Lesion development is modulated by the natural estrous cycle and mouse strain in a minimally invasive model of endometriosis†

Abstract

Many rodent models of endometriosis are invasive, involving surgery to implant donor endometrial tissue into recipient animals. Moreover, few studies have compared and contrasted lesions between rodent strains and estrous stages without exogenous hormone manipulation. This is despite extensive data demonstrating that genetic and hormonal factors can influence endometriosis progression. Here, we have refined a minimally invasive model of endometriosis using naturally cycling mice (donor and recipient matched for cycle phase) to investigate lesion development in two different strains (C57BL/6 and BALB/c), induced in estrous stages of high and low estrogen (proestrus or estrus, respectively), and with varying amounts of donor endometrial tissue (7.5-40 mg), injected intraperitoneally. The overall probability of developing endometriosis-like lesions was higher in proestrus than estrus, and increased with greater masses of donor tissue. Similarly, the total number of lesions (0-3) increased from 7.5 to 40 mg, and was significantly greater in proestrus C57BL/6 mice but not BALB/cs. The dominant lesion type also differed between mouse strains; C57BL/6 mice were more likely to develop dense-type lesions, whereas BALB/c mice developed a greater proportion of cystic type. These data further support a role for estrogen in the development of endometriosis, and that genetic variance can influence the degree and characteristics of lesions. Our minimally invasive model would be beneficial for studies with outcome measurements particularly sensitive to incisional injury, such as pain, or alterations to sex hormones, including fertility.

Interleukin-1/-33 Signaling Pathways as Therapeutic Targets for Endometriosis

“…To clarify the role of IL-1 in lesion formation, we used C57BL/6-background IL-1R1-deficient mice for the endometriosis model. As previously reported, C57BL/6 mice exhibited smaller lesion formation than BALB/c mice (38). In Il1r1 −/− mice, only very small lesions were observed compared with WT mice (Figure 3C).…”

Mimicking Sampson’s Retrograde Menstrual Theory in Rats: A New Rat Model for Ongoing Endometriosis-Associated Pain

“…In accordance with Dodds et al, lesions were most often observed on the stomach and pancreas, although lesions could also be retrieved from other parts of the abdominal cavity (i.e., gonadal adipose tissue and intestines) [28]. The presence of adhered endometriosis lesions on the peritoneum or subcutaneously is most likely due to residual tissue fragments that were on the tip of the catheter when withdrawing the instrument from the abdominal cavity [28]. The proliferation of the endometriosis lesions was left under the control of the natural estrus cycle of the recipient animals.…”

“…This parameter was approximately 2 mg/g body weight in the mouse model [9], compared to 1.5 mg/g body weight in the rat endometriosis model. In accordance with Dodds et al, lesions were most often observed on the stomach and pancreas, although lesions could also be retrieved from other parts of the abdominal cavity (i.e., gonadal adipose tissue and intestines) [28]. The presence of adhered endometriosis lesions on the peritoneum or subcutaneously is most likely due to residual tissue fragments that were on the tip of the catheter when withdrawing the instrument from the abdominal cavity [28].…”

“…(B) The size of adhered ENDO lesions. Outline of rodent anatomy is adapted from Jackson Laboratories [38] and Dodds et al [28]. Figure S3.…”

Spinal Glial Adaptations Occur in a Minimally Invasive Mouse Model of Endometriosis: Potential Implications for Lesion Etiology and Persistent Pelvic Pain

“…To induce endometriosis-like lesions in mice, we employed a method previously developed by our laboratory. 31 This particular model was favored as it avoids surgery and exogenous hormone administration, which in themselves can alter glial reactivity [32][33][34] and therefore could confound results. Donor animals (n ¼ 5) were sacrificed by cervical dislocation while under deep inhaled isoflurane anesthesia.…”