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Adenomyosis (ADS) is a common benign gynecological disease. Abnormal proliferation at the endometrial-myometrial interface (EMI) plays a crucial role in the occurrence and progression of ADS. miR-141-3p is associated with cell proliferation and apoptosis. However, the specific mechanism of miR-141-3p in the etiology of ADS is still unknown. In this study, we explored the effects of miR-141-3p on the proliferation and apoptosis of ADS EMI smooth muscle cells (SMCs). We collected EMI tissues for the primary culture of SMCs from 25 patients diagnosed with ADS and 20 without ADS. Real-time quantitative polymerase chain reaction and western blot were used to measure the mRNA and protein expression levels of miR-141-3p, JAK2, STAT3, phospho-JAK2, and phospho-STAT3 in ADS EMI SMCs. The cell counting kit 8 assay and flow cytometry analysis were used to evaluate the proliferation and apoptosis of EMI SMCs. The miR-141-3p mimic/inhibitor was used to increase or decrease the expression level of miR-141-3p. We added WP1066 to block the phosphorylation of JAK2/STAT3 pathway components. The miR-141-3p levels were decreased, while JAK2 and STAT3 levels were increased in ADS EMI SMCs. miR-141-3p overexpression significantly inhibited the proliferation and enhanced the apoptosis of EMI SMCs, whereas a decrease in miR-141-3p expression level was connected to the opposite results. Meanwhile, inactivated JAK2/STAT3 pathway decreased proliferation and enhanced apoptosis of EMI SMCs after WP1066 treatment. Furthermore, rescue experiments confirmed that the JAK2/STAT3 pathway was the downstream pathway of miR-141-3p and reduced the effect of miR-141-3p on the proliferation and apoptosis of EMI SMCs. These results demonstrate that miR-141-3p regulates the proliferation and apoptosis of ADS EMI SMCs by modulating the JAK2/STAT3 pathway., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Hysteroscopic metroplasty of the uterine septum has been the standard treatment strategy to improve reproductive outcomes, but there are still controversies about the appropriateness of metroplasty. In addition, there have been few studies of the factors related to reproductive outcomes of women after surgery. The study aimed to evaluate the reproductive outcomes and the associated risk factors that influence reproductive outcomes after hysteroscopic metroplasty of women with septate uterus and the desire to conceive., Methods: This study was an observational study. Cases were screened by searching electronic patient files, and demographic factors were collected. We conducted telephone follow-ups to collect the postoperative reproductive outcomes. The primary outcome of this study was live birth, and secondary outcomes were ongoing pregnancy, clinical pregnancy, early miscarriage, and preterm birth. Demographic variables included patients' age, body mass index (BMI), the type of septum, infertility and miscarriage history, and complications including intrauterine adhesions, endometrial polyps, endometriosis, and adenomyosis were collected to perform univariate and multivariate analyses to predict the risk factors of reproductive outcomes after surgery treatment., Results: In total, 348 women were evaluated and followed up. There were 95 cases (27.3%, 95/348) with combined infertility, 195 cases (56.0%, 195/348) with miscarriage history, and cases combined with intrauterine adhesions, endometrial polyps, endometriosis, and adenomyosis were 107 (30.7%, 107/348), 53 (15.2%, 53/348), 28 (8.0%, 28/348), and 5 (1.4%), respectively. Following surgery, the live birth rate and clinical pregnancy rate were significantly higher than prior to surgery (84.6% vs 3.7%, p = 0.000; and 78.2% vs 69.5%, p = 0.01, respectively), early miscarriage rate and preterm delivery rate were significantly lower (8.8% vs 80.6%, p = 0.000; and 7.0% vs 66.7%, p =0.000, respectively). After adjusting for body mass index, miscarriage history, and complications, multivariable logistic regression analysis revealed age ≥ 35 years and primary infertility as independent factors that affected postoperative clinical pregnancy (OR 4.025, 95% CI 2.063-7.851, p = 0.000; and OR 3.603, 95% CI 1.903-6.820, p = 0.000; respectively) and ongoing pregnancy (OR 3.420, 95% CI 1.812-6.455, p = 0.000; and OR 2.586, 95% CI 1.419-4.712, p = 0.002; respectively)., Conclusions: Hysteroscopic metroplasty could lead to improved reproductive outcomes of women with septate uterus. Both age and primary infertility were independent factors for postoperative reproductive outcomes., Trial Registration: Chi ECRCT20210343., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chang, Shen, Wang, Guo and Duan.)

Background: Uterine adenomyosis is associated with chronic pelvic pain, abnormal uterine bleeding, and infertility. The pathogenesis of adenomyosis is still unclear. Circular RNAs (circRNAs) have been implicated in several benign diseases and malignant tumors. We aimed to explore the co-dysregulated circular RNA profile in the eutopic endometrium and endometrial-myometrial interface (EMI) of adenomyosis., Methods: Total RNA was extracted from the eutopic endometrium and EMI of 5 patients with adenomyosis and 3 patients without adenomyosis. Next-generation sequencing was performed to identify the circRNA expression profile of the two tissue types. Bioinformatics analysis was performed to predict circRNA-binding miRNAs and miRNA-binding mRNAs and construct ceRNA networks, and functional enrichment analysis was performed to predict the biological functions of circRNAs., Results: Among the adenomyosis patients, 760 circRNAs were significantly upregulated and 119 circRNAs were significantly downregulated in the EMI of adenomyosis, while 47 circRNAs were significantly upregulated and 17 circRNAs were significantly downregulated in the eutopic endometrium of adenomyosis. We identified hsa_circ_0002144 and hsa_circ_0005806 as co-upregulated and hsa_circ_0079536 and hsa_circ_0024766 as co-downregulated in the eutopic endometrium and EMI. Bioinformatics analysis was performed to construct a ceRNA network of codifferentially expressed circRNAs. The MAPK signaling pathway is the most important signaling pathway involved in the function of the ceRNA network., Conclusions: Co-dysregulated circRNAs were present in the eutopic endometrium and EMI of adenomyosis. MiRNA binding sites were observed for all of these circRNAs and found to regulate gene expression. Co-dysregulated circRNAs may induce the eutopic endometrial invagination process through the MAPK signaling pathway and promote the progression of adenomyosis., (© 2022. The Author(s).)

Background: The denomyotic junctional zone (JZ) plays an important role in the pathogenesis of adenomyosis. Proliferating cell nuclear antigen (PCNA) is an important nuclear marker of cell proliferation. This study aimed to evaluate the effects of the cannabinoid receptor CB1 on proliferation and apoptosis in the JZ in women with and without adenomyosis., Methods: JZ smooth muscle cells (JZSMCs) of the adenomyosis and control groups were collected and cultivated. Immunohistochemistry and immunoblotting were used for protein localization and expression detection of CB1 and PCNA. Additionally, qRT-PCR was used to quantitatively analyse the mRNA expression of the two. AM251 and ACEA were used to regulate the function of CB1 receptors, and CCK-8 assay and flow cytometry assay were used to verify the proliferation and apoptosis of JZSMCs after regulation., Results: We demonstrated that in normal JZSMCs CB1 and PCNA messenger RNA (mRNA) and protein expression was significantly higher in the proliferative phase of the menstrual cycle than in the secretory phase. CB1 and PCNA expression in JZSMCs from women with ADS was significantly higher than that in control women and did not significantly differ across the menstrual cycle. CB1 receptor antagonist AM251 inhibited the proliferation of adenomyotic JZSMCs in a dose-dependent manner. The CB1 receptor agonist ACEA significantly promoted the proliferation of adenomyotic JZSMCs. The apoptosis rate of adenomyotic JZSMCs treated with AM251 was significantly higher than that of JZSMCs from the untreated control group. The apoptosis rate was significantly decreased in the ACEA group compared with that in the untreated control group. Furthermore, AM251 suppressed the phosphorylation of AKT and Erk1/2 in adenomyotic JZSMCs. The CB1 agonist ACEA significantly promoted the phosphorylation of AKT and Erk1/2., Conclusions: Our results indicated that the levels of CB1 and PCNA were increased in patients with adenomyosis and that cyclic changes were lost. CB1 may affect uterine JZ proliferation and apoptosis in adenomyosis by enhancing AKT and MAPK/Erk signalling.