Female reproductive disease, endometriosis: From inflammation to infertility

Abstract

Despite the fact that endometriosis is a common gynecological disease that occurs in 10% of women of reproductive age, the pathogenesis and treatment strategy are not clear to date. Endometriosis patients are commonly characterized by adhesions in the pelvis or ovaries, which leads to prolonged inflammation in the abdominal cavity. To handle the chronic inflammation, changes of immune cells, including T cells, NK cells, and macrophage, are accompanied. Therefore, diverse cytokines and adhesions of the abdominal cavity lead to poor quality of ovarian follicles, inappropriate response to the hormone, and infertility. This review will guide researchers to summarize the molecular changes and identify new treatment strategies for endometriosis-mediated inflammation and pregnancy failure.

Keywords: Endometriosis pathology; Immune responses; Implantation failure; Inflammatory environment.

Fig. 1

Illustration provides information on the mechanism and complications of endometriosis. The 5 hypotheses are considered to be the main causes of endometriosis: (1) reflux of endometrial tissue by retrograde menstruation and transplantation to abnormal locations, (2) growth of endometrial tissue by hormonal imbalance, (3) induction of excessive inflammatory environment by abnormal functions of immune cells, (4) genetic factors, and (5) environmental factors. These pathogeneses might form lesions in various intraperitoneal organs such as ovaries, uterus, small intestine, and colon. In addition, endometriosis might be triggered by various pregnancy-related complications, such as maternal metabolic disorders, abnormal placenta, and small fetus.

Fig. 2

An inflammatory environment of endometriosis is caused by dysregulated immune cells. (1) Alteration of T-cell subpopulation in peritoneal and endometriotic lesions is identified. Increased T_reg cells contribute to the survival of endometriosis cells by reducing immune surveillance. In addition, Th1/Th2 balance switches to Th2 predominant direction. (2) The cytotoxicity of natural killer (NK) cells was inhibited by endometriosis stromal cells. The defected function of NK cells might induce survival of endometriosis cells. (3) Macrophages, the predominant immune cells in the peritoneal cavity, regulate various inflammatory cytokines and induce an inflammatory response. This activated inflammatory response accelerates the progression of endometriosis lesions.

Fig. 3

The effects of endometriosis on infertility and the treatment options of infertility with endometriosis are schematically illustrated. Endometriosis causes anatomical distortion of the female reproductive system and problems, such as the inflammation and reduction of ovarian reserves. In particular, the inflammatory environment of female reproductive system reduces sperm mobility and uterine receptivity through induction of progesterone resistance in the endometrium. Endometriosis may contribute to unexplained infertility. Infertility patients with endometriosis should consider the following treatment methods for endometriosis before ART to improve ART outcomes: (1) surgical removal of endometriosis, (2) pharmacological treatment (antioxidants or anti-inflammatory drugs), and (3) hormone therapy.