Endometriosis Factor Research Articles

L1 cell adhesion molecule (L1CAM) as a pathogenetic factor in endometriosis

Endometriosis is a benign and progressive disease with a high prevalence. Women with endometriosis, especially with atypical endometriosis, have a higher probability for developing ovarian cancer compared with women without endometriosis. The L1 cell adhesion molecule (L1CAM) is over expressed in ovarian and endometrial carcinomas and is associated with a bad prognosis. Here, we have analysed L1CAM expression in endometriosis. In our study with the samples from 79 patients with, and 37 patients without, endometriosis, we found that endometriosis cell lines and short-term cultures of endometrium from women with endometriosis expressed L1CAM at the mRNA and protein level. Quantitative RT-PCR analysis showed that L1CAM was expressed at significantly higher level in the epithelial compartment from patients with endometriosis compared with healthy controls (P = 0.0126). By immunohistochemical staining, 15 of 31 ovarian endometriotic lesions (48%) were shown to have L1CAM-positive staining. Of these 15 L1CAM-positive samples, 13 were atypical endometriotic lesions. Soluble L1 present in the conditioned medium of epithelial endometrium cultures from women with endometriosis was able to stimulate neurite outgrowth as measured in a chicken ganglion assay. We propose that L1CAM could promote endometriosis development by increasing enervation and aggravation. L1CAM expression is higher in atypical endometriosis compared with normal endometriosis.

Increased rate of endometriosis and spontaneous abortion in an in vitro fertilization program: No correlation with epidemiological factors

Background. There are conflicting data concerning endometriosis and spontaneous abortion (SAB). The aim of the present study was to evaluate if there was any association between endometriosis and SAB. Moreover, we investigated risk factors in women with endometriosis and SAB.Methods. The medical files of 457 married women with endometriosis and 200 infertile women without endometriosis were studied retrospectively. All cases were diagnosed by laparoscopy. Data concerning demographic variables and menstrual characteristics were recorded from 226 women with endometriosis, which were divided into two groups. Group 1 included 126 cases with endometriosis and SAB, and Group 2 comprised 100 parous women with endometriosis and without SAB. Statistical comparisons between groups were made using the χ2 test and odds ratios (OR) and 95% confidence intervals (CI).Results. The proportion of SAB was significantly higher in women with endometriosis than in infertile women without endometriosis (126/457 (27.6%) vs. 36/200 (18.0% ); OR = 1.7, 95% CI 1.1 = 2.6; p = 0.01). The frequency of nulligravid women was significantly higher in women with endometriosis than in the control group (OR = 1.9, 95% CI 1.4 – 2.81; p = 0.001). Mean age, age at onset of endometriosis, race, height, weight, body mass index, medical history of allergies, and family histories of endometriosis and cancer were similar in women with endometriosis and SAB and in parous women with endometriosis but without SAB. Moreover, the two groups were similar in age at menarche, length of cycle, duration and amount of flow, and the severity of disease. The incidence of infertility was significantly higher in women with SAB (p < 0.001).Conclusion. These data suggest but do not prove that the risk of SAB is increased in women with endometriosis. The epidemiological risk factors of endometriosis are not associated with an increase in the abortion rate.

Expression of angiogenic factors in endometriosis: relationship to fibrinolytic and metalloproteinase systems

Endometriosis is a highly prevalent, benign disease in which the angiogenic, fibrinolytic and metalloproteinase (MMP) systems may be implicated. The objective of this study is to analyse mRNA expression and protein levels of several angiogenic factors and to correlate them with several components of the fibrinolytic and MMP systems in samples from 71 women with endometriosis and 50 controls. Eutopic endometrium showed higher mRNA expression of vascular endothelial growth factor (VEGF) in patients than in controls. However, ovarian endometrioma had lower VEGF mRNA levels than did the eutopic endometrium of patients. Similar results were obtained for VEGF protein levels. On the other hand, a significant increase in thrombospondin-1 (TSP-1) levels was observed in ovarian endometrioma than in eutopic endometrium. The peritoneal fluid from women with endometriosis showed a significant increase in VEGF, urokinase-type plasminogen activator (uPA) and MMP-3 levels than that of controls. A significant correlation was observed between the levels of VEGF and uPA in endometrium and in peritoneal fluid. Endometrium and peritoneal fluid from women with endometriosis have increased levels of VEGF, uPA and MMP-3 levels. Therefore, the development of endometriotic implants at ectopic sites may be facilitated, promoting the progress of the endometriosis.

Environmental and host-associated risk factors in endometriosis and deep endometriotic nodules: A matched case–control study

Peritoneal endometriosis (PE) and deep endometriotic nodules (DEN) are gynecological diseases recently shown to be associated with elevated serum concentrations of organochlorines. The objective of the present study was to compare risk factors associated with both forms of the disease, with a particular attention to potential sources of organochlorine exposure. This matched case–control study with prospective recruitment included 88 triads (PE–DEN–control). All women were face-to-face interviewed with a standardized questionnaire, and serum dioxin and polychlorinated biphenyl measurements were available for 58 of them. Alcohol consumption (odds ratio (OR): 5.82 [confidence interval at 95% (95%CI) 1.20–28.3]) in DEN and low physical activity at work for DEN (OR: 4.58 [95%CI 1.80–11.62]) and PE (OR: 5.61 [95%CI 1.90–16.60]) were traced as significant risk factors. Organochlorine-related factors (use of tampons, occupational or environmental exposure) were not related to the disease. The current consumption of foodstuffs that were more likely to contribute to organochlorine body burden did not differ among the groups. Only some of these fatty foodstuffs (marine fish, pig meat) were traced by multiple regression analysis as significant determinants of organochlorine body burden, explaining only a small fraction (20%) of the interindividual variation of organochlorine body burden. We conclude that PE and DEN share similar patterns of risk or protective factors.

Treatment with piroxicam before embryo transfer increases the pregnancy rate after in vitro fertilization and embryo transfer

To examine the effect of beta-cyclodextrin piroxicam treatment for priming of the uterus on the pregnancy outcome of IVF-embryo transfer (ET) programs. Prospective, randomized, double-blinded placebo-controlled clinical study. Large urban medical center. One hundred eighty-eight consecutive cycles of fresh IVF-ET and 78 cycles of frozen-thawed ET. The patients underwent IVF because of tubal, male infertility, unexplained, or endometriosis factors. They were randomly divided into treatment and control groups. In the treatment group, 94 cycles in fresh ET and 39 cycles in frozen-thawed ET the patients received an oral dose of 10 mg of piroxicam. In the control group, the same number cycles corresponding to the treatment group were treated with placebo. Both groups started piroxicam or placebo treatment 1-2 hours before ET. Patients and staff were blinded to the treatment. Implantation rate (IR) and pregnancy rate (PR). Piroxicam increased significantly IR (18.7%) and PR (46.8%) compared to the control group (8.6% and 27.6%, respectively) in fresh cycles. With the exception of an unexplained factor, patients with the tubal, male infertility, or endometriosis factor had significantly higher PR in the treatment group compared to the control group. The beneficial effect of piroxicam was found in patients less than 40 years old, but was not found in patients more than 40 years. In frozen-thawed cycles, there were statistically significant differences between the treatment group and the control group in IR (9.4% vs. 2.3%) and PR (25.6% vs. 7.7%), respectively. Our study showed that piroxicam increases IR and PR after IVF-ET in both fresh and frozen-thawed ET cycles. The beneficial effect seems to be more remarkable in patients less than 40 years old with tubal, male infertility, or endometriosis factors. These results suggest that piroxicam treatment before ET is very effective in the priming of a uterus suitable for embryo implantation. This is the first study to investigate the possible consequence of piroxicam for improving the PR after IVF-ET.

N-acetyl transferase 2 polymorphism and advanced stages of endometriosis in South Indian women

Aylamine- N-acetyl transferase is a phase II detoxification enzyme encoded by the gene NAT2. Single nucleotide polymorphism (SNP) changes from the wild type NAT2 *4 allele result in allelic variants *5, *6 and *7. Homozygotes for the NAT2 *4 wild type are fast acetylators; heterozygotes with one wild-type allele and a variant NAT2 *5, *6 or *7 allele have reduced enzyme activity and individuals with two variant alleles are slow acetylators. Previous studies have implicated NAT2 as a susceptibility factor in endometriosis. This study investigated the NAT2 allele frequencies and genotype distributions in 252 unrelated women with endometriosis and 264 controls of South Indian origin. No differences were found between the frequencies of fast and slow acetylators in cases (34.9% and 65.1%) and controls (33.3% and 66.7%). Two NAT2 genotypes *7/*7 (1.2%) and *5/*6/*7 (1.6%) were detected in endometriosis cases only. Four new combinations, 6D (481 + 590 mutation), 7C (590 + 857), 7D (590 + 803 + 857) and 7E (481 + 590 + 803 + 857) were detected, which have not been reported earlier. Similar genotype and phenotype results were obtained in 33 affected sister-pairs. The case–control data from this study suggest there is no association between endometriosis and NAT2 in South Indian women; however, two new variant genotypes and seven SNP combinations were also identified in cases only, which suggests that the gene may still have some as yet undetermined role in the disease.

Angiogenic Factors in Endometriosis

Similar to tumor metastases, endometriotic implants require neovascularization to establish, grow, and invade. The peritoneal environment is ideally suited to provide a proangiogenic milieu. Nevertheless, endometriotic lesions are found only in a minority of reproductive-age women (approximately 10%) with retrograde menstruation. In this paper, we review the major cytokines, growth factors, steroid hormones, and eicosanoids responsible for angiogenesis in endometriosis. We postulate that interference with angiogenic principles expressed in the peritoneum may constitute novel therapeutic opportunities for the prevention, amelioration, or treatment of pelvic endometriosis.

Environmental contaminants and dietary factors in endometriosis.

Endometriosis is an estrogen-dependent disease characterized by the presence of endometrial glands and stroma outside the uterine cavity. The etiology of this disease remains elusive, but is clearly influenced by genetic, immune, and endocrine factors. Exposure to environmental contaminants has recently been added to the list of potential factors that contribute to the pathogenesis of endometriosis. The objective of this paper is to review the weight of the evidence from hospital-based case-control studies and animal experiments for an association between exposure to environmental contaminants and endometriosis.

Association between endometriosis and N-acetyl transferase 2 polymorphisms in a UK population.

The relationship between endometriosis and polymorphisms in the N-acetyl transferase 2 (NAT 2) gene was investigated in a UK population, as this gene has been previously implicated in the aetiology of the disease. Point mutations in the gene result in the variant alleles NAT 2 *5, *6 and *7 from the wild-type NAT 2 *4 allele. Homozygotes for the NAT 2 *4 wild type allele are fast NAT acetylators, while heterozygotes with one wild-type allele and a variant NAT 2 *5, *6 or *7 allele have reduced enzyme activity, and individuals with two variant alleles are slow acetylators. The NAT 2 *4/*6 genotype was significantly more common among affected women (35.2%) than population controls (8.1%; P = 0.0001) or unaffected women (4.2%; P = 0.02). Significantly more affected women (57.4%) were fast acetylators than were population controls (32.3%; P < 0.01) or unaffected women (33.3%; P < 0.05). These data suggest that altered NAT 2 enzyme activity may be a predisposition factor in endometriosis, or that NAT 2 alleles may be in linkage disequilibrium with a susceptibility allele in the same chromosomal region.

Erythropoietin concentrations are elevated in the peritoneal fluid of women with endometriosis.

Erythropoietin (Epo) is an important regulator of erythropoiesis and stimulates the proliferation of early erythroid precursors as well as the differentiation of late erythroid precursors of the erythroid lineage. However, recent studies have indicated that Epo also has angiogenic properties and plays an important role in the oestrogen-dependent cyclical angiogenesis within the mouse uterus. It was therefore postulated that Epo may be an important angiogenic factor in endometriosis. In order to address this hypothesis the concentration of Epo in peritoneal fluid (PF) was determined in patients with or without endometriosis. PF was collected from patients with endometriosis (n = 42) or without endometriosis (n = 18). Detectable concentrations of Epo were found in all PF samples analysed. The concentration of Epo in PF from patients with endometriosis was significantly higher than that in the control group (13.1 +/- 1.2 mIU/ml versus 7.2 +/- 0.7 mIU/ml, mean +/- SE respectively, P < 0.01). Furthermore, in patients with endometriosis the Epo concentrations in PF from patients with stage I disease (n = 17, 16.6 +/- 3.0 mIU/ml) were significantly higher than those with stage II (n = 8, 10.7 +/- 1.2 mIU/ml, P < 0.03), III (n = 13, 8.4 +/- 1.0 mIU/ml, P < 0.01), IV disease (n = 7, 7.5 +/- 1.0 mIU/ml, P < 0.01). These data suggest that Epo may play a role in the pathogenesis of endometriosis particularly in the initiation of the disease.

Will we be taught ethics by our clones? The mutations of the living, from endocrine disruptors to genetics

Considering the worldwide threat to health and reproduction related to endocrine disruptors (by-products of the chemical industry); considering the untrammelled development of the industrialization and engineering of the living, ethics and gynaecology/obstetrics itself is at a crossroads. Endocrine disruptors (derived from organochlorines and persistent organic pollutants such as PCBs, dioxins and furans, and pesticides such as aldrin, chlordane and DDT), are prime suspects in the deterioration of fertility and intellectual faculties and possibly a key factor in endometriosis, breast cancer and prostate cancer. The long-term and pernicious impacts of endocrine disruptors show our poor understanding of the complexities of lifeÕs mechanisms. Paradoxically, with our short-term perspectives and predilection for a technological fix, the problem posed by endocrine disruptors may accelerate the use of reproductive technologies such as ICSI and even cloning, as well as the dissemination of genetically modified organisms. The cure could be worse than the disease.Given the gravity of the challenge to humanity related to the chemical erosion of human health, the mutation of human conception introduced by reproductive technologies and by the drive to genetically modify nature and even human nature, we must urgently re-evaluate the direction in which our societies are headed and the reliance on profit-oriented technology to save us from ourselves. In these circumstances, the collective exercise of wisdom, prudence and responsibility towards the essence and integrity of humanity has become, more than ever, an ethical, and perhaps even a survival, imperative.

Interleukin-8: a growth promoting factor in endometriosis.

Interleukin-8: a growth promoting factor in endometriosis.

Additional Sterility Factors in Endometriosis

Additional Sterility Factors in Endometriosis