Mol Med Rep. 2018 Mar 29. doi: 10.3892/mmr.2018.8823. [Epub ahead of print] Zearalenone regulates endometrial stromal…
J Minim Invasive Gynecol. 2015 Sep-Oct;22(6):1059-67.
Colorectal Endometriosis Responsible for Bowel Occlusion or Subocclusion in Women With Pregnancy Intention: Is the Policy of Primary in Vitro Fertilization Always Safe?
Roman H1, Puscasiu L2, Lempicki M3, Huet E4, Chati R4, Bridoux V4, Tuech JJ4, Abo C5.
To discuss the risk of bowel occlusion or subocclusion in patients with pregnancy wish and deep colorectal endometriosis, when surgery is postponed until after conception.
A prospective series of consecutive patients managed for occlusion or subocclusion between January 2012 and January 2015 (Canadian Task Force classification II-2). Deep endometriosis had previously been diagnosed in all patients; however, they were advised to postpone surgery until after conception.
University tertiary referral center.
Twelve women with bowel occlusion or subocclusion due to deep endometriosis and desiring pregnancy.
Surgical management including colorectal resection.
MAIN OUTCOME MEASURES:
Digestive symptoms, including standardized gastrointestinal questionnaires and preoperative imaging assessment of deep endometriosis.
The patients enrolled in the series represent 5% of 241 patients with colorectal endometriosismanaged over 37 consecutive months. Major digestive complaints were bloating, defecation pain, constipation, liquid stools, and a feeling of incomplete stool evacuation. The median length of digestive tract stenosis was 50 mm (range, 20-100 mm). In 8 patients (67%), computed tomography-based virtual colonoscopy revealed a virtual digestive lumen. The median length of colorectal specimen removed was 120 mm (range, 60-200 mm). Three patients (25%) had Clavien-Dindo IIIb and IVa postoperative complications with favorable outcomes within up to 20 days after surgery.
Given the risk of bowel occlusion or subocclusion in young patients with colorectal endometriosis, an exhaustive assessment of deep disease and advice at a tertiary referral center appears to be mandatory before prioritizing primary in vitro fertilization instead of primary surgery.
Reprod Sci. 2015 Dec;22(12):1549-60.
Activation of the MAPK/ERK Cell-Signaling Pathway in Uterine Smooth Muscle Cells of Women With Adenomyosis.
Streuli I1, Santulli P2, Chouzenoux S3, Chapron C4, Batteux F5.
We investigated whether the myometrium might be intrinsically different in women with adenomyosis. We studied whether the mitogen-activated protein kinases/extracellular signal-regulated kinases (MAPKs/ERKs) and phosphoinositide 3-kinase/mammalian target of rapamycin/AKT (PI3K/mTOR/AKT) cell-signaling pathways, implicated in the pathogenesis of endometriosis, might also be activated in uterine smooth muscle cells (uSMCs) of women with adenomyosis and measured the production of reactive oxygen species (ROS), proinflammatory mediators that modulate cell proliferation and have been shown to activate the MAPK/ERK pathway in endometriosis. The uSMC cultures were derived from myometrium biopsies obtained during hysterectomy or myomectomy in women with adenomyosis and controls with leiomyoma. Proliferation of uSMCs and in vitro activation of the MAPK/ERK cell-signaling pathway were increased in women with adenomyosis compared to controls. The activation of the PI3K/mTOR/AKT pathway was not significant. The ROS production and ROS detoxification pathways were not different between uSMCs of women with adenomyosis and controls suggesting an ROS-independent activation of the MAPK/ERK pathway. Our results also provide evidence that protein kinase inhibitors and the rapanalogue temsirolimus can control proliferation of uSMCs in vitro suggesting an implication of the MAPK/ERK and the PI3K/mTOR/AKT pathways in proliferation of uSMCs in women with adenomyosis and leiomyomas.
Am J Pathol. 2015 Aug;185(8):2286-97.
Estradiol is a critical mediator of macrophage-nerve cross talk in peritoneal endometriosis.
Greaves E1, Temp J2, Esnal-Zufiurre A3, Mechsner S4, Horne AW3, Saunders PT3.
Endometriosis occurs in approximately 10% of women and is associated with persistent pelvic pain. It is defined by the presence of endometrial tissue (lesions) outside the uterus, most commonly on the peritoneum. Peripheral neuroinflammation, a process characterized by the infiltration of nerve fibers and macrophages into lesions, plays a pivotal role in endometriosis-associated pain. Our objective was to determine the role of estradiol (E2) in regulating the interaction between macrophages and nerves in peritoneal endometriosis. By using human tissues and a mouse model of endometriosis, we demonstrate that macrophages in lesions recovered from women and mice are immunopositive for estrogen receptor β, with up to 20% being estrogen receptor α positive. In mice, treatment with E2 increased the number of macrophages in lesions as well as concentrations of mRNAs encoded by Csf1, Nt3, and the tyrosine kinase neurotrophin receptor, TrkB. By using in vitro models, we determined that the treatment of rat dorsal root ganglia neurons with E2 increased mRNA concentrations of the chemokine C-C motif ligand 2 that stimulated migration of colony-stimulating factor 1-differentiated macrophages. Conversely, incubation of colony-stimulating factor 1 macrophages with E2 increased concentrations of brain-derived neurotrophic factor and neurotrophin 3, which stimulated neurite outgrowth from ganglia explants. In summary, we demonstrate a key role for E2 in stimulating macrophage-nerve interactions, providing novel evidence that endometriosis is an estrogen-dependent neuroinflammatory disorder.
Peptides. 2015 Oct;72:34-43.
Peptides: Basic determinants of reproductive functions.
Celik O1, Aydin S2, Celik N3, Yilmaz M4.
Mammalian reproduction is a costly process in terms of energy consumption. The critical information regarding metabolic status is signaled to the hypothalamus mainly through peripheral peptides from the adipose tissue and gastrointestinal tract. Changes in energy stores produce fluctuations in leptin, insulin, ghrelin and glucose signals that feedback mainly to the hypothalamus to regulate metabolism and fertility. In near future, possible effects of the nutritional status on GnRH regulation can be evaluated by measuring serum or tissue levels of leptin and ghrelin in patiens suffering from infertility. The fact that leptin and ghrelin are antagonistic in their effects on GnRH neurons, their respective agonistic and antagonistic roles make them ideal candidates to use instead of GnRH agonist and antagonist. Similarly, kisspeptin expressing neurons are likely to mediate the well-established link between energy balance and reproductive functions. Exogenous kisspeptin can be used for physiological ovarian hyperstimulation for in-vitro fertilization. Moreover, kisspeptin antagonist therapy can be used for the treatment of postmenapousal women, precocious puberty, PCOS, endometriosis and uterine fibroids. In this review, we will analyze the central mechanisms involved in the integration of metabolic information and their contribution to the control of the reproductive function. Particular attention will be paid to summarize the participation of leptin, kisspeptin, ghrelin, NPY, orexin, urocortin, VIP, insulin, galanin, galanin like peptide, oxytocin, agouti gene-related peptide, and POMC neurons in this process and their possible interactions to contribute to the metabolic control of reproduction.
Biomed Rep. 2015 Mar;3(2):220-224.
Involvement of vascular endothelial growth factor -460 C/T, +405 G/C and +936 C/T polymorphisms in the development of endometriosis.
Szczepańska M1, Mostowska A2, Wirstlein P3, Skrzypczak J1, Jagodziłski PP2.
There are inconsistent data on the contribution of vascular endothelial growth factor (VEGF) -460 C/T (rs833061), +405 G/C (rs2010963) and +936 C/T (rs3025039) single-nucleotide polymorphisms (SNPs) to endometriosis in different ethnicities. Therefore, using high-resolution melting curve analysis, the present study examined the distribution of these SNPs in females with endometriosis-related infertility and a control group. None of the three VEGF SNPs were associated with endometriosis-related infertility in the dominant and recessive models. The lowest P-values of the trend were observed for the VEGF +936 C/T (rs3025039) SNP in endometriosis-related infertility (Ptrend =0.149). Similarly, haplotype analyses of VEGF SNPs did not demonstrate any SNP combination as a risk for endometriosis-related infertility, and the lowest overall P-values, P=0.141 and Pcorr =0.395, were observed for a haplotype (TGT) of the above SNPs. Taken together, these results did not demonstrate the contribution of VEGF C/T, +405 G/C and +936 C/T SNPs to endometriosis-related infertility.
Case Rep Obstet Gynecol. 2015
Ovarian Seromucinous Borderline Tumor and Clear Cell Carcinoma: An Unusual Combination.
Nakamura E1, Sato Y2, Moriguchi S2, Yamashita A1, Higo T3, Asada Y1.
Ovarian seromucinous borderline tumors (SMBTs) are rare. They architecturally resemble serous borderline tumors but are much more frequently associated with endometriosis. The coexistence of other tumors with seromucinous tumors is also extremely rare. Here, we report an unusual combination of bilateral ovarian SMBT and clear cell carcinoma associated with polypoid endometriosis of the colon, in a 62-year-old woman. There was no transitional lesion between the two tumors. Immunohistochemistry showed different staining patterns in tumor components. Seromucinous tumor cells were positive for estrogen receptor (ER) and progesterone receptor (PgR) but negative for Napsin A, p504S, and HNF1B. Clear cell tumor cells were positive for Napsin A and p504S and focally positive for HNF1B but negative for ER and PgR. Loss of ARID1A expression was not observed in SMBTs, clear cell tumors, or endometriosis. These findings suggest that these tumors arose from separate endometriosis foci and collided within the same ovary. To the best of our knowledge, this is the first case of this unusual combination of ovarian seromucinous tumor and clear cell carcinoma to be reported in the English literature.
Gynecol Oncol Rep. 2014 Nov 20;11:13-5.
Endometrial stromal nodule of the vaginal wall with a review of vulvovaginal endometrial stromal neoplasms.
Sánchez-Ferrer ML1, Ferri-Ñíguez B2, Schuldt M3, Nogales FF3.
- It is reported the first endometrial stromal nodule (ESN) in the vagina.•This is an excepcionall ESN because it was not associated with endometriosis•It was successfully treated by local resection.•Primary vulvovaginal endometrial stromal neoplasms are rare (only 5 reported).
Zhonghua Fu Chan Ke Za Zhi. 2015 Apr;50(4):291-5.
Effect of bazedoxifene on endometriosis in a rat model.
Lyu H1, Liu Y2, Dang Q1, Chen H1, Chen R1.
To investigate the therapeutic mechanism of bazedoxifene, the third-generation selective ER modulator (SERM), on endometriosis lesions in a rat model.
Endometriosis was induced by transplanting pieces of endometrium from other syngeneic rats that were as donors onto the subcutaneous of other unmated female rats. The rats with successful ectopic implants were divided into two groups: control group (n=10) and bazedoxifene group (n=10). The macroscopic morphology, volume, histopathology of ectopic implant and rats uterine wet weight were determined before and after the treatment. Expression of proliferation cell nuclear antigen (PCNA), ER and PR in the eutopic endometrium and endometriosis lesions detected by immunohistochemistry in the two groups.
(1) The gross morphology and histological changes of endometriosis lesions in rats after treatment: compared with the control group, it was obviously depauperated and had more less glands and blood vessels in the stroma. (2) The change of rats’ weight, the volume of endometriosis lesion before and after treatment and rats uterine wet weigh after treatment respectively in the control group and the bazedoxifene group: rats’ weight were respectively before treatment: (201±17) g, (202±18) g, that were respectively after treatment: (266±16) g, (261±16) g, which showed no significant difference between two groups before and after treatment (P>0.05). The volume of ectopic implant before treatment were respectively (85±17) mm3, (85±12) mm3, and showed no significant difference between two groups; that were respectively (48±11) mm3, (24±9) mm3 afte rtreatment, which was significantly decreased compared with the control group (P<0.05). Rats uterine wet weight after treatment were respectively: (0.77±0.16) g, (0.45±0.18) g, and was significantly reduced compared with the control group (P<0.05). (3) The protein expression levels of PCNA, ER and PR in the endometriosis lesions after treatment were respectively 0.282±0.044, 0.51±0.06, 0.49±0.05 in the control group, 0.191±0.020, 0.23±0.03, 0.48±0.06 in the bazedoxifene group; that in eutopic endometrium were respectively 0.369±0.081, 0.56±0.08, 0.56±0.10 in the control group, 0.211±0.037, 0.27±0.05, 0.54±0.08 in the bazedoxifene group; the protein expression levels of PCNA and ER in endometriosis lesions and the eutopic endometrium were significantly decreased in the bazedoxifene group compared with the control group (P<0.05), but the protein levels of PR in endometriosis lesionsand and the eutopic endometrium were not significantly altered by treatment (P>0.05).
Bazedoxifene could obviously reduce the size of endometriosis lesions, the mechanism may be related with suppressing estrogen-induced proliferation, the expression of ER and direct ER antagonism by this SERM.
Acta Vet Scand. 2015 Jun 18;57:31.
A rare case of endometrioma in a bitch.
Paiva BH1, Silva JF2, Ocarino NM3, Oliveira CA4, Assis WA5, Serakides R6.
Endometriosis is ectopic development of endometrial glands and stroma in extra-uterine sites and if the lesions occur as a well-defined mass is referred to as endometrioma. In the literature, endometrioma has been reported in only women and there are no reports of endometrioma in animals, including non-human primates.
A rare case of endometrioma is reported in an 11-year-old female German Shepherd with clinical signs of dehydration, anemia and prostration. Necropsy revealed ascites, generalized pallor, and a well-demarcated reddish mass adjacent to the left ovary and uterus and adherent to the retroperitoneum. The mass measured 25.0 × 20.0 cm with intermingled soft and firm areas. Upon incision, the mass was found to be solid with variable sized cystic cavities filled with coagulated blood. Microscopically, the mass was composed of cuboidal or prismatic epithelial cells arranged in tubules or acini. The epithelium of the mass had similar characteristics to the normal endometrium with PAS-positive secretions. The stroma was prominent and formed by loose connective tissue and smooth muscle fibers as confirmed by Masson trichrome. Extensive multifocal areas of hemorrhage were also observed in the stroma of the mass and in the interior of some epithelium-lined, cystic structures. Most of the epithelial cells had strong and diffuse cytokeratin expression, and some had vimentin expression. Epithelial and stromal cells also showed ERβ, AR, VEGF and COX2 expression. The stroma showed areas with strong and diffuse vimentin expression. Factor VIII expression was observed only in the endothelium of blood vessels in the stroma.
Acta Obstet Gynecol Scand. 2015 Sep;94(9):954-9.
Intestinal surgery performed by gynecologists.
Martínez-Serrano MJ1, Martínez-Román S1, Pahisa J1, Balasch J1, Carmona F1.
Our objective was to compare the feasibility and safety of surgical procedures to treat gynecological pathologies with intestinal involvement performed by skilled gynecological surgeons and by a multidisciplinary team of gynecologists plus colorectal surgeons.
MATERIAL AND METHODS:
We performed a comparative, observational, prospective study at a tertiary referral center. The population included all women undergoing bowel surgery for gynecological pathologies over a 3-year period. Cases were analyzed by the specialty of the main surgeon performing the intestinal procedure. The main outcome measures were surgical procedure characteristics and postoperative outcomes and complications.
A total of 65 women were included. Surgery was exclusively performed by a subspecialized gynecologist in 30.8% of the women, and undertaken by a multidisciplinary team (colorectal surgeons and gynecologists) in 69.2%. The main demographic and clinical characteristics were comparable in both groups. Main indications for bowel resection in gynecological surgery were advanced ovarian cancer and deep infiltrating endometriosis. In addition to the standard gynecological surgical procedures, a total of 135 intestinal segments were resected, with sigmoid colon the most frequent intestinal segment resected in both groups (53% in the gynecologist group and in 60% in the multidisciplinary group). No significant differences were observed between the two groups in the distribution and frequency of surgical techniques used, rate of complications, mean hospitalization time or frequency of re-intervention.
Skilled gynecological surgeons appear to be equally good at handling common intestinal problems as a team of gynecologist and colorectal surgeons.
Contraception. 2015 Aug;92(2):116-9.
Endometriosis-induced changes in regulatory T cells – insights towards developing permanent contraception.
Fazleabas AT1, Braundmeier A2, Parkin K3.
Endometriosis is a gynecological disorder that is associated with alterations in the immune system that contributes to its pathology as well as its associated infertility.
This brief report summarizes our findings related to the changes in T regulatory cells (Tregs) that may affect the uterine environment and impact the fertility of women and nonhuman primates with endometriosis.
Targeted therapies that could reduce Tregs within the reproductive tract may have a potential as long-lasting or permanent contraception.
Gynecol Obstet Invest. 2015;80(2):85-8.
DNA repair gene XRCC1 and XRCC4 variations and risk of endometriosis: an association study.
Saliminejad K1, Saket M, Kamali K, Memariani T, Khorram Khorshid HR.
Endometriosis is a polygenic and multifactorial disease. DNA damage plays a major role in mutagenesis, carcinogenesis and aging and is usually repaired by the action of several DNA repair enzymes. We investigated the association of the common variations of the DNA repair genes XRCC1 and XRCC4 with susceptibility to endometriosis in an Iranian population.
In total, 160 patients with endometriosis (stages I-IV) and 174 healthy women were included in this case-control study. Genotyping of XRCC1 codon 399 as well as of XRCC4 -1394T/G, codon 247 and intron 3 insertion/deletion variations was performed using restriction fragment length polymorphism analysis of PCR-amplified fragments.
The XRCC4 -1394TG genotype frequency was significantly lower (p = 0.005) in the patients (9.4%) than in the controls (21.1%). The frequency of the -1394G allele was significantly lower (p < 0.0001) in the patients (6.6%) than in the controls (19.0%). There were no statistically significant differences in the genotype and allele frequencies of the XRCC1 codon 399, XRCC4 codon 247 and XRCC4 intron 3 insertion/deletion polymorphisms between the cases and controls.
The XRCC4 -1394T/G polymorphism was associated with susceptibility to endometriosis in an Iranian population.
Curr Rheumatol Rev. 2015;11(2):146-66.
Central and peripheral pain generators in women with chronic pelvic pain: patient centered assessment and treatment.
Women with chronic pelvic pain (CPP) often present without obvious cause on imaging studies, laboratory values or physical exam. Dysfunctional sensory processing in the central nervous system (CNS) may explain pain of unclear origin. Central sensitization (CS), a mechanism of centrally mediated pain, describes this abnormal processing of sensory information. Women with CPP often present with several seemingly unrelated symptoms. This can be explained by co-existing chronic pain syndromes occurring in the same patient. Central sensitization occurs in all of these pain syndromes, also described as dysfunctional pain syndromes, and thus may explain why several often occur in the same patient. Six of the most common pain disorders that co-exist in CPP include endometriosis, painful bladder syndrome/interstitial cysitis, vulvodynia, myofascial pain/ pelvic floor hypertonus, irritable bowel syndrome, and primary dysmenorrhea. Central pain generators, (pain originating from CS) and peripheral pain generators, (pain from local tissue damage), can both occur in each of these six conditions. These pain generators will be described. Chronic pain, specifically dysfunctional sensory processing, is recognized as a systemic disease process like diabetes to be managed as opposed to a local problem to be “fixed” or cured. A multi-disciplinary approach to assessment and treatment with a focus on improving emotional, physical and social functioning instead of focusing strictly on pain reduction is more effective in decreasing disability. This is best achieved by determining the patient’s needs and perspective through a patient-centered approach. Algorithms for such an approach to assessment and treatment are outlined.
EMBO Mol Med. 2015 Aug;7(8):996-1003.
H19 lncRNA alters stromal cell growth via IGF signaling in the endometrium of women with endometriosis.
Ghazal S1, McKinnon B2, Zhou J3, Mueller M4, Men Y5, Yang L6, Mueller M2, Flannery C1, Huang Y7, Taylor HS7.
Endometriosis affects approximately 15% of reproductive aged women and is associated with chronic pelvic pain and infertility. However, the molecular mechanisms by which endometriosis impacts fertility are poorly understood. The developmentally regulated, imprinted H19 long noncoding RNA (lncRNA) functions to reduce the bioavailability of microRNA let-7 by acting as a molecular sponge. Here we report that H19 expression is significantly decreased in the eutopic endometrium of women with endometriosis as compared to normal controls. We show that decreased H19 increases let-7 activity, which in turn inhibits Igf1r expression at the post-transcriptional level, thereby contributing to reduced proliferation of endometrial stromal cells. We propose that perturbation of this newly identified H19/Let-7/IGF1R regulatory pathway may contribute to impaired endometrial preparation and receptivity for pregnancy in women with endometriosis. Our finding represents the first example of a lncRNA-based mechanism in endometriosis and its associated infertility, thus holding potential in the development of novel therapeutics for women with endometriosis and infertility.
Int J Womens Health. 2015 Jun 11;7:595-603.
Endometriosis: alternative methods of medical treatment.
Muñoz-Hernando L1, Muñoz-Gonzalez JL1, Marqueta-Marques L1, Alvarez-Conejo C1, Tejerizo-García Á1, Lopez-Gonzalez G1, Villegas-Muñoz E2, Martin-Jimenez A3, Jiménez-López JS1.
Endometriosis is an inflammatory estrogen-dependent disease defined by the presence of endometrial glands and stroma at extrauterine sites. The main purpose of endometriosis management is alleviating pain associated to the disease. This can be achieved surgically or medically, although in most women a combination of both treatments is required. Long-term medical treatment is usually needed in most women. Unfortunately, in most cases, pain symptoms recur between 6 months and 12 months once treatment is stopped. The authors conducted a literature search for English original articles, related to new medical treatments of endometriosis in humans, including articles published in PubMed, Medline, and the Cochrane Library. Keywords included “endometriosis” matched with “medical treatment”, “new treatment”, “GnRH antagonists”, “Aromatase inhibitors”, “selective progesterone receptor modulators”, “anti-TNF α”, and “anti-angiogenic factors”. Hormonal treatments currently available are effective in the relief of pain associated to endometriosis. Among new hormonal drugs, association to aromatase inhibitors could be effective in the treatment of women who do not respond to conventional therapies. GnRH antagonists are expected to be as effective as GnRH agonists, but with easier administration (oral). There is a need to find effective treatments that do not block the ovarian function. For this purpose, antiangiogenic factors could be important components of endometriosis therapy in the future. Upcoming researches and controlled clinical trials should focus on these drugs.
Eur J Obstet Gynecol Reprod Biol. 2015 Aug;191:68-71.
Evaluation of YB-1 levels in patients with endometriosis.
Ahrens T1, Silveira CG2, Banz-Jansen C3, Rody A3, Hornung D4.
The objective of this study is the evaluation of serum YB-1 levels in the diagnosis of endometriosis.
Serum samples of 12 patients with histologically confirmed endometriosis and of 10 control patients were collected. Western blot analysis was used to assess serum YB-1 levels. Groups were compared with Student’s t-test or, if not normally distributed, with the Mann-Whitney test. Sensitivity and specificity for the potential diagnostic performance of serum YB-1 were assessed by receiver operating characteristic (ROC) curves.
Serum YB-1 levels were significantly higher in patients with endometriosis (=0.004). The area under the curve was 0.867 (95% confidence interval 0.714-1.019) with sensitivity and specificity of 83.3% and 70% respectively.
Serum YB-1 levels in patients with endometriosis are significantly higher compared to control patients and may be used as a potential diagnostic biomarker for endometriosis.
Respir Med. 2015 Oct;109(10):1235-43.
Focal pleural tumorlike conditions: nodules and masses beyond mesotheliomas and metastasis.
de Paula MC1, Escuissato DL2, Belém LC3, Zanetti G4, Souza AS Jr5, Hochhegger B6, Nobre LF7, Marchiori E8.
A tumorlike condition of the pleura is any nonmalignant lesion of the pleura or within the pleural space that could be confused with a pleural tumor on initial imaging. Tumorlike conditions of the pleura are relatively rare compared with neoplastic lesions such as mesotheliomas and metastases. Imaging-based diagnosis of these conditions can be difficult due to the similarity of appearance. Thus, recognition of certain imaging patterns and interpretation of these patterns in the clinical context are important. Pleural endometriosis, thoracic splenosis, thoracolithiasis, foreign bodies, pleural pseudotumors and pleural plaques are significant examples of focal tumorlike conditions discussed in this article. Computed tomography is the mainstay imaging technique for the primary assessment of pleural disease, but other imaging methods, such as magnetic resonance imaging and positron-emission tomography, can be of great support in the diagnosis.
Ann Agric Environ Med. 2015;22(2):259-64
Impact of heavy metals on the female reproductive system.
Rzymski P1, Tomczyk K2, Rzymski P2, Poniedziałek B1, Opala T2, Wilczak M3.
It has been recognized that environmental pollution can affect the quality of health of the human population. Heavy metals are among the group of highly emitted contaminants and their adverse effect of living organisms has been widely studied in recent decades. Lifestyle and quality of the ambient environment are among these factors which can mainly contribute to the heavy metals exposure in humans.
A review of literature linking heavy metals and the female reproductive system and description of the possible associations with emission and exposure of heavy metals and impairments of female reproductive system according to current knowledge.
The potential health disorders caused by chronic or acute heavy metals toxicity include immunodeficiency, osteoporosis, neurodegeneration and organ failures. Potential linkages of heavy metals concentration found in different human organs and blood with oestrogen-dependent diseases such as breast cancer, endometrial cancer, endometriosis and spontaneous abortions, as well as pre-term deliveries, stillbirths and hypotrophy, have also been reported.
Environmental deterioration can lead to the elevated risk of human exposure to heavy metals, and consequently, health implications including disturbances in reproduction. It is therefore important to continue the investigations on metal-induced mechanisms of fertility impairment on the genetic, epigenetic and biochemical level.
Ann Agric Environ Med. 2015;22(2):329-31.
Effectiveness of laparoscopic surgeries in treating infertility related to endometriosis.
Słabuszewska-Jóźwiak A1, Ciebiera M1, Baran A1, Jakiel G1.
Endometriosis is defined as an illness caused by the presence of foci of endometrial tissue outside the uterine cavity. The illness is found in 5-10% of women at reproductive age. In the group of those suffering from endometriosis, the percentage of infertile women amounts to 50%. At higher stages of endometriosis clinical advancement, the suggested treatment is the application of assisted reproductive technology.
The aim of the study was assessment of the effectiveness of laparoscopy in treating infertility related to endometriosis among women treated in our clinic in 2009-2012.
MATERIALS AND METHOD:
The clinic is a medical centre focused on advanced minimally invasive surgical treatment, especially laparoscopic surgeries in diseases of the uterus – with a focus on laparoscopic surgeries for patients with endometriosis of the recto-vaginal area. 53 female patients treated for infertility who underwent a laparoscopic surgical procedure to remove the foci of endometriosis in 2009-2012, were analysed retrospectively. After the surgical procedure, the patients were observed over a period of 12 months, during which the frequency of pregnancies (including natural and assisted pregnancies) was assessed in relation to the stage of endometriosis advancement (rAFS).
In 17 out of 53 (32%) patients who underwent the surgical procedure a clinical pregnancy was diagnosed. 11 out of 53 (20.75%) women became pregnant spontaneously, 6 out of 53 (11.32%) patients became pregnant as a result of assisted reproductive technology (ART) (5 IVF and 1 IUI). The average time from the date of surgical procedure to spontaneous pregnancy amounted to 6 months.
Laparoscopy is a vital therapeutic method. Operative laparoscopy is an efficient method for treating infertility related to endometriosis, and the procedure seems to be the most effective particularly at stage III rAFS. The period for expectant management after a surgical procedure should last 6 months.
Ann Agric Environ Med. 2015;22(2):353-6
Pharmacological treatment and regional anesthesia techniques for pain management after completion of both conservative and surgical treatment of endometriosis and pelvic adhesions in women with chronic pelvic pain as a mandated treatment strategy.
Malec-Milewska M1, Horosz B1, Sękowska A1, Kolęda I1, Kosson D2, Jakiel G3.
Chronic pelvic pain syndrome occurs in 4-14% of women. Pain pathomechanism in this syndrome is complex, as it is common to observe the features of nociceptive, inflammatory, neuropathic and psychogenic pain. The common findings in women with pelvic pain are endometriosis and pelvic adhesions.
Aim of the study was to test the effectiveness of pharmacological treatment and regional anesthesia techniques for pain control as the next step of treatment after the lack of clinical results of surgical and pharmacological methods normally used in the management of endometriosis and pelvic adhesions.
MATERIALS AND METHOD:
18 women were treated between January 2010 – October 2013 in the Pain Clinic of the Department of Anaesthesiology and Intensive Care at the Centre for Postgraduate Education in Warsaw due to chronic pelvic pain syndrome related to either endometriosis or pelvic adhesions. During the previous step of management, both conservative and surgical treatments were completed without achieving satisfactory results. Initial constant pain severity was 3-9 points on the Numeric Rating Scale, while the reported paroxysmal pain level was 7-10. The pharmacological treatment implemented was based on oral gabapentinoids and antidepressants, aided by neurolytic block of ganglion of Walther, pudendal nerve blocks and topical treatment (5% lidocaine, 10% amitriptyline, 10% gabapentin).
In 17 women, a significant reduction of both constant and paroxysmal pain was achieved, of which complete and permanent cessation of pain occurred in 6 cases. One patient experienced no improvement in the severity of her symptoms.
The combination of pain management with pharmacological treatment, pudendal nerve blocks, neurolysis of ganglion impar (Walther) and topical preparations in cases of chronic pelvic pain syndrome seems to be adequate medical conduct after failed or otherwise ineffective causative therapy.
Histopathology. 2016 Feb;68(3):398-404.
Clinicopathological and immunohistological features of polypoid endometriosis.
Stewart CJ1,2, Bharat C3,4.
To compare clinicopathological and immunohistochemical features of polypoid endometriosis (PE) and non-polypoid endometriosis (NPE).
METHODS AND RESULTS:
Fifteen cases of PE and 20 cases of NPE were assessed. All cases were stained immunohistochemically for CD10 and p16 and the proportion of p16-positive stromal and epithelial cells was estimated. On review, 10 PE cases resembled NPE histologically but occurred at mucosal or serosal surfaces, or within cyst cavities, that permitted polyp formation. These cases had a similar age distribution and immunohistochemical profile to NPE. The remaining five PE cases showed histological similarity to eutopic endometrial polyps; these occurred in older patients, and showed significantly greater stromal and epithelial p16 immunoreactivity.
There are two main subgroups of PE. The majority of cases in this series showed similar histological features to NPE, but involved anatomical sites that facilitated exophytic or polypoid growth. The remaining PE cases resembled eutopic endometrial polyps histologically and immunophenotypically and they occurred in older patients. These findings suggest that such lesions are ‘true’ polyps sharing a pathogenetic relationship with similar lesions arising in the endometrium.
Niger J Clin Pract. 2015 Sep-Oct;18(5):577-83.
The association between endometriosis and survival outcomes of ovarian cancer: Evidence-based on a meta-analysis.
Yang B1, Wang D, Chen H, Yang F.
Although it is generally recognized that endometriosis was significantly associated with higher risk of ovarian cancer, the association between endometriosis and the cancer survival outcomes is still not clear. This meta-analysis aims to pool previous studies and to make an update estimate.
Relevant studies were searched among PubMed, Medline and Embase. Hazard ratio (HR) and the corresponding 95% confidence intervals (CI) of progression-free survival (PFS) and overall survival (OS) were pooled with generic inverse variance method. The proportion of the low stage and grade tumors (stage: Stage I and II among total; grade: Grade I among total) in endometriosis-associated ovarian cancer (EAOC) group and in non-EAOC group were assessed with odd ratio and the corresponding 95% CI.
Endometriosis-associated ovarian cancer were significantly associated with higher rate of OS in crude analysis (HR: 0.74, 95% CI: 0.63-0.87, P = 0.0003). However, in most of the studies included, the OS benefit was not significant under multivariable survival analysis. EAOC patients generally had early-stage, low histological grade tumors and younger age compared with non-EAOC patients. No difference was observed in PFS between the two groups.
The OS benefits associated with endometriosis might be closely related to higher prevalence of patients diagnosed at early-stage and greater chance of receiving optimal cytoreductive surgery or chemotherapy. Endometriosis should not be viewed as an independent prognostic factor of ovarian cancer.
Geburtshilfe Frauenheilkd. 2015 May;75(5):462-469.
Supporting and Inhibiting Factors When Coping with Endometriosis From the Patients’ Perspective.
Kundu S1, Wildgrube J2, Schippert C1, Hillemanns P1, Brandes I1.
Aim: Endometriosis is a chronic gynaecological disorder with manifold symptoms and psychosocial effects on the lives of affected women. The prevalence of endometriosis is estimated to be up to ten percent of women of reproductive age. As a result of its unclear aetiology, only limited treatment options are available. The treatment and care of affected women is therefore a challenge for their doctors. There is a need for healthcare services to provide affected women with support to cope with the disorder better. The aim of the study was to identify supporting and inhibiting factors on disease management to develop new support ideas. Materials and Methods: The results are based on a content analysis evaluation of text responses from 135 women with confirmed endometriosis. Open questions about disease management were posed in a patient questionnaire. A classification system was developed according to Mayrings Qualitative Content Analysis, which allowed the main topics to be identified and summarised qualitatively using a quantitative intermediate step. Results: Social support, treatment, as well as professional and healthcare system performance were found to be particularly supportive by patients. However, when questioned about inhibiting factors, healthcare system professionals and their performance were most commonly criticised. Just over 50 % of women expressed their criticism of doctors. Quality of care and empathy towards the patients were especially criticised. There is also a need for improvement with regard to communication and general support from doctors. The results illustrate the importance of doctors for women affected by endometriosis, but make it clear that there is a great need for improvement with regard to the profession. Conclusion: The results provide the first indication of problem areas in the management of endometriosis from which approaches could be developed to improve care. However, it must be pointed out that the perspective of affected women was solely investigated. For a comprehensive analysis, it would be necessary to include the perspective of care providers and the influence of society as well as the healthcare system.
World J Nucl Med. 2015 May-Aug;14(2):131-3.
Retroperitoneal Endometriosis: A Possible Cause of False Positive Finding at (18)F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.
Maffione AM1, Panzavolta R2, Lisato LC3, Ballotta M3, D’Isanto MZ2, Rubello D1.
Endometriosis is a frequent and clinically relevant problem in young women. Laparoscopy is still the gold standard for the diagnosis of endometriosis, but frequently both morphologic and functional imaging techniques are involved in the diagnostic course before achieving a conclusive diagnosis. We present a case of a patient affected by infiltrating retroperitoneal endometriosis falsely interpreted as a malignant mass by contrast-enhanced magnetic resonance imaging and (18)F-fluorodeoxyglucose positron emission tomography/computed tomography.
Arch Gynecol Obstet. 2015 Oct;292(4):707-8.
Cecal volvulus caused by endometriosis in a young woman.
Ito D1, Kaneko S2, Morita K3, Seiichiro S4, Teruya M5, Kaminishi M6.
Cecal volvulus is relatively rare. Moreover, to the best of our knowledge, a case of cecal volvulus caused by endometriosis has not yet been reported.
A 41-year-old woman was admitted to our hospital with a 14-day history of subacute intermittent right lower quadrant abdominal pain. Simple abdominal radiography and abdominal computed tomography findings were suggestive of sigmoid volvulus, and she underwent an emergency colonoscopy. Following colonoscopic reduction, the patient’s symptoms resolved quickly, and elective laparoscopic surgery was scheduled 2 weeks after admission. Intraoperative examination revealed a significantly distended cecum and ascending colon, which was twisted around a short rope-like adhesion that connected the cecum and the mesentery of the transverse colon, whereas the sigmoid colon was neither twisted nor extended. We laparoscopically performed an ileocecal resection. The postsurgery histopathological examination revealed the presence of endometrial tissue in the short rope-like adhesion. This finding confirmed that cecal volvulus in this patient was caused by endometriosis.
Cecal volvulus should be considered in relatively young women who present with atypical right lower abdominal pain. Whenever possible, secondary factors should be evaluated preoperatively, especially in relatively young patients.
J Assist Reprod Genet. 2015 Jul;32(7):1135-44
Meta-analysis of the association of AhR Arg554Lys, AhRR Pro185Ala, and ARNT Val189Val polymorphisms and endometriosis risk in Asians.
Zheng NN1, Bi YP, Zheng Y, Zheng RH.
Several studies have suggested an association between the polymorphisms AhR Arg554Lys, AhRR Pro185Ala, and ARNT Val189Val and endometriosis, but results have been inconclusive. The aim of the present study was to assess these associations by meta-analysis.
Eligible literatures were retrieved from PubMed, ISI Web of Science, Elsevier Science Direct, and several Chinese databases. The pooled odds ratios (ORs) and the corresponding 95 % confidence intervals (CIs) were calculated with a random or fixed-effect model.
A total of six eligible studies were included. Regarding the AhR Arg554Lys and ARNT Val189Val polymorphisms, no obvious associations were found in either overall analysis or subgroup analysis based on the country, source of control, sample size, and genotyping method. For the AhRR Pro185Ala polymorphism, overall results suggested a marginal association with endometriosis susceptibility under the dominant model (OR = 1.65, 95 % CI = 1.00-2.72). Furthermore, a significantly increased risk for endometriosis was found in the subgroups which used the TaqMan method for genotype analysis or had a sample size ≥200.
This meta-analysis suggested that the polymorphisms of AhR Arg554Lys and ARNT Val189Val are not associated with endometriosis, while the AhRR Pro185Ala polymorphism may be associated with endometriosis risk. However, further case-control studies with larger sample sizes are needed to confirm our results.
Am J Reprod Immunol. 2015 Oct;74(4):291-301.
Natural Killer Cells: Key Players in Endometriosis.
Thiruchelvam U1, Wingfield M2,3, O’Farrelly C1,4.
Endometriosis affects more than 10% of women, causing significant pain and morbidity. It is also a significant cause of infertility. The aetiology of the disease remains an enigma, and the mechanisms responsible for the associated infertility are unclear. A role for immune cells in endometriosis has been postulated, with attention directed towards natural killer (NK) cells and macrophages. NK cells kill tumours and infected cells but also have roles in tissue remodelling in several organs including the uterus and are key to successful pregnancy. Here, we explore evidence (from peer-reviewed published articles) of phenotypic and functional abnormalities in NK cell subpopulations of women with endometriosis. It is clear that peripheral blood NK cells and peritoneal NK cells have reduced cytotoxic function in women with endometriosis. Uterine NK cells have a vital role in infertility, but very little research has been carried out in this area. We propose that abnormal u NK cell activity may contribute to the pathogenesis of endometriosis and its associated infertility and that future research should focus on this complex area.
J Med Case Rep. 2015 Jun 26;9:150.
Endometriosis with an acute colon obstruction: a case report.
Baden DN1, van de Ven A2, Verbeek PC3.
The presentation of an acute bowel obstruction caused by endometriosis in an emergency department setting is rare, as it usually presents through years of complaints in the absence of a distinct acute onset. In this report, we present a case of a patient who was familiar with abdominal complaints and eventually required emergency surgery to treat an acute bowel obstruction caused by endometriosis. Endometrioses present infrequently in the acute phase, and only a few cases in which emergency surgery was required have been described in the literature.
A 31-year-old Caucasian woman presented to the emergency room of our hospital with a distended abdomen, pain and nausea accompanied by a history of 14 years of chronic abdominal pain and constipation. An abdominal X-ray and subsequent computed tomographic scan showed a severely distended cecum of 9cm with stenosis in the sigmoid. Cecal blow-out was considered highly likely, and, during an emergency laparotomy, an obstructing process was found in the sigmoid. An oncologic resection of the sigmoid was performed with a primary anastomosis and loop ileostomy. A pathological examination revealed a tumor of 4cm in the sigmoid, which contained a tubelike structure with cytogenic stroma and the remains of focal bleeding. These are typical aspects of endometriosis.
Infiltrating endometriosis is an invalidating disease that can be misdiagnosed for a wide range of other diseases. Emergency room physicians and surgeons should be aware that it can present as an acute obstruction and should be considered in diagnosing women of childbearing age. After initial colonoscopy, emergency surgery is the best therapeutic approach if there is a complete obstruction.
Arch Gynecol Obstet. 2015 Dec;292(6):1393-9.
Impact of endometriosis on quality of life, anxiety, and depression: an Austrian perspective.
Friedl F1, Riedl D2, Fessler S1, Wildt L3, Walter M1, Richter R4, Schüßler G2, Böttcher B5.
Several studies on the quality of life in patients with endometriosis have been performed with conflicting results. This cross-section survey examines the influence of endometriosis on the psychological well-being and the quality of life and the incidence of anxiety and depression among these patients, recruited from a tertiary care center in Austria.
Three standardized questionnaires of 62 patients with endometriosis were evaluated: status of health questionnaire (SF-36), hospital anxiety and depression scale (HADS-D), and endometriosis health profile (EHP-30). Quality of life status (EHP-30) was compared with published samples of the Oxford hospital and the Charite Berlin. Chi-square tests, independent sample t-tests, and one-way independent ANCOVA’s were used to compare SF- 36 and HADS- D scores to 61 healthy controls. Pearson product-moment-correlation coefficients were used to investigate correlations between symptoms of depression and anxiety in the patient sample.
Moderate to severe anxiety symptoms were found in 29 %; depressive symptoms were present in 14.5 % of the patients. Both symptoms occurred in 12.9 %. We found significant better values in all subscales of the EHP compared to the Oxford and Berlin samples. The control sample showed significant better subjective general health (p < 0.001), vitality (p < 0.001), mental health (p < 0.001), and better emotional role functioning (p < 0.001). Participants age significantly influenced mental health and emotional role functioning.
The impact of endometriosis on life quality in our study was considerably less than in other studies but equivalent to other chronic medical conditions. It could be shown that endometriosis is influenced by biopsychosocial variables. However, the elevated presence of anxiety and depressive symptoms indicates the need of psychosomatic treatment of affective disorders to prevent manifestation.
Rozhl Chir. 2015 May;94(5):211-5.
Endometriosis of the appendix presenting like acute appendicitis-a case report.
Černá M, Novák P, Třeška V, Mukenšnabl P, Hudec A.
In general, pain in the lower right abdomen is the most frequent reason for hospital surgical admissions, acute appendicitis representing the most common cause of operation for acute abdomen. Timely appendectomy remains the only treatment in the early stages of inflammation and is usually uncomplicated, requiring only a short hospital stay. A differential diagnostic analysis necessitates a search for other, particularly long-term symptoms that might be driven to the background in cases of acute exacerbation.
The case report presents a 38-year-old female patient who was admitted for lower right abdominal pain. Clinical examination and a blood test both suggested typical acute uncomplicated appendicitis, and therefore the patient underwent appendectomy. Haemorrhagic peritoneal fluid and nodularity of the appendix not typical for appendicitis was found. Oedema of the terminal ileum and a right adnexal tumour were a surprising finding. A more extensive surgical procedure involving ileocaecal resection and right-side adnexectomy was finally performed with regard to the intraoperative finding. The definitive diagnosis of appendiceal endometriosis, endometrial mass in the terminal intestine and ovarian endometriosis was established by histological evaluation. Long-term follow-up revealed microadenocarcinoma of cervix uteri.
It is generally very difficult to confirm appendiceal endometriosis before operation, and revealing primary appendiceal endometriosis is virtually impossible. It is advisable to consider endometriosis in fertile women with chronic abdominal pain of unclear aetiology and gynaecological symptoms in their personal history. The best diagnostic and therapeutic method, respectively, is laparoscopy enabling exploration of the entire peritoneal cavity including the minor pelvis, and performing appendectomy as well as excision of suspicious endometrial lesions. The definitive diagnosis is usually established by histopathological evaluation. Gynaecological assessment and follow-up is highly recommended after surgery.
Syst Biol Reprod Med. 2015;61(5):263-76.
Follicular fluid alterations in endometriosis: label-free proteomics by MS(E) as a functional tool for endometriosis.
Regiani T1, Cordeiro FB1, da Costa Ldo V1, Salgueiro J2, Cardozo K2, Carvalho VM2, Perkel KJ3, Zylbersztejn DS1, Cedenho AP1, Lo Turco EG1.
Endometriosis is a chronic gynecological condition that affects 10-32% of women of reproductive age and may lead to infertility. The study of protein profiles in follicular fluid may assist in elucidating possible biomarkers related to this disease. For this, follicular fluid samples were obtained from women with tubal factor or minimal male factor infertility who had pregnancy outcomes after in vitro fertilization (IVF) treatment (control group, n = 10), women with endometriosis (endometriosis group, n = 10), along with the endometrioma from these same patients were included (endometrioma group, n = 10). For proteomic analysis, samples were pooled according to their respective groups and normalized to protein content. Proteins were analyzed by in tandem mass spectrometry (MS(E)) Spectra processing and the ProteinLynx Global Server v.2.5. was used for database searching. Data was submitted to the biological network analysis using Cytoscape 2.8.2 with ClueGO plugin. As a result, 535 proteins were identified among all groups. The control group differentially or uniquely expressed 33 (6%) proteins and equal expression of 98 (18%) proteins was observed in the control and endometriosis groups of which 41 (7%) proteins were further identified and/or quantified. Six (1%) proteins were observed in both the endometriosis and endometrioma groups, but 212 (39%) proteins were exclusively identified and/or quantified in the endometrioma group. There were 9 (1%) proteins observed in both the control and endometrioma groups and there were 139 (25%) proteins common among all three groups. Distinct differences among the protein profiles in the follicular fluid of patients included in this study were found, identifying proteins related to the disease progression and IVF success. Thus, some pathways related to endometriosis are associated with the presence of specific proteins, as well as the absence of others. This study provides a first step to the development of more sensitive diagnostic tests and treatment.
Eur J Obstet Gynecol Reprod Biol. 2015 Aug;191:116-20.
Effects of low dose oral contraceptive pill containing drospirenone/ethinylestradiol in patients with endometrioma.
Taniguchi F1, Enatsu A2, Ota I3, Toda T4, Arata K5, Harada T5.
Low dose oral contraceptive pills (OCPs) that contain synthetic estrogen and progestin are often used to relieve chronic pelvic pain associated with endometriosis. We sought to evaluate the efficacy of drospirenone/ethinylestradiol (DRSP/EE) with low-dose estrogen in treating endometrioma.
A prospective clinical study in six hospitals and one clinic in Japan was conducted. Forty-nine 23- to 45-year-old patients who suffered from endometriosis-associated dysmenorrhea were included in the study. The primary endpoint was the change in size of ovarian endometrioma as measured by transvaginal ultrasonography. The secondary endpoint was the change in dysmenorrhea as evaluated by VAS (visual analog scale) scores before treatment and at 3 and 6 cycles of treatment. In addition, serum CA125, anti-mullerian hormone (AMH), interleukin (IL)-6, and IL-8 were evaluated after 6 cycles of treatment.
The maximum diameter and volume of the ovarian endometrioma significantly decreased after 3 and 6 cycles compared with pretreatment. VAS scores of dysmenorrhea pain were also reduced after 1, 3 and 6 cycles. A significant correlation between the reduced size of the endometrioma and the decline of VAS scores was found. The levels of serum CA125 and AMH concentration were decreased after 6 cycles. No significant changes were observed in serum IL-6 and IL-8.
Low dose DRSP/EE therapy is a promising treatment not only to reduce the size of endometrioma but also for dysmenorrhea.
Mol Cell Endocrinol. 2015 Sep 15;413:61-5
Metformin regulates stromal-epithelial cells communication via Wnt2/β-catenin signaling in endometriosis.
Zhang H1, Xue J1, Li M1, Zhao X1, Wei D1, Li C2.
In previous studies, we found that endometriotic stromal cells lose the ability to regulate cell survival signaling in endometriotic epithelial cells. Here, we invested the effect of Metformin on the stromal-epithelial cells crosstalk in endometriosis and explored the pathway that might be involved. We found that ectopic endometriotic stromal cells (ESC) expressed and secreted higher Wnt2 protein compared with normal endometrial stromal cells (NSC). Conditioned medium (CM) from ESC supplemented with Wnt2 antibody significantly inhibited the growth of normal endometrial epithelial cells (NEC), while CM from ESC per se showed no significant effect on the growth of NEC. Metformin decreased the expression and secretion of Wnt2 in ESC. CM from Metformin-pretreated ESC significantly inhibited the growth of NEC. In conclusion, Wnt2/β-catenin signaling was involved in stromal-epithelial cells interaction in endometriosis. Metformin might regulate the stroma-epithelium communication via Wnt2-mediated signaling in endometriosis.
J Endometr Pelvic Pain Disord. 2015 Jul-Sep;7(3):89-114.
Impact of physical activity on pain perception in an animal model of endometriosis.
Hernandez S1, Cruz ML1, Torres-Reveron A2, Appleyard CB1.
Symptoms of endometriosis, such as pain and infertility, are considered significant sources of stress. In many chronic conditions, exercise can act as a stress buffer and influence pain perception. We tested the impact of swimming exercise on pain perception and pain receptors in an animal model of endometriosis.
Endometriosis (Endo) was induced in female rats by suturing uterine horn tissue next to the intestinal mesentery. Sham rats received sutures only. Rats were exposed to swimming exercise for 7 consecutive days, while no-exercise rats were left in the home cage. Fecal pellets were counted after swimming as an index of anxiety, and serum corticosterone levels measured. Pain perception was assessed using the hot plate test for hyperalgesia and Von Frey test for allodynia. Mu-opioid receptor (MOR) and neurokinin-1 receptor expression in the spinal cord was measured by immunofluorescence.
Fecal pellet counts were higher in those animals that swam (p<0.05), but no significant difference in corticosterone was found. Although Endo-exercise rats had higher colonic damage (p<0.05) with more cellular infiltration, the lesions were smaller than in Endo-no exercise rats (p<0.05). Exercise did not ameliorate the hyperalgesia, whereas it improved allodynia in both groups. MOR expression was significantly higher in Endo-exercise vs. Endo-no exercise rats (p<0.01), similar to Sham-no exercise levels.
Our results point toward beneficial effects of swimming exercise during endometriosisprogression. Physical interventions might be investigated further for their ability to reduce perceived stress and improve outcomes in endometriosis.
Am J Epidemiol. 2015 Jul 15;182(2):148-56
A prospective study of insulin-like growth factor 1, its binding protein 3, and risk of endometriosis.
Mu F, Hankinson SE, Schernhammer E, Pollak MN, Missmer SA.
Several retrospective case-control studies suggested that insulin-like growth factor 1 (IGF-1) or insulin-like growth factor binding protein 3 (IGFBP-3) was associated with endometriosis. However, results are inconsistent and no prospective study exists. We prospectively evaluated associations between plasma levels of IGF-1 and IGFBP-3 and laparoscopically confirmed endometriosis in a case-control study nested within the Nurses’ Health Study II. Between blood collections in 1996-1999 and 2007, we ascertained 310 premenopausal women with incident endometriosis and 615 matched controls. We estimated incidence rate ratios and 95% confidence intervals using multivariable conditional logistic regression. We observed no statistically significant associations between endometriosis and IGF-1 (incidence rate ratio (IRR) = 0.88, 95% confidence interval (CI): 0.61, 1.27; Ptrend = 0.48), IGFBP-3 (IRR = 1.12, 95% CI: 0.80, 1.57; Ptrend = 0.51), and the IGF-1:IGFBP-3 molar ratio (IRR = 0.94, 95% CI: 0.66, 1.34; Ptrend = 0.64), comparing the top with the bottom tertile. IGF-1, IGFBP-3, and the molar ratio appeared to be positively associated with endometriosis risk among women aged <40 years at blood draw (IGF-1: IRR = 1.60, 95% CI: 0.86, 2.98; IGFBP-3: IRR = 1.85, 95% CI: 1.08, 3.16; IGF-1:IGFBP-3: IRR = 1.57, 95% CI: 0.85, 2.88) but not among women aged ≥40 years at blood draw (all Pheterogeneity ≤ 0.05). Overall, these data suggest that, if IGF-1 or IGFBP-3 plays a role in the etiology of endometriosis, it is minimal and perhaps only among younger women.
Iran J Basic Med Sci. 2015 May;18(5):423-9.
Systematic enrichment analysis of microRNA expression profiling studies in endometriosis.
The purpose of this study was to conduct a meta-analysis on human microRNAs (miRNAs) expression data of endometriosis tissue profiles versus those of normal controls and to identify novel putative diagnostic markers.
MATERIALS AND METHODS:
PubMed, Embase, Web of Science, Ovid Medline were used to search for endometriosis miRNA expression profiling studies of endometriosis. The miRNAs expression data were extracted, and study quality of each article was assessed. The frequently reported miRNAs with consistent regulation were screened out by a meta-profiling algorithm. The putative targets of consistently expressed miRNAs were predicted by using four target prediction tools (TargetScan, PicTar, miRanda, miRDB), and gene ontology pathway enrichment analysis (KEGG and Panther pathways) of the miRNA targets were carried out with GeneCodis web tool.
A total of 194 related literatures were retrieved in four databases. One hundred and thirty four differentially expressed miRNAs were found in the 12 microRNA expression profiling studies that compared endometriosis tissues with normal tissues, with 28 miRNAs reported in at least two studies, and 9882 candidate genes retrieved for 13 consistently expressed miRNAs. Kyoto encyclopedia of genes and genomes (KEGG) and Panther pathways enrichment analysis showed that endometriosis related differently expressed miRNA targets were mainly enriched in cancer, endocytosis, Wnt signalling pathway, and angiogenesis. It showed that these differently expressed miRNAs and gene are potential biomarkers of endometriosis.
miRNAs appear to be potent regulators of gene expression in endometriosis and its associated reproductive disorders, raising the prospect of using miRNAs as biomarkers and therapeutic agent in endometriosis.
Eur Rev Med Pharmacol Sci. 2015;19(11):1964-72.
Environment and Endometriosis: a toxic relationship.
Soave I1, Caserta D, Wenger JM, Dessole S, Perino A, Marci R.
Endometriosis is a common, benign, estrogen-dependent gynecological disease that represents one of the main causes of hospitalization in industrialized countries. It is well established that a large amount of natural and man-made chemicals are present in the environment and both humans and animals are exposed to them. Dioxin and dioxin-like compounds have long biological half-life, can accumulate within the organism and could negatively affect several physiological processes. The purpose of this review is to provide an overview of the possible relationship between these chemicals and the pathogenesis of endometriosis.
Curr Opin Obstet Gynecol. 2015 Aug;27(4):284-90.
Preoperative assessment and diagnosis of endometriosis: are we any closer?
PURPOSE OF REVIEW:
The management of endometriosis has progressed vastly with medical treatments providing a large role in controlling endometriosis symptoms. Despite these advances we still lack an accurate noninvasive test to diagnose endometriosis. This has a large role in the delay to diagnosis, management and progression of the disease amongst a population that is choosing to conceive later.
Endometriosis is now thought to affect 1 in 10 women with patient annual healthcare costs estimated at &OV0556;9579. The diagnosis of this disease is still delayed by an average of 6-9 years allowing disease and symptom progression. Researchers have assessed a wide variety of noninvasive markers from urinary derivatives to MRI. There has been limited success in producing a highly sensitive and specific preoperative test for endometriosis. Novel markers such as miRNA provide the most encouraging diagnostic accuracy.
The development of a noninvasive accurate marker for endometriosis is a research target and priority of the European Society of Human Reproduction and Embryology. The current markers in use have moderate sensitivity and sensitivity. The inflammatory basis for the disease underpins many biomarkers but also many other concomitant diseases reducing accuracy and increasing false positive results.
Minerva Ginecol. 2016 Jun;68(3):250-8.
Causes of endometriosis and prevalent infertility in patients undergoing laparoscopy without achieving pregnancy.
DE Oliveira R1, Adami F, Mafra FA, Bianco B, Vilarino FL, Barbosa CP.
Endometriosis is a disease with an unknown pathogenesis that can lead to infertility. Endometrial polyps, fibroids, and polycystic ovarian syndrome (PCOS) have relatively high frequency and are causes of infertility. We hypothesized a possible relationship between the presence of polyps, fibroids, and PCOS in infertile women with endometriosis who underwent laparoscopy and did not get pregnant, compared to women in the control group.
This study was a cross-sectional study of 1243 infertile patients (621 with endometriosis and 622 controls). Endometriosis, Body Mass Index (BMI), infertility duration, age, and smoking habits were analyzed in relation to the presence of endometrial polyps, fibroids, and PCOS.
Polyps, 1.8 (95% CI 1.3-2.5); fibroids, 2.5 (95% CI 1.5-4.1); and PCOS, 1.0 (95% CI 0.6-1.6 were observed in the endometriosis group. A total of 285 patients (45.9%) were classified presenting endometriosisgrades I and II, and 336 patients (54.1%) with grades III and IV. Our findings showed a significant association between the presence of fibroids in 129 women with endometriosis (20.8%), and in 69 (53.9%) with endometriosis grades III and IV (P=0:04). Among the 31 PCOS patients, 24 (77.4%) showed grades I and II (P<0.001).
Endometriosis and infertility are associated with the presence of polyps and fibroids. Furthermore, associations between the presence of fibroids with endometriosis grades III and IV, and presence of PCOS with grades I and II were observed.
Semin Reprod Med. 2015 Jul;33(4):246-56.
Pathogenesis of Endometriosis: Roles of Retinoids and Inflammatory Pathways.
Taylor RN1, Kane MA2, Sidell N3.
Endometriosis is a nonmalignant, but potentially metastatic, gynecological condition manifested by the extrauterine growth of inflammatory endometrial implants. Ten percent of reproductive-age women are affected and commonly suffer pelvic pain and/or infertility. The theories of endometriosis histogenesis remain controversial, but retrograde menstruation and metaplasia each infer mechanisms that explain the immune cell responses observed around the ectopic lesions. Recent findings from our laboratories and others suggest that retinoic acid metabolism and action are fundamentally flawed in endometriotic tissues and even generically in women with endometriosis. The focus of our ongoing research is to develop medical therapies as adjuvants or alternatives to the surgical excision of these lesions. On the basis of concepts put forward in this review, we predict that the pharmacological actions and anticipated low side-effect profiles of retinoid supplementation might provide a new treatment option for the long-term management of this chronic and debilitating gynecological disease.
Reprod Sci. 2015 Sep;22(9):1060-72
Integrative Analysis Reveals Regulatory Programs in Endometriosis.
Yang H1, Kang K2, Cheng C3, Mamillapalli R4, Taylor HS5.
Endometriosis is a common gynecological disease found in approximately 10% of reproductive-age women. Gene expression analysis has been performed to explore alterations in gene expression associated with endometriosis; however, the underlying transcription factors (TFs) governing such expression changes have not been investigated in a systematic way. In this study, we propose a method to integrate gene expression with TF binding data and protein-protein interactions to construct an integrated regulatory network (IRN) for endometriosis. The IRN has shown that the most regulated gene in endometriosis is RUNX1, which is targeted by 14 of 26 TFs also involved in endometriosis. Using 2 published cohorts, GSE7305 (Hover, n = 20) and GSE7307 (Roth, n = 36) from the Gene Expression Omnibus database, we identified a network of TFs, which bind to target genes that are differentially expressed in endometriosis. Enrichment analysis based on the hypergeometric distribution allowed us to predict the TFs involved in endometriosis (n = 40). This included known TFs such as androgen receptor (AR) and critical factors in the pathology of endometriosis, estrogen receptor α, and estrogen receptor β. We also identified several new ones from which we selected FOXA2 and TFAP2C, and their regulation was confirmed by quantitative real-time polymerase chain reaction and immunohistochemistry (IHC). Further, our analysis revealed that the function of AR and p53 in endometriosis is regulated by posttranscriptional changes and not by differential gene expression. Our integrative analysis provides new insights into the regulatory programs involved in endometriosis.
Int J Mol Med. 2015 Sep;36(3):725-32.
Valproic acid-induced histone acetylation suppresses CYP19 gene expression and inhibits the growth and survival of endometrial stromal cells.
Chen Y1, Cai S1, Wang J1, Xu M1.
Endometriosis is a common type of estrogen‑dependent, gynecological and chronic inflammatory disease. Epigenetics refers to changes in gene expression that occur without altering the DNA sequence or DNA content. Histone modification dominates epigenetics, and histone acetylation is the most extensively studied type of histone modification. The CYP19 gene is the gene that encodes P450 aromatase, which regulates the synthesis of estrogen. Hence, we conducted this study to investigate whether histone acetylation has an effect on CYP19 expression and whether histone acetylation is related to endometrial stromal cells (ESCs). Reverse transcription-quantitative polymerase chain reaction (RT‑qPCR), western blot analysis and chromatin immunoprecipitation assays were performed. The results revealed that valproic acid (VPA) significantly promoted histone acetylation in the ESCs, which inhibited histone acetylation in the promoter region of the CYP19 gene, thus suppressing its expression. We also noted that VPA inhibited cell viability and proliferation, and induced the apoptosis, of ESCs. The findings of our study on histone acetylation, endometriosis and the CYP19 gene provide insight which may aid in the research of histone acetylation and suggest that the CYP19 gene may be a novel therapeutic target and method for the treatment of endometriosis.
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