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Int J Gynecol Pathol.2012 Jul;31(4):304-12.

The Dichotomy in the Histogenesis of Endometriosis-associated Ovarian Cancer: Clear Cell-type Versus Endometrioid-type Adenocarcinoma.

Kajihara H, Yamada Y, Shigetomi H, Higashiura Y, Kobayashi H.


Department of Obstetrics and Gynecology, Nara Medical University, Nara, Kashihara, Japan.


The histogenesis of endometriosis and endometriosis-associated ovarian cancer is one of the most mysterious aspects of pathology. To better understand the histogenesis of endometriosis and endometriosis-associated ovarian cancer, we analyzed the possibility of a link of endometrium, ovarian surface epithelium, and a cortical inclusion cyst to ovarian endometriosis and endometriosis-associated ovarian cancer by immunohistochemistry using the epithelial membrane antigen (an epithelial marker), calretinin (a mesothelial marker), and hepatocyte nuclear factor (HNF)-1β (a clear cell carcinoma-specific transcription factor). During ovarian surface epithelium invagination, cortical inclusion cyst epithelial cells may, in some cases, undergo mesothelial-epithelial transition and subsequently differentiate into endometriosis. This case of endometriosis that has undergone Müllerian metaplasia arises from the HNF-1β-negative cells. The remaining endometriosis may develop from the late secretory and menstrual endometria, with HNF-1β-positive staining, by retrograde menstruation. Endometrioid adenocarcinoma and clear cell carcinoma arise from the HNF-1β-negative and HNF-1β-positive epithelial cells of endometriosis, respectively. It has been proposed that clear cell and endometrioid-type adenocarcinomas arise from distinct types of endometriosis with different cells of origin.

Int J Gynecol Pathol.2012 Jul;31(4):297-303.

Endocervical-type Mucinous Borderline Tumors are Related to Endometrioid Tumors Based on Mutation and Loss of Expression of ARID1A.

Wu CH, Mao TL, Vang R, Ayhan A, Wang TL, Kurman RJ, Shih IM.


Departments of Pathology (C.H.W., R.V., R.J.K., I.M.S.) Gynecology and Obstetrics (C.H.W., R.V., T.L.W., R.J.K., I.M.S.), Johns Hopkins Medical Institutions, Baltimore, Maryland Department of Pathology (T.L.M.), National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan Department of Pathology (A.A.), Seirei Mikatahara General Hospital, Hamamatzu, Japan Department of Obstetrics and Gynecology (C.H.W.), Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.


Nongastrointestinal-type mucinous borderline tumors have been described as displaying endocervical and serous differentiation and hence have been termed “endocervical-type” mucinous borderline tumors, “mixed-epithelial papillary cystadenoma of borderline malignancy of mullerian type,” or “atypical proliferative seromucinous tumors.” A striking feature of these tumors is their frequent association with endometriosis, which has been reported in a third to a half of cases. This is an unusual finding, as pure endocervical and serous tumors are not usually associated with endometriosis. ARID1A is a recently identified tumor suppressor, which frequently loses its expression and is mutated in endometrium-related carcinomas including ovarian clear cell, ovarian endometrioid, and uterine endometrioid carcinomas. Although ARID1A mutations and their expression have been studied in gynecologic cancer, the expression pattern of ARID1A has not been investigated in ovarian atypical proliferative (borderline) tumors. In this study, we analyzed ARID1A expression in serous, gastrointestinal-type and endocervical-type (seromucinous) mucinous, and endometrioid atypical proliferative (borderline) tumors using immunohistochemistry and performed mutational analysis in selected cases. We observed loss of ARID1A staining in 8 (33%) of 24 seromucinous tumors. In contrast, ARID1A staining was retained in all the other 32 tumors except in 1 endometrioid tumor (P<0.01). Mutational analysis was performed on 2 representative seromucinous tumors, which showed complete loss of ARID1A. Both tumors harbored somatic inactivating ARID1A mutations. Previous studies have reported loss of expression and/or mutation of ARID1A in 30% to 57% of endometrioid and clear cell carcinomas but only rarely in serous tumors. In summary, these tumors often contain endocervical-type mucinous epithelium, but they typically display papillary architecture, unlike most endocervical neoplasms, and their immunophenotype is different from both endocervical and serous tumors. Moreover, they frequently contain ciliated cells, endometrial-type cells, cells with abundant eosinophilic cytoplasm, and hobnail-shaped cells, all of which can be found in endometrioid tumors. The loss of expression of ARID1A and the presence of inactivating mutations of the ARID1A gene further link this tumor to endometrioid and clear cell tumors, as does the frequent association with endometriosis. Accordingly, we suggest designating these tumors “atypical proliferative (borderline) papillary müllerian tumors” as this designation more accurately reflects their clinicopathologic, immunohistochemical, and molecular genetic features.

J Mol Neurosci.2012 Jul;47(3):495-504. Epub 2012 Mar 28.

Neurotrophin expression is not affected in uteri of women with adenomyosis.

Barcena de Arellano ML, Wagner MF, Oldeweme J, Arnold J, Ebert A, Schneider A, Mechsner S.


Endometriosis Research Centre Charité, Department of Gynaecology, Charité, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany.


To investigate the involvement of neurotrophins and nerve fibres in the pathogenesis of adenomyosis, we performed a retrospective, clinical study. Hysterectomy specimens from 40 patients with histologically proven adenomyosis and from 20 patients without adenomyosis or endometriosis were used for immunohistochemical analysis. In order to investigate neurotrophic properties in adenomyosis, the antibodies against nerve growth factor (NGF), neurotrophin 3 (NT-3), the high-affinity NGF receptor (TrkA), the low-affinity neurotrophin receptor (p75(NTR)), the neuronal marker S100 (for myelinated nerve fibres) and protein gene product 9.5 (PGP9.5; for intact nerve fibres) were used. There was no significant difference in the NGF, NT-3 and p75(NTR) expression in the myometrium or endometrium between the adenomyosis and the control group. The nerve fibre density (S100, PGP9.5 and p75(NTR)) did not significantly differ between the adenomyosis and control group, the nerve fibre density of the adenomyosis group was tendentially decreased when compared with the nonporous control group. The present study suggests that endometrial and uterine neurotrophin expression and endometrial innervation are not altered in adenomyosis; however, women with adenomyosis or with adenomyosis/endometriosis tendentially had less myometrial nerve fibres than the control group.

J Obstet Gynaecol.2012 Jul;32(5):498-9.

A massive haemorrhage caused by rupture of cystic cervical endometriosis.

Ye M, Huang L, Wang Y.


Department of Obstetrics and Gynecology, Guangzhou Women and Children Medical center, Guangzhou Medical College , Guangzhou, Guangdong , China.

Magn Reson Imaging.2012 Jul;30(6):860-8. Epub 2012 May 2.

Ultrasmall superparamagnetic iron oxides enhanced MR imaging in rats with experimentally induced endometriosis.

Lee HJ, Lee HJ, Lee JM, Chang Y, Woo ST.


Department of Gynecology, Daegu Fatima Hospital, Daegu, Republic of Korea.



The purpose of our study was to evaluate the feasibility of magnetic resonance imaging (MRI) using ultrasmall superparamagnetic iron oxides (USPIO) in the detection of experimentally induced endometriosis.


Endometriosis was surgically induced in rats by transplanting an autologous fragment of uterine tissue onto the inner surface of the abdominal wall, the posterior surface of the uterine body and the arterial cascades of the small intestines adjacent to mesenteric blood vessels. Six weeks later, MRI using Gd-DTPA and USPIO was performed for the evaluation of the ectopic uterine tissue (EUT). A scoring system was developed for image interpretation (0=absence, 1=probably absence, 2=probably presence and 3=presence). We defined MR index (MRIx) as the sum of T1-weighted and enhanced T1-weighted and T2-weighted image scores, and USPIO MRIx (MRIx(+USPIO)) as the MRIx score plus the score of USPIO-enhanced T2-weighted image.


The MRIx(+USPIO) was also higher in the successfully autotransplanted group than in the failed group (6.19±1.72 versus 3.94±1.20, P<.001). There was also a significant linear relationship between MRIx(+USPIO) and pathologic status (R(2)=0.494, P<.001). Thirty-one (64.6%) of the 48 implanted uterine tissues were histologically confirmed on pathologic review. The area of MRIx and MRIx(+USPIO) in the detection of EUT more than 3 mm in size was 0.739 and 0.913, respectively.


Our results suggest that USPIO-enhanced MRI could be a novel diagnostic tool for diagnosis in experimentally induced peritoneal endometriosis.

Maturitas.2012 Jul;72(3):214-9. Epub 2012 May 17.

Potential mechanisms of postmenopausal endometriosis.

Bendon CL, Becker CM.


Department of Plastic and Reconstructive Surgery, Oxford University Hospitals, Headley Way, Oxford, United Kingdom.


Endometriosis is a chronic gynaecological disorder, the cause of which remains a subject of controversy. Oestrogen dependence is considered central to development and progression, and endometriosis is widely viewed as a disease of the premenopausal years, which normally regresses during the menopause. Increasingly however, reports of cases of postmenopausal endometriosis challenge our current understanding of the pathophysiology and raise further questions concerning the processes involved. Exploring the limited evidence available on postmenopausal disease we attempt to draw comparisons with pre-menopausal endometriosis, and in doing so to propose mechanisms for postmenopausal disease that are compatible with our current general understanding of the condition.

Mol Hum Reprod.2012 Jul;18(7):372-7. Epub 2012 Jan 20.

Apolipoprotein E polymorphisms and spontaneous pregnancy loss in patients with endometriosis.

Collazo MS, Porrata-Doria T, Flores I, Acevedo SF.


Department of Physiology, Pharmacology, and Toxicology, Ponce School of Medicine and Health Sciences, PO Box 7004, Ponce, PR 00732, Puerto Rico.


Endometriosis affects >10% of women during their reproductive years, many of whom report high rates of spontaneous pregnancy loss (SPL). We examined whether gene polymorphisms in apolipoprotein E (APOE), which is involved in lipoprotein metabolism, are associated with endometriosis and/or endometriosis-associated infertility. We conducted a cross-sectional genetic association study of women surgically confirmed to have endometriosis (n = 345) and no surgical evidence of the disease (n = 266). Genotyping of APOE polymorphism (ε2, ε3, ε4) was conducted by polymerase chain reaction-restriction fragment length polymorphism followed by visualization of specific patterns by gel electrophoresis. Statistical significance of differences in genotype and allelic frequencies was assessed using Pearson’s χ(2) test and Risk analysis. Overall, we found no association between APOE genotype and diagnosis of endometriosis. However, patients with endometriosis who reported at least one SPL were three times more likely to be ε2 carriers and 2-fold less likely to be ε4 carriers. Compared with ε3 carriers, patients with endometriosis who were ε2 carriers and had at least one live birth reported four times the rate of SPL, while ε4 carriers were <0.4-fold less likely to report an SPL. Our data suggest that there may be an association between APOE allelic frequency and SPL in patients with endometriosis, which appears to be independent of mechanisms associated with infertility, an intriguing observation that deserves further investigation.

Respir Care.2012 Jul;57(7):1182-5. Epub 2012 Jan 23.

Catamenial pneumothorax due to bilateral pulmonary endometriosis.

Fang HY, Jan CI, Chen CK, Chen WT.


Department of Surgery, China Medical University Hospital, China Medical University, Taichung, Taiwan.


Co-existence of catamenial pneumothorax and hemoptysis is rare. We present a case of catamenial pneumothorax due to bilateral pulmonary endometriosis in a 45-year-old woman. The patient presented with a 3-year history of intermittent productive cough with blood-tinged sputum, chronic anemia, loss of appetite, and general weakness associated with menstruation. Three years prior to this presentation the patient had undergone a sigmoidectomy as treatment for endometriosis of the sigmoid colon with bleeding. Chest radiographs and computed tomography (CT) scan revealed multiple nodules in both lung parenchyma and recurrent pneumothorax. CT-guided biopsy revealed chronic inflammation of those pulmonary nodules, and laboratory studies disclosed elevated serum levels of carbohydrate antigen 19-9 (CA 19-9) and CA 125. Thoracoscopic wedge resection of the pulmonary nodules was performed, and histopathological examination of the resected nodules revealed endometriosis. At one-year follow-up there was no evidence of recurrence of gastrointestinal bleeding or pneumothorax.

Skeletal Radiol.2012 Jul;41(7):763-74. Epub 2012 Mar 13.

Sciatic nerve tumor and tumor-like lesions-uncommon pathologies.

Wadhwa V, Thakkar RS, Maragakis N, Höke A, Sumner CJ, Lloyd TE, Carrino JA, Belzberg AJ, Chhabra A.


The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA, vwadhwa1@jhmi.edu.


Sciatic nerve mass-like enlargement caused by peripheral nerve sheath tumors or neurocutaneous syndromes such as neurofibromatosis or schwannomatosis has been widely reported. Other causes of enlargement, such as from perineuroma, fibromatosis, neurolymphoma, amyloidosis, endometriosis, intraneural ganglion cyst, Charcot-Marie-Tooth disease, and chronic inflammatory demyelinating polyneuropathy are relatively rare. High-resolution magnetic resonance imaging (MRI) is an excellent non-invasive tool for the evaluation of such lesions. In this article, the authors discuss normal anatomy of the sciatic nerve and MRI findings of the above-mentioned lesions.

Surg Endosc.2012 Jul;26(7):2029-45. Epub 2012 Jan 26.

Nerve-sparing laparoscopic eradication of deep endometriosis with segmental rectal and parametrial resection: the Negrar method. A single-center, prospective, clinical trial.

Ceccaroni M, Clarizia R, Bruni F, D’Urso E, Gagliardi ML, Roviglione G, Minelli L, Ruffo G.


Division of Gynecologic Oncology, International School of Surgical Anatomy, Sacred Heart Hospital, “Ospedale Sacro Cuore-Don Calabria”, Via Don A.Sempreboni no. 5, 37024, Negrar, VR, Italy, issaschool@gmail.com.



The weight of surgical radicality, together with a lack of anatomical theoretical basis for surgery and inappropriate practical skills, can lead to serious impairments to bladder, rectal, and sexual functions after laparoscopic excision of deep infiltrating endometriosis. Although the “classical” laparoscopic technique for endometriosis excision involving segmental bowel resection has proven to relieve symptoms successfully, it is hampered by several postoperative long-term and/or definitive pelvic dysfunctions.


In this prospective cohort study, we compare the laparoscopic nerve-sparing approach to the classical laparoscopic procedure in a series of 126 cases. Satisfactory data for bowel, bladder, and sexual function were considered as primary endpoints.


A total of 126 patients were considered for analysis: 61 treated with nerve-sparing radical excision of pelvic endometriosis with segmental bowel resection (group B), and 65 treated with the classical technique (group A). Intraoperative, perioperative, and postoperative complications were similar between the two groups. Mean days of self-catheterization were significantly lower in the nerve-sparing group (39.8 days) compared with the non-nerve-sparing group (121.1 days; p < 0.001). The relapse rate within 12 months after surgery was comparable between the two groups. Patients of group A suffered from urinary retention more frequently between 1 and 6 months (p = 0.035) compared with group B and did not experience any improvement between 6 months and 1 year (p = 0.018). Overall detection of severe bladder/rectal/sexual dysfunctions was significantly different between the two groups, and 56 patients of group A (86.2%) reported a significantly higher rate of severe neurologic pelvic dysfunctions vs. 1 patient (1.6%) of group B (p < 0.001).


Our technique appears to be feasible and offers good results in terms of reduced bladder morbidity and apparently higher satisfaction than the classical technique. Considering that this kind of surgery requires uncommon surgical skills and anatomical knowledge, we believe that it should be performed only in selected reference centers.

Vet Pathol.2012 Jul;49(4):636-41. Epub 2011 Apr 26.

Pleural Endometriosis in an Aged Rhesus Macaque (Macaca mulatta): A Histopathologic and Immunohistochemical Study.

Assaf BT, Miller AD.


Harvard Medical School, New England Primate Research Center, One Pine Hill Drive, Southborough, MA 01772 Email: basel_assaf@hms.harvard.edu.


Endometriosis is defined as the presence of endometrial tissue outside the uterine cavity and is one of the most common reproductive abnormalities encountered in women as well as Old World primates. The majority of endometriosis cases in Old World primates occur within the abdominal cavity, with spread to extraabdominal sites considered to be a rare event. A 19-year-old multiparous female rhesus macaque (Macaca mulatta) presented to necropsy for difficulty breathing and weight loss. Grossly, the animal had marked abdominal endometriosis and severe hemoabdomen and hemothorax, the latter of which was accompanied by marked pleural fibrosis. Histologic examination confirmed the abdominal endometriosis and also revealed numerous uterine glands and stroma embedded within the pleural fibrosis. Rafts of endometrial tissue were present within pulmonary lymphatics and the tracheobronchial lymph nodes. Immunohistochemically, all ectopic endometrial tissue had varying degrees of positive immunoreactivity to cytokeratin, vimentin, progesterone and estrogen receptors, and calretinin but was negative for desmin and carcinoembryonic antigen. Pleural endometriosis is an extremely rare manifestation of endometriosis in nonhuman primates. This case report emphasizes lymphatic spread as a likely mechanism for extrauterine endometriosis.

Ultrasound Obstet Gynecol.2012 Jun 29. doi: 10.1002/uog.11216. [Epub ahead of print]

The reproducibility of the assessment of the severity of pelvic endometriosis using transvaginal ultrasound.

Holland TK, Hoo WL, Mavrelos D, Saridogan E, Cutner A, Jurkovic D.


Early Pregnancy and Gynaecology Assessment Unit, Department of Obstetrics and Gynaecology, Suite 8, Golden Jubilee Wing, King’s College Hospital, London, SE5 8RX, UK.


Objective To examine the reproducibility of assessment of severity of pelvic endometriosis by transvaginal ultrasound scan (TVS). Methods This was a prospective observational study from August 2006 to July 2009 conducted in two Academic Departments of Obstetrics and Gynaecology. All patients underwent a TVS performed by two ultrasound observers and a laparoscopic assessment of pelvic endometriosis. Each of the ultrasound observers was blinded to the results of the other observer. The reproducibility of TVS was examined by calculating the interobserver agreement between the observers for the American Society of Reproductive Medicine score and stage and the diagnosis of deeply infiltrating endometriosis (DIE). Results Thirty four patients were recruited to the study and had a TVS performed by both ultrasound operators. Of these patients, one did not have a laparoscopy and was therefore excluded from the final analysis. 12 (36.4%) patients had no endometriosis found, 1(3%) had minimal disease, 1 (3%) had mild disease, 5 (15.2%) had moderate disease and 14 (42.4%) had severe disease. The inter rater agreement was very good between examiner A and B (kappa = 0.931). The agreement between the TVS and laparoscopy findings was also very good (kappa = 0.955 and 0.966 for examiners A and B respectivley). The limits of agreement between observers A and B were -16.6 and 12.7. The mean difference was -1.9. Conclusion TVS is a reproducible method for the assessment of the severity of pelvic endometriosis.

Radiol Med.2012 Jun 28. [Epub ahead of print]

Deep pelvic endometriosis: accuracy of pelvic MRI completed by MR colonography.

Scardapane A, Lorusso F, Bettocchi S, Moschetta M, Fiume M, Vimercati A, Pepe ML, Angelelli G, Stabile Ianora AA.


Sezione di Diagnostica per Immagini, Di.M.I.M.P. – Centro interdipartimentale per lo studio dell’HHT, Azienda Universitario Ospedaliera Consorziale “Policlinico”, Università degli Studi di Bari, Bari, Italy, a.scardapane@radiologia.uniba.it.



This study assessed the diagnostic accuracy of pelvic magnetic resonance (MR) imaging completed by MR colonography for the preoperative evaluation of deep pelvic endometriosis in patients undergoing laparoscopic surgery.


A total of 143 patients (mean age 34.3±5.1 years) with a clinical suspicion of deep pelvic endometriosis were assessed by pelvic MR and MR colonography. All patients underwent laparoscopic surgery 3-10 weeks after the MR examination. The presence, location, number and extent of endometriotic lesions were evaluated. Data obtained with MR were compared with surgical findings. MR sensitivity, specificity, positive (PPV) and negative (NPV) predictive values and diagnostic accuracy values were calculated for each site by considering the laparoscopic and histological findings as the reference standard.


Laparoscopy confirmed the presence of endometriosis in 119/143 patients (83%); in 76/119 (64%) deep pelvic endometriosis was diagnosed, whereas in the remaining 43/119 (36%), superficial peritoneal implants and endometriomas were found. In 32/119 (27%) patients, intestinal lesions were detected. MR had sensitivity, specificity, PPV, NPV and diagnostic accuracy values of 67-100%, 85-100%, 83-100%, 84-100% and 84-100%, respectively, in recognising lesions located in different pelvic sites. CONSLUCIONS: MR imaging combined with colonography is a highly accurate tool for characterising deep endometriotic lesions in patients scheduled for laparoscopic surgery. In particular, MR colonography has very high accuracy in detecting colorectal involvement.

Virchows Arch.2012 Jun 27. [Epub ahead of print]

Intestinal metaplasia and colonization of endometriosis in a case of an appendiceal mucinous neoplasm.

Libbrecht L, Snauwaert C, De Vos M, Geboes K, Cuvelier C, Ferdinande L.


Department of Pathology, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium.

Hum Reprod.2012 Jun 26. [Epub ahead of print]

Evaluation of a panel of 28 biomarkers for the non-invasive diagnosis of endometriosis.

Vodolazkaia A, El-Aalamat Y, Popovic D, Mihalyi A, Bossuyt X, Kyama CM, Fassbender A, Bokor A, Schols D, Huskens D, Meuleman C, Peeraer K, Tomassetti C, Gevaert O, Waelkens E, Kasran A, De Moor B, D’Hooghe TM.


Leuven University Fertility Centre, Department of Obstetrics and Gynaecology, University Hospital Gasthuisberg, Leuven, Belgium.


BackgroundAt present, the only way to conclusively diagnose endometriosis is laparoscopic inspection, preferably with histological confirmation. This contributes to the delay in the diagnosis of endometriosis which is 6-11 years. So far non-invasive diagnostic approaches such as ultrasound (US), MRI or blood tests do not have sufficient diagnostic power. Our aim was to develop and validate a non-invasive diagnostic test with a high sensitivity (80% or more) for symptomatic endometriosis patients, without US evidence of endometriosis, since this is the group most in need of a non-invasive test.MethodsA total of 28 inflammatory and non-inflammatory plasma biomarkers were measured in 353 EDTA plasma samples collected at surgery from 121 controls without endometriosis at laparoscopy and from 232 women with endometriosis (minimal-mild n = 148; moderate-severe n = 84), including 175 women without preoperative US evidence of endometriosis. Surgery was done during menstrual (n = 83), follicular (n = 135) and luteal (n = 135) phases of the menstrual cycle. For analysis, the data were randomly divided into an independent training (n = 235) and a test (n = 118) data set. Statistical analysis was done using univariate and multivariate (logistic regression and least squares support vector machines (LS-SVM) approaches in training- and test data set separately to validate our findings.ResultsIn the training set, two models of four biomarkers (Model 1: annexin V, VEGF, CA-125 and glycodelin; Model 2: annexin V, VEGF, CA-125 and sICAM-1) analysed in plasma, obtained during the menstrual phase, could predict US-negative endometriosis with a high sensitivity (81-90%) and an acceptable specificity (68-81%). The same two models predicted US-negative endometriosis in the independent validation test set with a high sensitivity (82%) and an acceptable specificity (63-75%).ConclusionsIn plasma samples obtained during menstruation, multivariate analysis of four biomarkers (annexin V, VEGF, CA-125 and sICAM-1/or glycodelin) enabled the diagnosis of endometriosis undetectable by US with a sensitivity of 81-90% and a specificity of 63-81% in independent training- and test data set. The next step is to apply these models for preoperative prediction of endometriosis in an independent set of patients with infertility and/or pain without US evidence of endometriosis, scheduled for laparoscopy.

Mol Cell Endocrinol.2012 Jun 24;357(1-2):108-18. Epub 2011 Nov 17.

The progesterone receptor regulates implantation, decidualization, and glandular development via a complex paracrine signaling network.

Wetendorf M, DeMayo FJ.


Interdepartmental Program in Cell & Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA. wetendor@bcm.edu


Many women are affected by infertility and reproductive-associated disease such as endometriosis or endometrial cancer. Successful pregnancy is dependent on a healthy uterus that is fit to receive and support a fertilized embryo. The uterus is an endocrine organ, responsive to the presence of the ovarian steroid hormones, estrogen and progesterone, which activate transcription of target genes through the binding of their cognate receptors, the estrogen receptor and the progesterone receptor. Progesterone signaling has been demonstrated to be critical for the initiation and continuance of pregnancy. Through the induction of Ihh, Wnt, and Bmp pathways within the epithelial and stromal compartments of the uterus, embryo attachment and implantation occur followed by decidualization of the surrounding stroma. Furthermore, these pathways have been shown to be involved in uterine glandular development. This review highlights the integral role of uterine progesterone-mediated paracrine signaling in gland development and pregnancy.

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