Background: Endometriosis is a common nonmalignant gynecological disorder that affects 10–15% women of reproductive age and causes several symptoms that result in decreased quality of life and a huge social burden. In recent decades, extracellular vesicles (EVs) have gained attention as a potential therapeutic tool; however, the therapeutic effects of EVs against endometriosis have not been reported. Accordingly, in this study, we investigated the feasibility of nanovesicles (NVs) derived from M1 macrophages (M1NVs) in treating endometriosis. Methods: M1NVs were prepared by serial extrusion. Co-culture assays were performed to investigate changes in tube formation and migration/invasion of eutopic endometrial stroma cells (ESCs) obtained from patients with endometriosis (EM-ESCs). A mouse model of endometriosis was established, and mice were treated with phosphate-buffered saline, M0NVs, or M1NVs to evaluate the efficacy and safety of M1NV for treating endometriosis. Results: M1NVs directly or indirectly inhibited the migration and invasion of EM-ESCs and reduced tube formation. In the mouse model, M1NVs suppressed the development of endometriosis through reprogramming of M2 macrophages, without causing damage to the organs. Conclusions: M1NVs inhibit the development of endometriosis directly, or through repolarizing macrophages from M2 to M1 phenotype. Hence, administration of M1NVs may represent a novel method for the treatment of endometriosis.

Ferroptosis is an iron-dependent programmed cell death process characterised by the accumulation of lethal oxidative damage. Localised iron overload is a unique clinical phenomenon in ovarian endometriosis. However, the role and mechanism of ferroptosis in the course of ovarian endometriosis remain unclear. Traditionally, autophagy promotes cell survival. However, a growing body of research suggests that autophagy promotes ferroptosis under certain conditions. This study aimed to clarify the status of ferroptosis in ovarian endometriosis and explore the mechanism(s) by which iron overload causes ferroptosis and ectopic endometrial resistance to ferroptosis in human. The results showed increased levels of iron and reactive oxygen species in ectopic endometrial stromal cells. Some ferroptosis and autophagy proteins in the ectopic tissues differed from those in the eutopic endometrium. In vitro, iron overload caused decreased cellular activity, increased lipid peroxidation levels, and mitochondrial morphological changes, whereas ferroptosis inhibitors alleviated these phenomena, illustrating activated ferroptosis. Iron overload increased autophagy, and ferroptosis caused by iron overload was inhibited by autophagy inhibitors, indicating that ferroptosis caused by iron overload was autophagy-dependent. We also confirmed the effect of iron overload and autophagy on lesion growth in vivo by constructing a mouse endometriosis model; the results were consistent with those of the in vitro experiments of human tissue and endometrial stomal cells. However, ectopic lesions in patients can resist ferroptosis caused by iron overload, which can promote cystine/glutamate transporter hyperexpression by highly expressing activating transcription factor 4 (ATF4). In summary, local iron overload in ovarian endometriosis can activate autophagy-related ferroptosis in endometrial stromal cells, and ectopic lesions grow in a high-iron environment via ATF4-xCT while resisting ferroptosis. The effects of iron overload on other cells in the endometriosis environment require further study. This study deepens our understanding of the role of ferroptosis in ovarian endometriosis.

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.

To study the efficacy and safety of the dienogest and the gonadotropin-releasing hormone agonist (GnRH-a) in symptomatic females with uterine adenomyosis.A total of 127 patients with adenomyosis wi... 目的：研究地诺孕素和促性腺激素释放激素激动剂（gonadotropin-releasing hormone agonist, GnRH-a）治疗有症状的子宫腺肌病女性患者的疗效和安全性。方法：共招募127例以痛经为主诉的子宫腺肌病患者。第一组每天服用2毫克地诺孕素（DNG）, 第二组服用醋酸戈舍瑞林（GS）（3.6毫克/4周）, 共用12周。12周后进行门诊随访。结果：在127名女性中, D...

The development of endometriosis is closely linked to macrophages, and the type M1 macrophage has been hypothesized to play an inhibitory role in its progression. Escherichia coli induces macrophage polarization toward M1 in numerous diseases and differs in the reproductive tract of patients with and without endometriosis; however, its specific role in endometriosis development remains unknown. Therefore, in this study, E. coli was selected as a stimulator to induce macrophages, and its effects on the growth of endometriosis lesions in vitro and in vivo were investigated using C57BL/6N female mice and endometrial cells. It was revealed that E. coli inhibited the migration and proliferation of co-cultured endometrial cells by IL-1 in vitro and prevented the growth of lesions and induced macrophage polarization toward M1 in vivo. However, this change was counteracted by C-C motif chemokine receptor 2 inhibitors, suggesting that it was associated with bone marrow-derived macrophages. Overall, the presence of E. coli in the abdominal cavity may be a protective factor for endometriosis.