Data from: Macrophage migration inhibitory factor is involved in ectopic endometrial tissue growth and peritoneal-endometrial tissue interaction in vivo: a plausible link to endometriosis development

Pelvic inflammation is a hallmark of endometriosis pathogenesis and a major cause of the disease's symptoms. Abnormal immune and inflammatory changes may not only contribute to endometriosis-major symptoms, but also contribute to ectopic endometrial tissue growth and endometriosis development. A major pro-inflammatory factors found elevated in peritoneal fluid of women with endometriosis and to be overexpressed in peritoneal fluid macrophages and active, highly vascularized and early stage endometriotic lesions, macrophage migration inhibitory factor (MIF) appeared to induce angiogenic and inflammatory and estrogen producing phenotypes in endometriotic cells in vitro and to be a possible therapeutic target in vivo. Using a mouse model where MIF-knock out (KO) mice received intra-peritoneal injection of endometrial tissue from MIF-KO or syngeneic wild type (WT) mice and vice versa, our current study revealed that MIF genetic depletion resulted in a marked reduction ectopic endometrial tissue growth, a disrupted tissue structure and a significant down regulation of the expression of major inflammatory (cyclooxygenease-2), cell adhesion (αv and β3 integrins), survival (B-cell lymphoma-2) and angiogenic (vascular endothelial cell growth) factorsrelevant to endometriosis pathogenesis, whereas MIF add-back to MIF-KO mice significantly restored endometriosis-like lesions number and size. Interestingly, cross-experiments revealed that MIF presence in both endometrial and peritoneal host tissues is required for ectopic endometrial tissue growth and pointed to its involvement in endometrial-peritoneal interactions. This study provides compelling evidence for the role of MIF in endometriosis development and its possible interest for a targeted treatment of endometriosis

Primer sequences for RT-qPCR.

<p>Primer sequences for RT-qPCR.</p

Effect of rhMIF add-back in KO mice or specific inhibition of MIF in WT mice on the development of endometriosis-like lesions.

<p>Wild type (WT) mice; MIF knock out (KO) mice; rhMIF, KOmice treated with rhMIF; ISO-1, WTmice treated with ISO-1; Vehicle, mice treated with PBS instead of rhMIF in KOmice or ISO-1 in WTmice. Data are from 5 mice per group and expressed as mean ± SEM.</p>a<p>p< 0.05 and ^bp< 0.01 compared with the corresponding vehicle-treated group.</p><p>Effect of rhMIF add-back in KO mice or specific inhibition of MIF in WT mice on the development of endometriosis-like lesions.</p

Development of endometriosis-like lesions in KO mice <i>versus</i> WT mice.

<p>WT, wild type mice; KO, MIF knock out mice.</p><p>Data are from 6 mice per group and expressed as mean ± SEM.</p>b<p>p< 0.01 and ^cp< 0.001, compared with control (WT mice receiving WT endometrial tissue).</p><p>Development of endometriosis-like lesions in KO mice <i>versus</i> WT mice.</p

Immunostaining of PCNA in murine endometrial implants.

<p>PCNA immunostainingwas carried out on endometrial implants from KO/KO mice (A), WT/WT mice (B) and mice treated with ISO-1 (C) or rhMIF (D). Insets show general histological views of endometrial implants. Black arrows show CD74 positive cells. Scale bar,10 µm.</p

Development of endometriosis-like lesions in KO/KO mice and control WT/WT mice.

<p>Endometriosis-like lesions in KO/KO mice and control WT/WT mice were numbered and their sizes measured under fluorescence stereomicroscopy at sacrifice (A, B). Parallel experiments were performed where rhMIF (0.008 mg/kg) was added back to KO/KO mice (C, D), while ISO-1 (4 mg/kg) was used to treat WT/WT mice (E, F). Data are from 5 or 6 mice per group and expressed as mean ± SEM;*, p< 0.05, **, p< 0.01 and ***, p< 0.001 compared with the corresponding control group with the unpaired t-test.</p

Effect of endometrial tissue inoculation and treatment on the body weight and survival rate of animals.

<p>Mice were treated with ISO-1 (4 mg/kg) (A, B), rhMIF (0.008 mg/kg) (C, D). Control mice were treated with the vehicle (PBS). Data are means ± SEM from 5 mice treated with ISO-1, 5 mice treated with rhMIF and 10 mice treated with the vehicle.</p