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      Cellular and molecular basis for endometriosis-associated infertility

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          Abstract

          Endometriosis is a gynecological disease characterized by the presence of endometrial glandular epithelial and stromal cells growing in the extra-uterine environment. The disease afflicts 10%–15% of menstruating women causing debilitating pain and infertility. Endometriosis appears to affect every part of a woman’s reproductive system including ovarian function, oocyte quality, embryo development and implantation, uterine function and the endocrine system choreographing the reproductive process and results in infertility or spontaneous pregnancy loss. Current treatments are laden with menopausal-like side effects and many cause cessation or chemical alteration of the reproductive cycle, neither of which is conducive to achieving a pregnancy. However, despite the prevalence, physical and psychological tolls and health care costs, a cure for endometriosis has not yet been found. We hypothesize that endometriosis causes infertility via multifaceted mechanisms that are intricately interwoven thereby contributing to our lack of understanding of this disease process. Identifying and understanding the cellular and molecular mechanisms responsible for endometriosis-associated infertility might help unravel the confounding multiplicities of infertility and provide insights into novel therapeutic approaches and potentially curative treatments for endometriosis.

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          Endometriosis and infertility.

          Endometriosis is a debilitating condition characterized by high recurrence rates. The etiology and pathogenesis remain unclear. Typically, endometriosis causes pain and infertility, although 20-25% of patients are asymptomatic. The principal aims of therapy include relief of symptoms, resolution of existing endometriotic implants, and prevention of new foci of ectopic endometrial tissue. Current therapeutic approaches are far from being curative; they focus on managing the clinical symptoms of the disease rather than fighting the disease. Specific combinations of medical, surgical, and psychological treatments can ameliorate the quality of life of women with endometriosis. The benefits of these treatments have not been entirely demonstrated, particularly in terms of expectations that women hold for their own lives. Although theoretically advantageous, there is no evidence that a combination medical-surgical treatment significantly enhances fertility, and it may unnecessarily delay further fertility therapy. Randomized controlled trials are required to demonstrate the efficacy of different treatments.
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            The pains of endometriosis.

            Endometriosis is a disease defined by the presence of endometrial tissue outside of the uterus. Severe pelvic pain is often associated with endometriosis, and this pain can be diminished with therapies that suppress estrogen production. Many women with endometriosis also suffer from other chronic pain conditions. Recent studies suggest that mechanisms underlying these pains and sensitivity to estrogen involve the growth into the ectopic endometrial tissue of a nerve supply, which could have a varied and widespread influence on the activity of neurons throughout the central nervous system.
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              Nutrition, epigenetics, and developmental plasticity: implications for understanding human disease.

              There is considerable evidence for induction of differential risk of noncommunicable diseases in humans by variation in the quality of the early life environment. Studies in animal models show that induction and stability of induced changes in the phenotype of the offspring involve altered epigenetic regulation by DNA methylation and covalent modifications of histones. These findings indicate that such epigenetic changes are highly gene specific and function at the level of individual CpG dinucleotides. Interventions using supplementation with folic acid or methyl donors during pregnancy, or folic acid after weaning, alter the phenotype and epigenotype induced by maternal dietary constraint during gestation. This suggests a possible means for reducing risk of induced noncommunicable disease, although the design and conduct of such interventions may require caution. The purpose of this review is to discuss recent advances in understanding the mechanism that underlies the early life origins of disease and to place these studies in a broader life-course context.
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                Author and article information

                Contributors
                timmsk@health.missouri.edu
                Journal
                Cell Tissue Res
                Cell Tissue Res
                Cell and Tissue Research
                Springer-Verlag (Berlin/Heidelberg )
                0302-766X
                1432-0878
                3 February 2012
                3 February 2012
                September 2012
                : 349
                : 3
                : 849-862
                Affiliations
                Division of Reproductive and Perinatal Research, Department of Obstetrics, Gynecology and Women’s Health, The University of Missouri School of Medicine, 1 Hospital Drive, N 625 HSC, DC051.00, Columbia, MO 65212 USA
                Article
                1309
                10.1007/s00441-011-1309-0
                3429772
                22298022
                7353f7a4-0412-4032-b796-d8a621f0e55f
                © The Author(s) 2012
                History
                : 31 October 2011
                : 6 December 2011
                Categories
                Review
                Custom metadata
                © Springer-Verlag 2012

                Molecular medicine
                endometriosis,infertility,ovary,oocytes and embryos,endometrium
                Molecular medicine
                endometriosis, infertility, ovary, oocytes and embryos, endometrium

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