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. 2020 Jan 14;9:e50356. doi: 10.7554/eLife.50356

Figure 1. Behavioral and histological alterations in female mice with ectopic endometrial implants.

Endometriosis mice showed (a) persistent mechanical abdominal hypersensitivity that (b) was localized in the caudal abdominal area but not detectable in distant areas (hind paw). Mechanical sensitivity is represented by the area under the curve of frequency of response to von Frey filaments. Higher values mean higher mechanical pain. Mice receiving endometrial implants also showed (c) increased nocifensive behavior, (d) anxiety-like behavior in the elevated plus maze test and (e) cognitive impairment in the novel object recognition task. (f) From left to right: cysts were recovered from endometriosis mice, were filled with fluid (scale bar = 1 mm), contained endometrial epithelium and stroma (scale bar = 100 μm) and were innervated by beta-III tubulin-labeled fibers (scale bar = 100 μm, blue is DAPI and white is β-III tubulin). Error bars are mean ± SEM. One-way repeated measures ANOVA + Bonferroni (a and b) and Student t-test (c, d and e). *p<0.05, **p<0.01, ***p<0.001 vs sham. ##p<0.01, ###p<0.001 vs baseline. Endo, endometriosis, AUC, area under the curve.

Figure 1—source data 1. Effects of ectopic endometrium.

Figure 1.

Figure 1—figure supplement 1. Nociceptive responses to abdominal mechanical stimulation with von Frey filaments.

Figure 1—figure supplement 1.

(a) Significantly higher frequency of responses and AUC was observed in endometriosis mice when compared to sham mice on days 14, 21 and 28 after the surgery. For each day, left panel is frequency of response to each von Frey filament and right panel is the corresponding mechanical sensitivity represented by the area under the curve of frequency of response to von Frey filaments. Higher values mean higher mechanical pain. (b) Site of application of the von Frey filaments (Test area). Error bars are mean ± SEM. For each day, one-way repeated measures ANOVA (left panels) and Student t-test (right panels). *p<0.05, **p<0.01 vs sham. Endo, endometriosis; AUC, area under the curve.
Figure 1—figure supplement 2. Nociceptive responses to abdominal and paw mechanical stimulation with von Frey filaments.

Figure 1—figure supplement 2.

(a) Frequency of responses to von Frey filaments applied against the caudal abdominal area and corresponding AUCs on day 14 after surgery were significantly higher in endometriosis mice when compared to sham mice. (b) Frequency of responses to von Frey filaments applied against the hind paw and corresponding AUCs were similar before and after surgery in endometriosis and sham mice. For each day, left panel is frequency of response to each von Frey filament and right panel is the corresponding mechanical sensitivity represented by the area under the curve of frequency of response to von Frey filaments. Higher values mean higher mechanical pain. Error bars are mean ± SEM. One-way repeated measures ANOVA (left panels) and Student t-test (right panels). ***p<0.001 vs sham. Endo, endometriosis; AUC, area under the curve.
Figure 1—figure supplement 3. Density of beta-III tubulin-labeled fibers in uteri of endometriosis and sham mice.

Figure 1—figure supplement 3.

(a) The percentage of immunoreactive area of the mesometrial aspect of the uterus was higher in endometriosis mice. (b) The percentage of immunoreactive area of myometrium did not differ between groups. Blue is DAPI and white is β-III tubulin. Scale bar = 100 μm. Error bars are mean ± SEM. Student t-test. **p<0.01 vs sham. Endo, endometriosis.