Relevant human tissue resources and laboratory models for use in endometriosis research

Abstract

Endometriosis is characterized by the growth of endometrium-like tissue outside the uterus, most commonly on the pelvic peritoneum and ovaries. Although it may be asymptomatic in some women, in others it can cause debilitating pain, infertility or other symptoms including fatigue. Current research is directed both at understanding the complex etiology and pathophysiology of the disorder and at the development of new nonsurgical approaches to therapy that lack the unwanted side effects of current medical management. Tools for endometriosis research fall into two broad categories; patient-derived tissues, and fluids (and cells isolated from these sources) or models based on the use of cells or animals. In this review, we discuss the literature that has reported data from the use of these tools in endometriosis research and we highlight the strengths and weaknesses of each. Although many different models are reported in the literature, hypothesis-driven research will only be facilitated with careful experimental design and selection of the most appropriate human tissue from patients with and without endometriosis and combinations of physiologically relevant in vitro and in vivo laboratory models.

Keywords: Endometriosis; ex vivo; in vitro; in vivo; laboratory models.

Figure 1

The presence of endometriosis lesions impacts the reproductive system and the nervous system. Endometriosis lesions present within the pelvic cavity cause the defining symptoms of the condition, which are infertility and chronic debilitating pelvic pain. Lesions generate an inflammatory environment, which may have a negative impact on developing oocytes and implanting blastocysts. This inflammation is also thought to activate nerve fibers that innervate lesions. In addition to disease‐specific cellular and molecular changes, extensive lesions and adhesions can cause distortion of the pelvic organs and nerve compression that may also contribute to fertility problems and pain. Animal models of endometriosis are required to dissect out specific disease mechanisms that impact on the reproductive and nervous system. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 2

Research question specific models for the study of endometriosis. Many theories on the pathophysiology and etiology of endometriosis exist. Hypothesis‐driven research will be facilitated with careful experimental design and selection of appropriate human tissue from patients with and without endometriosis and appropriate combinations of in vitro and in vivo laboratory models. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 3

Peritoneal and endometriosis lesions collected at time of surgery. Taking biopsies of peritoneum from sites adjacent and distal to lesions in patients with endometriosis, and from sites prone to endometriosis in patients without the condition provides useful biological information when analyzed as additional controls within an experiment. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 4

Endometriosis lesions are multicellular tissue deposits. Typical endometriosis lesions contain endometrioid glandular structures (made up of epithelial cells) and stromal cells, similar to the eutopic endometrium. Lesions become vascularized, innervated and infiltrated by immune cells such as macrophages, mast cells and natural killer cells. Isolation of specific cell types from lesions is difficult due to the limited amount of tissue available from biopsies. In most cases the exploration of cellular interactions must be recreated using cell models and disease‐specific effects on physiology must be modeled in vivo. [Color figure can be viewed at wileyonlinelibrary.com]