Pathogenesis of endometriosis: the role of genetics, inflammation and oxidative stress.
ABSTRACT Endometriosis is defined as the presence of endometrial tissue outside the uterine cavity.
The etiology of this multifactorial disease is still unresolved and an increasing number of studies suggest that genetic, hormonal, environmental, immunological and oxidative factors may all play an important role in the pathogenesis of this disorder.
In this literature review, inflammatory activity, oxidative stress as well as genetic abnormalities and mutations have been studied in an effort to identify factors predisposing to endometriosis.
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ABSTRACT: To explore a possible connection between endometriosis, Müllerian anomalies, and possession of the N314D allele of the gene for galactose-1-phosphate uridyl transferase (GALT), we studied 33 women with endometriosis attending a fertility clinic. Patients completed questionnaires and had DNA tested for the N314D mutation of GALT. A previously completed general population survey of 111 women which obtained the same information was available for comparison. Women with endometriosis were more likely to carry at least one N314D allele (30% compared with 14%) and more likely to report a medical history of scoliosis (21% compared with 2%) compared to general population controls: two features we have described in women with vaginal agenesis. Compared with endometriosis cases without the N314D allele, those cases with the allele tended to have more advanced disease and a family history of endometriosis. We speculate that endometriosis may arise due to defects of canalization of the cervix leading to cervical stenosis and retrograde menstruation. The relevance of the N314D mutation, via this model, may derive from an association between abnormalities of galactose metabolism and vaginal agenesis which represents a canalization defect of the vaginal plate of the Müllerian tubercle, the same structure which gives rise to the cervix.Molecular Human Reproduction 04/1996; 2(3):149-52. · 4.54 Impact Factor
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ABSTRACT: To investigate whether polymorphisms of CYP17 and CYP19 genes are associated with the risk of endometriosis, we analysed the frequency and distribution of a single nucleotide polymorphism at the 5' untranslated region of the CYP17 gene, and a tetranucleotide (TTTA) tandem repeat polymorphism and a 3 bp insertion (I)/deletion (D) polymorphism in intron 4 of the CYP19 gene. We studied 140 patients with endometriosis, 67 with adenomyosis and/or leiomyomas and 177 healthy control women. The distribution of the genotypes of CYP17 and alleles of the TTTA repeat polymorphism of CYP19 were not significantly different between the groups. In contrast, an increased frequency of the D/D genotype was observed in the endometriosis group as compared with the control group (D/D genotype versus I/I plus I/D genotypes; corrected P = 0.024). This was more evident in the endometriosis subgroups with chocolate cysts (corrected P = 0.043) and at severe clinical stages (corrected P = 0.035). The results suggest that the 3 bp I/D polymorphism of the CYP19 gene may be weakly associated with the susceptibility of endometriosis in a Japanese population.Human Reproduction 05/2002; 17(4):897-902. · 4.67 Impact Factor
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ABSTRACT: To determine whether vitamins C and E supplementation lowers oxidative stress marker levels and improves pregnancy rate in women with endometriosis. Thirty-four women with endometriosis received a bar containing vitamins C and E (343 mg and 84 mg, respectively) or placebo for 6 months. Plasma and peritoneal fluid levels of malondialdehyde (MDA) and lipid hydroperoxides (LOOHs) were measured for all women and compared between the 2 groups. Data were analyzed by the t test or 1-way analysis of variance for parametric data and the Mann-Whitney rank sum test or Kruskall-Wallis test for nonparametric data. The Fisher exact test was used to compare pregnancy rates. After 4 months, the study group had lower levels of MDA and LOOHs than the control group, and the difference became statistically significant in the fourth month for MDA levels and in the sixth month for LOOH levels. The postintervention pregnancy rates were 19% and 12% in the supplementation and placebo groups, respectively, but the difference was not significant. Vitamins C and E supplementation was associated with a decrease in the concentration of oxidative stress markers in women with endometriosis. The pregnancy rate, however, did not improve during or after the intervention.International Journal of Gynecology & Obstetrics 04/2008; 100(3):252-6. · 1.84 Impact Factor