-hundred sixty-six consecutive women affected by uni- or bilateral ovarian endometrioma(s). INTERVENTION(S): Laparoscopic conservative treatment of endometriosis. MAIN OUTCOME MEASURE(S): Patient demographic characteristics, surgical findings, and surgical results were prospectively recorded. Postoperative follow-ups were carried out every 3 months to identify pain and/or endometrioma recurrence for a minimum of 3 years. RESULT(S): Dysmenorrheal, dyspareunia, and chronic pelvic pain recurred in 14.5%, 6%, and 5.4% of women, respectively. Prior surgery for endometriosis, adhesion extension, and use of ovarian stimulation drugs (OSD) were unfavorable prognostic factors for pain symptoms. Ovarian endometrioma recurred in 9.6% of cases; negative factors were prior surgery for endometriosis, OSD, pelvic adhesions, and high American Society for Reproductive Medicine disease scores. Postoperative pregnancy showed a significant protective effect on pain and disease recurrences. CONCLUSION(S): Prior surgery, presence of adhesions, and ovulation drugs are negative prognostic factors. Pregnancy has a protective effect on disease and pain recurrence.

Dermatol Online J. 2008 Oct 15;14(10):23.

Cutaneous umbilical endometriosis.

Lee A, Tran HT, Walters RF, Yee H, Rosenman K, Sanchez MR.

Department of Dermatology, New York University, USA.

A 35-year-old woman presented with a four-month history of a tender umbilical nodule that bleeds during her menstrual period. Physical examination showed a hyperpigmented umbilical nodule. A biopsy specimen showed fibrotic dermis with increased numbers of blood vessels and scattered glandular structures with areas of hemosiderin deposition consistent with a diagnosis of endometriosis. Cutaneous umbilical endometriosis is rare, with an estimated incidence of 0.5 to 1.0 percent. Although anti-gonadotropin medications, such as danazol, have been used for symptomatic control, but surgical excision is the treatment of choice owing to the possibility of malignant degeneration of cutaneous endometriosis.

Reprod Biol Endocrinol. 2008 Dec 2;6:59.

Serial analysis of gene expression reveals differential expression between endometriosis and normal endometrium. Possible roles for AXL and SHC1 in the pathogenesis of endometriosis.

Honda H, Barrueto FF, Gogusev J, Im DD, Morin PJ.

Laboratory of Cellular and Molecular Biology, National Institute on Aging, Baltimore MD 21224, USA. h-honda@qg8.so-net.ne.jp

BACKGROUND: Endometriosis is a clinical condition that affects up to 10% of the women of reproductive age. Endometriosis is characterized by the presence of endometrial tissues outside the uterine cavity and can lead to chronic pelvic pain, infertility and, in some cases, to ovarian cancer. METHODS: In order to better understand the pathogenesis of endometriosis, we have used Serial Analysis of Gene Expression (SAGE) to identify genes differentially in this disease by studying three endometriotic tissues and a normal endometrium sample. Promising candidates (AXL, SHC1, ACTN4, PI3KCA, p-AKT, p-mTOR, and p-ERK) were independently validated by immunohistochemistry in additional normal and endometriotic tissues. RESULTS: We identified several genes differentially expressed between endometriosis and normal endometrium. IGF2, ACTN4, AXL, and SHC1 were among the most upregulated genes. Comparison of the endometriosis gene expression profiles with the gene expression patterns observed in normal human tissues allowed the identification of endometriosis-specific genes, which included several members of the MMP family (MMP1,2,3,10,11,14). Immunohistochemical analysis of several candidates confirmed the SAGE findings, and suggested the involvement of the PI3K-Akt and MAPK signaling pathways in endometriosis. CONCLUSION: In human endometriosis, the PI3K-Akt and MAPK signaling pathways may be activated via overexpression of AXL and SHC1, respectively. These genes, as well as others identified as differentially expressed in this study, may be useful for the development of novel strategies for the detection and/or therapy of endometriosis.

Rom J Morphol Embryol. 2008;49(4):553-5.

Abdominal wall endometriosis: report of two cases.

Gourgiotis S, Veloudis G, Pallas N, Lagos P, Salemis NS, Villias C.

Second Surgical Department, 401 General Army Hospital of Athens, Greece. drsgourgiotis@tiscali.co.uk

Endometriosis is the abnormal existence of functional uterine mucosal tissue outside the uterus. It is a usual disorder of women in reproductive age, which is mainly located in the female genital tract. We report the cases of two women with endometriosis of the abdominal wall; the first one in the rectus abdominis muscle and the second one in the surgical scar of previous caesarian incision. The diagnosis was made by the histopathological analysis of the surgical specimens.

Reprod Sci. 2008 Nov;15(9):906-11.

Combination of CCR1 mRNA, MCP1, and CA125 measurements in peripheral blood as a diagnostic test for endometriosis.

Agic A, Djalali S, Wolfler MM, Halis G, Diedrich K, Hornung D.

Department of Gynecology and Obstetrics, University of Schleswig-Holstein, Luebeck, Germany.

This study investigated the possible use of CCR1 mRNA measurement in peripheral blood leukocytes in combination with measurements of monocyte chemotactic protein-1 (MCP-1) and CA125 protein in serum as a diagnostic test for endometriosis.The expression of CCR1 mRNA in peripheral blood leukocytes was measured by quantitative real-time polymerase chain reaction. MCP-1 and CA125 levels in serum were determined by ELISA and ECLIA.The ratio of CCR1/HPRT mRNA in peripheral blood of patients with endometriosis and adenomyosis was significantly elevated compared with women without endometriosis. Additionally, serum levels of MCP-1 and CA125 were significantly higher in patients with endometriosis. This method showed a sensitivity of 92.2%, a specificity of 81.6%, a negative predictive value of 83.3%, a positive predictive value of 92.3%, a likelihood ratio of a positive test result of 5.017, and a likelihood ratio of a negative test result of 0.096 to predict the presence or absence of endometriosis.The results imply the potential use of CCR1 mRNA, MCP-1, and CA125 protein measurements for the diagnosis or exclusion of endometriosis.

Expert Opin Emerg Drugs. 2008 Dec;13(4):547-71.

Emerging drugs for endometriosis.

Guo SW.

Shanghai Jiao Tong University School of Medicine, Renji Hospital, and Institute of Obstetric and Gynecologic Research, 145 Shandong Zhong Road, Shanghai 200001, China. hoxa10@gmail.com

BACKGROUND: Endometriosis is a benign, common gynecological disorder affecting mostly women of reproductive age. It is associated with dysmenorrhea, pelvic pain, and subfertility. The current non-surgical medical treatment is not satisfactory and there is a pressing need for novel therapeutics with better efficacy, tolerability and safety profiles. OBJECTIVE: To investigate the development of new therapies for endometriosis. METHODS: The PubMed database has been extensively searched for all compounds tested preclinically and clinically. RESULTS/CONCLUsion: Besides the three main classes of drugs, i.e., GnRH agonists, progestins, and androgenic agents, there are several classes of compounds that have been tested preclinically and clinically. Surprisingly, a considerable proportion of officially registered Phase II/III clinical trials are listed as completed yet no information on their outcomes is available. Three completed and published Phase II trials found the tested compound disappointing. Another two Phase II clinical trials have been suspended. This apparent gap between the generally promising preclinical findings and the clinical trial outcomes reflects our current woefully inadequate understanding of the mechanisms underlying endometriosis-associated pain and subferitility and recurrence of endometriosis; questions the adequacy and value of animal models of endometriosis that are still in use; highlights the difficulty in developing new therapeutics for endometriosis; and calls for more research in the mechanisms underlying endometriosis-associated pain and subferitility and recurrence of endometriosis.

BJOG. 2008 Dec;115(13):1721-2; author reply 1722.

Comment on:

BJOG. 2008 Jun;115(7):818-22.

Systematic review of the effects of aromatase inhibitors on pain associated with endometriosis.

El-Gizawy Z, Tzakas E, O’Brien PM.

BJOG. 2008 Dec;115(13):1715; author reply 1715-6.

Comment on:

BJOG. 2008 Aug;115(9):1159-64.

The use of JJ stent in the management of deep endometriosis lesion, affecting or potentially affecting the ureter: a review of our practice.

Ismail S.

BJOG. 2008 Dec;115(13):1611-5; discussion 1615.

Accident analysis: factors contributing to a ureteric injury during deep endometriosis surgery.

Schonman R, De Cicco C, Corona R, Soriano D, Koninckx PR.

Department of Obstetrics and Gynaecology, University Hospital, Leuven, Belgium. ronschonman@gmail.com

OBJECTIVE: To analyse factors associated with a ureteric injury. DESIGN: Retrospective accident analysis. SETTING: Deep endometriosis surgery in a tertiary referral centre. SAMPLE: Video recording of a surgical accident was analysed by six gynaecologists. METHODS: A 26-year-old woman underwent laparoscopy for deep endometriosis that involves the rectosigmoid and left ureter. Post operatively left ureter transection was identified and corrected by laparoscopy. Interventions were recorded and reviewed independently. MAIN OUTCOME MEASURES: Changes in surgical behaviour that could be measured were identified using the video recording. Results During the intervention, the periods of uncontrolled bleeding (P < 0.0001) and the duration of laser activation (P = 0.013) increased progressively. Simultaneous laser activation and bipolar coagulation only occurred at the end of surgery (seven episodes). Fatigue could not be measured. CONCLUSION: Unconscious acceleration of surgery, possibly as a consequence of fatigue, is suggested as a contributing factor for an error of judgement.

Zhonghua Fu Chan Ke Za Zhi. 2008 Jun;43(6):418-21.

[Expression of claudin-4 in eutopic and ectopic endometrium of women with endometriosis]

[Article in Chinese]

Pan XY, Weng ZP, Wang B.

Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan 250012, China. changpanxiaoyu@163.com

OBJECTIVE: To investigate the expression of claudin-4 in the eutopic and ectopic endometrium of women with endometriosis and evaluate the role of claudin-4 in the pathogenesis of endometriosis. METHODS: Thirty-five women with endometriosis and 35 controls were studied. Expression of claudin-4 was investigated using immunohistochemistry, western blot and RT-PCR, respectively. Morphologic change of tight junction was also observed in different kinds of endometria RESULTS: (1) Glandular epithelial cells of control endometrium and eutopic endometrium showed intact tight junctions in electron micrographs, whereas the morphology of tight junctions in ovarian endometriotic tissue was disrupted and collagen bundles could be easily detected. (2) The immunohistochemical staining of claudin-4 was localized to the glandular epithelial cell membrane. Deficient or weak staining was found in ovarian endometriotic tissues. In control endometrium, eutopic and ectopic endometrium of women with endometriosis, the expression of claudin-4 protein was 89 +/- 24, 84 +/- 22 and 27 +/- 14, respectively. Relative expression of claudin-4 mRNA was 14.5 +/- 6.8, 13.8 +/- 9.5 and 2.6 +/- 2.5, respectively. Expression of claudin-4 was significantly lower in the ectopic endometriotic tissue than in the eutopic endometrium and the control at both mRNA and protein levels (P<0.05). No significant difference was found between eutopic endometrium from women with endometriosis and control endometrium from women without endometriosis (P>0.05). CONCLUSION: Down-regulated expression of claudin-4 might play a pathogenic role in the formation of endometriosis.

Emerg Med J. 2008 Dec;25(12):859.

Catamenial pneumothorax.

Simpson A, Skelly E.

Accident and Emergency Department, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. antheasimpson@nhs.net

Pneumothorax is a potentially life-threatening condition caused by an accumulation of air or gas in the pleural space. This may occur either spontaneously or as a result of disease or injury. The term “catamenial” is derived from the Greek meaning “monthly”. Catamenial pneumothorax is a rare complication of endometriosis. A patient with a history of endometriosis presented to the accident and emergency department with increased abdominal pain, shortness of breath and wheeze. She was subsequently found to have a right-sided pneumothorax which was initially aspirated. However, the pneumothorax recurred and required chest drain insertion and admission to a medical ward. Further recovery was uneventful. It is important to maintain a high index of suspicion of catamenial pneumothorax in patients with a history of endometriosis.

APMIS. 2008 Sep;116(9):842-5.

Primary sex cord-like variant of endometrioid adenocarcinoma arising from endometriosis.

Kauppila S, Altinörs M, Väre P, Liakka A, Knuuti E, Nissi R.

Department of Pathology, Länsi-Pohja Central Hospital, Kemi, Finland.

Endometriosis, a relatively common disease generally affecting women in the reproductive age group, is mostly found in the pelvic organs. Although endometriosis is a benign disease, some malignant tumors have been reported to develop in endometriotic lesions, most commonly in the ovary. The relationship between endometriosis and malignancy is not well known, but the majority of endometriosis-associated ovarian malignancies are usually endometrioid adenocarcinomas and clear cell carcinomas. The sex cord-like variant of endometrioid adenocarcinoma is a rare tumor that histologically closely resembles the sex cord-stromal tumor. Despite its rarity, the correct histological diagnosis of the sex cord-like variant of endometrioid adenocarcinoma is crucial to avoid misdiagnosis of a less aggressive tumor. We here report a 53-year-old woman who was diagnosed as having this very rare subtype of endometroid adenocarcinoma curiously arising from an endometriotic lesion at the site of previous salpingo-oophorectomy. The tumor was diagnosed based on light microscopy and immunohistochemistry.

Fertil Steril. 2008 Nov;90(5 Suppl):S260-9.

Treatment of pelvic pain associated with endometriosis.

Practice Committee of American Society for Reproductive Medicine.

Pain associated with endometriosis requires careful evaluation to exclude other potential causes and may involve a number of different mechanisms. Both medical and surgical treatments for pain related to endometriosis are effective and choice of treatment must be individualized.

Fertil Steril. 2008 Nov 18. [Epub ahead of print]

Endometrial stromal cells from women with endometriosis reveal peculiar migratory behavior in response to ovarian steroids.

Gentilini D, Vigano P, Somigliana E, Vicentini LM, Vignali M, Busacca M, Di Blasio AM.

Molecular Biology Laboratory, Istituto Auxologico Italiano, Milan, Italy; Università degli Studi di Milano, Milan, Italy.

OBJECTIVE: To evaluate differences in endometrial stromal cell (ESC) migration between patients with and without endometriosis. DESIGN: Differences in ESC migration, cellular morphology, and cytoskeletal-actin dynamics were evaluated in response to platelet-derived growth factor-BB (PDGF-BB) and steroid hormones (17beta-estradiol and progesterone). SETTING: Medical school research laboratory. PATIENT(S): Endometrial biopsy samples obtained from 43 women: 23 as controls (endometriosis excluded by laparoscopy), 20 with severe or moderate endometriosis (diagnosed by laparoscopy). INTERVENTION(S): ESCs were treated with and without PDGF-BB, 17beta-estradiol, and progesterone. MAIN OUTCOME MEASURE(S): Cellular migration was evaluated by means of chemotaxis experiments in a Boyden chamber. Cellular morphology and cytoskeletal-actin dynamics were evaluated by immunofluorescence. RESULT(S): Progesterone stimulated the migratory behavior of ESCs derived from women with endometriosis, while 17beta-estradiol could stimulate motility of ESCs derived from both controls and women with endometriosis, with a greater effect observed in the latter group. No difference in ESC migratory behavior after PDGF-BB treatment was observed between women with and without the disease. Also, PDGF-BB and steroid hormones could modify the organization of actin cytoskeletal structures. CONCLUSION(S): Ovarian steroids differently affect the migration of ESCs derived from women with and without endometriosis. This effect is likely to involve cytoskeletal reorganization. Nongenomic signaling pathways induced by steroid hormones might have a role in this phenomenon.

Fertil Steril. 2008 Nov 18. [Epub ahead of print]

Endometrial stromal cells from women with endometriosis reveal peculiar migratory behavior in response to ovarian steroids.

Gentilini D, Vigano P, Somigliana E, Vicentini LM, Vignali M, Busacca M, Di Blasio AM.

Molecular Biology Laboratory, Istituto Auxologico Italiano, Milan, Italy; Università degli Studi di Milano, Milan, Italy.

OBJECTIVE: To evaluate differences in endometrial stromal cell (ESC) migration between patients with and without endometriosis. DESIGN: Differences in ESC migration, cellular morphology, and cytoskeletal-actin dynamics were evaluated in response to platelet-derived growth factor-BB (PDGF-BB) and steroid hormones (17beta-estradiol and progesterone). SETTING: Medical school research laboratory. PATIENT(S): Endometrial biopsy samples obtained from 43 women: 23 as controls (endometriosis excluded by laparoscopy), 20 with severe or moderate endometriosis (diagnosed by laparoscopy). INTERVENTION(S): ESCs were treated with and without PDGF-BB, 17beta-estradiol, and progesterone. MAIN OUTCOME MEASURE(S): Cellular migration was evaluated by means of chemotaxis experiments in a Boyden chamber. Cellular morphology and cytoskeletal-actin dynamics were evaluated by immunofluorescence. RESULT(S): Progesterone stimulated the migratory behavior of ESCs derived from women with endometriosis, while 17beta-estradiol could stimulate motility of ESCs derived from both controls and women with endometriosis, with a greater effect observed in the latter group. No difference in ESC migratory behavior after PDGF-BB treatment was observed between women with and without the disease. Also, PDGF-BB and steroid hormones could modify the organization of actin cytoskeletal structures. CONCLUSION(S): Ovarian steroids differently affect the migration of ESCs derived from women with and without endometriosis. This effect is likely to involve cytoskeletal reorganization. Nongenomic signaling pathways induced by steroid hormones might have a role in this phenomenon.

Fertil Steril. 2008 Nov 17. [Epub ahead of print]

Ectopic and eutopic stromal endometriotic cells have a damaged ceramide signaling pathway to apoptosis.

Chrobak A, Sieradzka U, Sozański R, Chełmońska-Soyta A, Gabryś M, Jerzak M.

Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland; Laboratory of Reproductive Immunology, Institute of Immunology and Experimental Therapy, Wroclaw Medical University, Wroclaw, Poland.

OBJECTIVE: To investigate whether sphingosine analogues, which activate the ceramide signaling pathway to apoptosis, can cause the death of ectopic (EEC) and eutopic stromal endometriotic cells (EEU), as well as healthy eutopic stromal endometrial cells (HEU). DESIGN: The EEC, EEU, and HEU isolated from fertile and infertile women with endometriosis were cultured for 48 hours in RPMI medium with 10% fetal calf serum (FCS) and with 2.5-10 muM sphingosine analogues. SETTING: A clinic for the treatment of endometriosis and basic research laboratories. PATIENT(S): Nineteen women with follicular cyst and 16 women with endometriosis. MAIN OUTCOME MEASURE(S): The percentage of proliferating cells was determined by 93-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) assay. Apoptosis and cell cycle were detected by fluorescence-activated cell sorter (FACS) Calibur flow cytometer. RESULT(S): The viability of EEC after exposure to 10 muM sphingosine analogues was 59.5% +/- 9.7% for D-sphingosine and 77.65 +/- 9.7% for DL-erythro-sphingosine, the viability of EEU was 69.2% +/- 14.2% and 42.0% +/- 15.5%, whereas the viability of comparative HEU was 9.0% +/- 4.8% and 18.8% +/- 8.3%, respectively. The differences were significant using the Mann-Whitney test. The apoptotic level of the cells treated with 10 muM sphingosine analogues for comparative HEU was 42.8% +/- 7.5% for D-sphingosine and 42.5% +/- 10.5% for DL-erythro-sphingosine, whereas for EEC this was 16.7% +/- 5.5% for D-sphingosine and 14.1% +/- 4.4% for DL-erythro-sphingosine and for EEU this was 14.3% +/- 4.7% and 22.9% +/- 8.9%, respectively. CONCLUSION(S): Ectopic and eutopic stromal endometrial cells from women with endometriosis have a damaged ceramide-downstream pathway to apoptosis.

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