Dose-Dependent Decreased Fertility in Response to the Burden of Endometriosis in a Murine Model
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Reproductive Sciences 1-6 ª The Author(s) 2019 Article reuse guidelines: sagepub.com/journals-permissions DOI: 10.1177/1933719119859438 journals.sagepub.com/home/rsx
Ana C. J. S. Rosa-e-Silva, MD, PhD1, Julio C. Rosa-e-Silva, MD, PhD1, Ramanaiah Mamillapalli, PhD1 , and Hugh S. Taylor, MD1
Abstract Endometriosis is a gynecological disease caused by the growth of endometrial cells outside the uterus leading to inflammation, pelvic pain, and infertility. The relationship between the amount of ectopic uterine tissue growth and the severity of symptoms is still unclear. The presence or degree of pain and infertility does not correlate with the stage of disease as currently defined. Here, we report a clear dose–response relationship between the amount of ectopic tissue transplanted and the reproductive outcomes in a murine model of endometriosis. Endometriosis was induced in mice using various amounts of transplanted uterine tissue. Four groups of mice consisted of a sham surgery control or those transplanted with 1, 2, or 4 endometrial segments of 5 mm each. Pregnancy rates were significantly lower in those transplanted with 2 or 4 segments compared to sham or the 1 segment groups. We demonstrate that infertility does correlate with the extent of active disease. Current clinical staging systems do not account for disease activity and may inappropriately weight sequela of disease. Early recognition and treatment in women may help to minimize the effect of endometriosis on fertility. Here, we describe a mouse model of endometriosis and infertility that may be useful to elucidate the mechanisms of infertility in endometriosis. Keywords mice, endometriosis, uterine tissue, pregnancy, infertility, stage
Introduction Endometriosis is a gynecological disease characterized by the presence of endometrial glandular and stromal cells existing in extrauterine locations.1 In women, the clinical features vary considerably, from complete lack of any symptoms to severe pelvic pain and/or infertility. Paradoxically the clinical manifestations do not correlate with the extent of endometriosis seen at the time of surgery. The role of endometriosis in infertility is still controversial, as there are many mechanisms by which fertility may be impaired.2 One cause of infertility in these patients relates to tubal factor where an obstruction is evident; however, in most patients no anatomic alterations are found yet fertility is frequently compromised. Endometriosis has also been associated with impaired number and quality of oocytes,3,4 alterations in the pituitary function,4-6 impaired spontaneous ovulation,7 impaired fertilization,8-10 poor quality of preimplantation embryos,8,9 luteal phase endometrial defects,11,12 increased implantation failure,13 and increased pregnancy loss.9 The mechanisms that lead to infertility are still not fully characterized. Spontaneous endometriosis occurs only in humans and some primates that shed endometrium during a menstrual cycle,14 a characteristic that seems to be mandatory in the establishment
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