Abstract
Endometriosis is a prevalent gynecologic disease, defined by dysfunctional endometrium-like lesions outside of the uterine cavity. These lesions are presumably established via retrograde menstruation, i.e., endometrial tissue that flows backwards during menses into the abdomen and deposits on the organs. As ongoing pain is one of the main pain symptoms of patients, an animal model that illuminates this problem is highly anticipated. In the present study, we developed and validated a rat model for ongoing endometriosis-associated pain. First, menstrual endometrial tissue was successfully generated in donor rats, as validated by gross examination, histology and qPCR. Next, endometriosis was induced in recipient animals by intraperitoneal injection of menstrual tissue. This resulted in neuro-angiogenesis as well as established endometriosis lesions, which were similar to their human counterparts, since epithelial and stromal cells were observed. Furthermore, significant differences were noted between control and endometriosis animals concerning bodyweight and posture changes, indicating the presence of ongoing pain in animals with endometriosis. In summary, a rat model for endometriosis was established that reliably mimics the human pathophysiology of endometriosis and in which signs of ongoing pain were detected, thus providing a new research tool for therapy development.
Highlights
10% of reproductive age women, i.e., 176 million women worldwide, suffers from endometriosis [1]
This resulted in neuro-angiogenesis as well as established endometriosis lesions, which were similar to their human counterparts, since epithelial and stromal cells were observed
The progesterone withdrawal at day 19 of the protocol resulted in the arrangement of menstrual endometrial tissue in rats, i.e., the menstruating rat model (MRM) (Figure 1A)
Summary
10% of reproductive age women, i.e., 176 million women worldwide, suffers from endometriosis [1]. In the beginning of the 20th century, Sampson postulated several theories of endometriosis development, such as vascular dissemination, celomic metaplasia and retrograde menstruation [2,3] The latter is the most likely to explain the location of the majority of cases of intra-abdominal endometriosis [2,3]. Retrograde menstruation stipulates that lesions arise from the blood and cells that are shed during menstruation, and are deposited in the abdomen via the fallopian tubes due to a backward menstrual flow [2] This process is regarded as non-pathological, as it occurs in 90% of menstruating women, and most women are able to clear this tissue over time [4]. In women with endometriosis, these menstrual endometrial cells are able to survive and flourish in the abdominal cavity, presumably by acquiring additional capacities, such as migration, adhesion, proliferation, immune evasion and triggering neuro-angiogenesis, culminating in endometriosis lesions [5]
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