Do exosomes play a role in the pathogenesis of endometriosis in a murine model? Exosomes from endometriosis (EMS) can alternatively activate macrophages and thus contribute to the development of lesions in mice. The pathogenesis of endometriosis, an inflammatory disease, possibly involves peritoneal macrophages. Exosomes are recognized as a new communicator among cells and a key modulator in several inflammatory diseases. We performed in vitr and in vivo experiments to demonstrate the role of exosomes in modulating macrophages. RAW264.7 cells (macrophages) were used to examine the effects of exosomes on macrophages in vitro. An experiment was also conducted in vivo, as follows. Fifty C57BL/6 female mice were randomly allocated to five control and five experimental groups (n = 5/group). The experimental group was injected i.p. with EMS-exosomes derived from eutopic stromal cells, starting on Day-7 then every day for 1 week. The control group received CON-exosomes from mice without endometriosis. Peritoneal macrophages were assessed over the next 6 days. On Day 0, all mice were injected i.p. with endometrium to establish the endometriosis model. On Day 14, all mice were sacrificed, ectopic lesions were counted and measured. Exosomes were isolated from endometrial stromal cells (ESCs) by ultracentrifugation and characterized through transmission electron microscopy, nanoparticle tracking analysis and western blot. After treatment with exosomes, the polarization and phagocytic ability of the macrophages were detected by flow cytometry analysis, immunofluorescent staining and RT-PCR. C57BL/6 mice were utilized to establish an endometriosis model by i.p. injection of endometrial segments. After treatment with EMS-exosomes, the macrophages were polarized into an M2-like phenotype and their phagocytic ability decreased (P < 0.05 versus treatment with CON-exosomes). The total weight and volume of the lesions in mice treated with EMS-exosomes significantly increased compared with those in mice treated with CON-exosomes (P < 0.05). The infiltration of M2-like macrophages was enhanced in the EMS-exosome group (P < 0.001 versus treatment with CON-exosomes). N/A Detection of endometriosis following exosome treatment was only performed in a murine endometriosis model. Clinical data and additional mechanism studies must be conducted to understand the role of exosomes in the pathogenesis of endometriosis. This study emphasizes the importance of EMS-exosomes in the pathogenesis of endometriosis. Further investigations on the exosome signaling pathways may contribute to the development of effective treatments for endometriosis. This research was supported by grants (Nos. 81571417 and 81771552) from the National Science Foundation of China. The authors report no conflict of interest.

Endometriosis is a common multifactorial gynecological disorder defined as the proliferation of endometrial tissue outside of the uterine cavity. Neuroangiogenesis (co-recruitment of nerves and blood vessels) is believed to play an integral part in the establishment and growth of endometriotic lesions. We hypothesized that exosomes derived from abnormal endometrium may serve as the second identifier of endometriosis and play an important role in the development of endometriosis by regulating neuroangiogenesis. Primary human endometrial stromal cells (ESCs) were isolated from eutopic endometrium (EmESC, n = 22) with endometriosis and normal endometrium (CoESC, n = 6). Exosomes were isolated from ESCs using “standard” ultracentrifugation method, and the characterization of exosomes were identified through transmission electron microscopy, nanoparticle tracking analysis, and western blot. The role of exosomes in regulating neuroangiogenesis was determined through in vitro tube formation assay, neurite outgrowth assay, and dorsal root ganglion (DRG) neuron apoptosis analysis. The data showed that EmESCs could secrete exosomes with a diameter of approximately 100 nm and a biconcave morphological feature; they were internalized by human umbilical vein endothelial cells (HUVECs) and DRG neurons and enhanced neuroangiogenic effects. We further validated the role of exosomes through blocking experiments. We found that when the exosome secretion was blocked, the pro-neuroangiogenesis effects were decreased. In conclusion, these data suggested that exosomes may play a key role in endometriosis by promoting neuroangiogenesis.

The main symptoms of adenomyosis may adversely affect physical and mental health and quality of life (QOL). However, studies are few on this topic. This study evaluated the effect of adenomyosis on anxiety, depression, and QOL. Participants with adenomyosis (n = 90) or leiomyoma (n = 59) completed questionnaires, including the visual analog scale (VAS) for pain, Hospital Anxiety and Depression Scale (HADS), and Short Form (SF)-36. HADS anxiety and depression positive rates, physical (PCS) and mental (MCS) component summary scores, and eight subscale scores of SF-36 were compared between the two groups. Among patients with adenomyosis, the incidence of anxiety symptoms was 28.9% (control group, 10.2%; OR = 3.589, 95% CI: 1.375–9.367), with 10% of patients showing moderate-to-severe symptoms. The incidence of depressive symptoms was 14.4% (control group, 3.4%; OR = 4.812, 95% CI: 1.044–22.168). The case group had significantly lower PCS and MCS scores than the control group. In patients with adenomyosis, being employed (OR = 6.393, 95% CI: 1.153–35.440) and perianal pain (OR = 25.419, 95% CI: 2.504–258.024) were risk factors for anxiety, and perianal pain (OR = 15.208, 95% CI: 3.050–75.836) was a risk factor for depression. Compared with leiomyoma, adenomyosis is associated with a higher risk of anxiety and depression, with a poorer QOL.