Using Rats as a Research Model for the Study of Endometriosis

Abstract

Although there are disadvantages of extrapolating data across species, the rat model may be used to study events involved in the pathogenesis and pathophysiologies of endometriosis or novel therapeutic approaches for this disorder that are not accessible in humans. Rat endometriotic tissues are similar to human lesions in vivo, and rat endometriotic tissues and cells perform in a similar manner as human endometriotic tissues and cells in organ explant culture and isolated cell culture. The rat model permits studies of mechanisms and regulators in a controlled manner free from confounding influences such as individual patient variation and environmental influences. The primary method used for induction of endometriosis in rats has been autotransplantation of uterine squares (implants) into the peritoneal cavity. Beyond mere growth of endometrium in ectopic locations, rats with endometriosis display similar symptoms, including a reduction in fertility and fecundity, and the endometriotic implants react similarly to therapeutics as those of humans with the disease. Similar alterations in gene expression and protein production have been observed in endometriotic tissues from rats and humans that may, in part, be causative agents involved in the pathogenesis or pathophysiologies of endometriosis.

Innervation of ectopic endometrium in a rat model of endometriosis

“…There are obviously, however, clear differences between this model and ENDO in women (10). For example, we do not yet know whether the rats exhibit chronic pelvic pain symptoms other than vaginal hyperalgesia.…”

“…Regardless of the mechanisms by which the cysts become innervated, the demonstration of a robust sensory innervation by C fibers raises the distinct possibility that this innervation contributes to both the vaginal hyperalgesia and the reduced fertility that occur in this rat model (9,10), probably via central effects, as follows. The cysts are known to contain proinflammatory cytokines, prostaglandins, and other neuroactive agents (8,10) that could readily activate the CGRP-and SP-positive C-fiber nociceptive afferents (32,33) found here to be located in the cyst's epithelium.…”

“…The cysts are known to contain proinflammatory cytokines, prostaglandins, and other neuroactive agents (8,10) that could readily activate the CGRP-and SP-positive C-fiber nociceptive afferents (32,33) found here to be located in the cyst's epithelium. Although the route by which the information conveyed by these activated fibers enters the CNS is not yet known, given the location of the cysts in the upper abdomen, it is most likely that this route will be found to include the splanchnic nerve, with fibers traveling in the superior mesenteric, inferior mesenteric, and celiac ganglia to the lower thoracic͞upper lumbar segments (9,11).…”

“…Specifically, the cysts in rats and the growths in women respond similarly to steroids, and the cysts synthesize or induce synthesis by cultured peritoneal cells of many of the same abnormal substances found in the ectopic endometrial growths and peritoneal fluid of women with ENDO (10). This rat model, therefore, seems suitable for investigating new ideas concerning mechanisms underlying signs and symptoms of ENDO (9,10). Accordingly, here we tested the hypothesis that the cysts in this rat model develop their own nerve supply and then determined whether that supply included both sensory and sympathetic efferent fibers.…”

Molecular profiling of experimental endometriosis identified gene expression patterns in common with human disease

“…Despite the clear advantages of using animal models in biomedical research, whether results obtained using experimental models of disease could be extrapolated to the human scenario remains controversial (4)(5)(6)(7). Therefore, animal models need to be carefully evaluated to ensure that they accurately represent the disease they are meant to mimic.…”