Dose-Dependent Decreased Fertility in Response to the Burden of Endometriosis in a Murine Model

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.