Search Results (18)

Advancements in material science have made biopolymers a reliable solution in treating diseases for which there were no effective treatments. Intrauterine adhesions (IUAs) are the second leading cause of secondary infertility among women of reproductive age. Despite their negative impacts, the available data reveal that there is currently no effective treatment. This work serves to provide an overview of the progress in the biomedical application of biopolymers focusing on the clinical management of IUAs. Hysteroscopic adhesiolysis remains the standard treatment for IUAs, even though it is linked to recurrence and suboptimal reproductive outcomes. Efforts to improve IUAs treatment by combining hysteroscopy with adjuvants like physical barriers have not resulted in better outcomes. Biopolymers like hyaluronic acid (HA) represent a groundbreaking shift in regenerative medicine and have been used as anti-adhesives in the treatment of IUAs. This is attributed to their excellent biocompatibility, cell adhesiveness, biodegradability, low toxicity, and cell growth promotion ability. This study examines naturally occurring biopolymers, underscoring their biomedical applications, and limitations such as poor mechanical properties, rapid degradation, limited residence time, and bioavailability. Drawing from existing evidence and authors’ standpoints, innovative approaches harnessing the power of biopolymer engineering are suggested as future directions to overcome ongoing limitations. Full article

Cellular senescence has emerged as a key mediator in organ-specific fibrosis. Here, we have established the role of endometrial stromal senescence in the progression of endometrial fibrosis, termed intrauterine adhesions (IUA). IUA have significant negative effects on women’s reproductive health and are associated with infertility. We have generated original gene signatures to identify endometrial stromal senescence in single-cell and bulk RNA-sequencing data. By applying generated gene signatures, we revealed an increased level of stromal senescence during the proliferative phase in the endometrium of patients with IUA. Further comparative analysis of cell–cell communications demonstrated that senescent stromal cells in the IUA endometrium create an immunosuppressive and profibrotic microenvironment through an elevated expression of LGALS9. Endometrial stromal senescence persists during the window of implantation and correlates with impaired embryo receptivity of the IUA endometrium. Therefore, stromal senescence can be regarded as a primary cause of an unresponsive endometrium with decreased receptivity and thickness in IUA patients. A LGALS9 immunotherapy protocol, specifically designed to neutralize LGALS9 immunosuppressive activity of senescent cells, may offer a promising opportunity to restore effective immune clearance of these cells within the IUA stroma. Consequently, an LGALS9-based strategy could emerge as a novel therapeutic avenue in the treatment of IUA. Full article

Background: Intrauterine adhesions (IUAs) or Asherman syndrome (AS) represent pathological conditions that affect the endometrium and significantly influence female fertility through a variety of mechanisms. This study aims to identify risk factors, explore pathophysiological mechanisms, diagnostic approaches, and assess how medical background influence the development of these conditions. It also seeks to associate the severity of conditions with clinical outcomes, such as fertility, miscarriages, and menstrual cycle disorders, using American Fertility Society (AFS) scoring system. Materials and methods: This retrospective cohort study included 134 patients aged 18 to 45, who followed hysteroscopy between 2016 and 2024 at two hospitals in Iasi, focusing on those diagnosed with IUAs (102 patients) and AS (32 patients), based on hysteroscopic approach. The exclusions were based of factors like acute uterine bleeding, intrauterine device, obesity and other severe conditions. Results and discussions: Women over 35 years are more likely to develop these conditions due to prior gynaecological procedures which are often associated with fertility issues. Hysteroscopy is established as the gold standard for both diagnosis and treatment, intraoperative diagnosis representing 45.6 % of cases. Amenorrhea is a primary indicator in AS patients (OR = 26.19) and dysmenorrhea as a potential marker for IUAs (OR = 2.67). Patients with IUAs and primary infertility (82.9%) typically have an AFS score 1, corresponding to improved conception rates. Those with AS and primary infertility often present an AFS score 2 (54.5%); patients with AS and secondary infertility were linked to AFS score 3 (58.8%; p = 0.137). Although the incidence of miscarriages is comparable between the two groups, the timing differs: IUAs are predominantly associated with first trimester losses (64.9%), whereas AS is more commonly linked to second trimester miscarriages (45.5%; p = 0.001). Conclusions: The study highlights the necessity of a personalized approach in diagnosing and treating IUAs and AS, considering factors such as age, fertility index, and disease severity. The integration of hysteroscopic techniques with individualized treatment plans based on the patient’s unique medical profile is crucial for adequate management of IUAs and AS. Full article

It is a great challenge to obtain an ideal hydrogel for the clinical treatment of intrauterine adhesion (IUA) disease. Here, a novel injectable chitosan–lignin/poloxamer hydrogel loaded with platelet-rich plasma (CL-PF127@PRP) was prepared by self-assembly at room temperature. Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), rheological analysis, and injectable writing were used to characterize the structure of the hydrogel. The results confirmed that the amino group of chitosan and the sulfonic group of sodium lignosulfonate were ionic-crosslinked by electrostatic attraction, which stabilized the three-dimensional structure of the PF127 hydrogel loaded with PRP, and PRP made the porous structure gradually become tight. Moreover, the CL-PF127@PRP hydrogel displayed good injectability and a solid state. The soaking experiment showed that the CL-PF127@PRP hydrogel had suitable degradation at pH = 7 and a good PRP release rate (PRP release 70% at 96 h). Cell experiments in vitro demonstrated that the CL-PF127@PRP hydrogel possessed good biocompatibility, an anti-inflammatory function, and pro-angiogenic activity. Furthermore, an animal experiment of skin wound and IUA confirmed that the skin wound closure rate of the CL-PF127@PRP hydrogel was over 50% on the seventh day. PRP improved the thickness of the endometrium and uterus receptivity, suggesting that the CL-PF127@PRP hydrogel offers great promise for the clinical treatment of IUA. Full article

Background/Objectives: Intrauterine adhesion (IUA) is characterized by endometrial fibrocyte hyperplasia. The LIN28B gene is associated with many proliferative diseases. However, its association with IUA is entirely unknown. We hypothesized that LIN28B gene polymorphisms are responsible for IUA susceptibility after curettage abortion. Methods: In this genetic association study, We genotyped two common polymorphisms (rs369065 C>T and rs314280 A>G) in 107 patients with IUA and 270 controls without IUA after curettage abortion from a Chinese population between July 2022 and May 2023 and analyzed their associations with IUA risk using multiple logistic regression models. Results: The carriers of genotype rs314280 AA of the LIN28B gene showed an increased risk of IUA (AOR [adjusted odds ratio] = 2.12, 95% CI [confidence interval] = 1.151–3.903), compared to GG+GA genotypes. Further stratification analyses showed that the deleterious role of the rs314280 AA genotype was more evident in patients with fewer than four pregnancies (AOR = 2.740, 95% CI = 1.355–5.540), fewer than two births (AOR = 2.676, 95% CI = 1.300–5.509), and fibrous (AOR = 2.082, 95% CI = 1.084–3.997) and muscular adhesions (AOR = 3.887, 95% CI = 1.116–13.540). However, the rs369065 T>C polymorphism of the LIN28B gene was not significantly associated with the occurrence of IUA. Conclusions: The rs314280 AA genotype of the LIN28B gene is associated with an increased risk of IUA in patients after curettage abortion, especially in those with fewer pregnancies or parities and higher disease severity. Our findings implicate a precise choice of clinical counseling and decision-making of IUA, thereby protecting female reproduction. Full article

The purpose of this study was to explore the effect of Semaglutide on intrauterine adhesions and discover new drugs for such adhesions. In this study, the cell model was simulated by TGF-β1-induced human endometrial epithelial cells, and the animal model was established through mechanical curettage and inflammatory stimulation. After co-culturing with TGF-β1 with or without different concentrations of Semaglutide for 48 h, cells were collected for RT-qPCR and Western blotting analyses. Three doses were subcutaneously injected into experimental mice once a day for two weeks, while the control group received sterile ddH2O. The serum and uterine tissues of the mice were collected. HE and Masson staining were used for the uterine histomorphological and pathological analyses. RT-qPCR and Western blotting were used for mRNA and protein expression analyses. Serum indicators were detected using ELISA kits. The results showed that Semaglutide significantly reduced the mRNA levels of fibrosis indicators ACTA2, COL1A1, and FN and inflammatory indicators TNF-α, IL-6, and NF-κB in the two models. Semaglutide improved endometrium morphology, increased the number of endometrial glands, and reduced collagen deposition in IUA mice. The results also showed that Semaglutide could inhibit vimentin, E-Cadherin, and N-Cadherin in the two models. In summary, Semaglutide can ameliorate fibrosis and inflammation of intrauterine adhesions as well as inhibit epithelial–mesenchymal transition in IUA models. Full article

Intrauterine adhesion (IUA) is primarily caused by endometrial injury, and hysteroscopic adhesiolysis is presently the main treatment. However, postoperative recurrence and poor pregnancy outcomes remain intractable. In this study, we aim to assess the effects of different treatments on clinical symptoms and reproductive outcomes in IUA. This retrospective study was conducted in a tertiary university-affiliated women’s hospital. The study included 1449 consecutive women who desired to have a baby and were diagnosed with IUA through hysteroscopy from January 2016 to December 2021. Patients with IUA underwent hysteroscopic electric resection (E) or cold scissors separation (C), as well as hormone therapy and one or both of the following secondary prevention measures: intrauterine devices (IUD) and hyaluronic acid gel (HA). The pregnancy rate (PR) was significantly higher in the E + IUD + HA (90.23% CI: 85.82, 94.64%) than in other groups (p = 0.000) groups. The rates of full-term birth (p = 0.000) and live birth (p = 0.000) were significantly higher in the E + IUD + HA (67.82% and 68.97%, respectively) and E + HA (62.41% and 63.91%, respectively) groups. Multivariate logistic regression analysis revealed a significantly higher PR in women who received second-look hysteroscopy (OR 1.571, 95% CI: 1.009–2.224, p = 0.013) and E + IUD + HA (OR 4.772, 95% CI: 2.534–8.987, p = 0.000). Combining hysteroscopic electric resection with IUDs and HA gel could prevent adhesion recurrence and improve postoperative pregnancy and live birth outcomes in IUA. Furthermore, postoperative second-look hysteroscopy may increase the PR and shorten the waiting period. Full article

Intrauterine adhesions (IUA) has become one of the main causes of female infertility. How to effectively prevent postoperative re-adhesion has become a clinical challenge. In this study, a mussel-inspired dual-network hydrogel was proposed for the postoperative anti-adhesion of IUA. First, a calcium alginate/polyacrylamide (CA-PAM) hydrogel was prepared via covalent and Ca²⁺ cross-linking. Benefiting from abundant phenolic hydroxyl groups, polydopamine (PDA) was introduced to further enhance the adhesion ability and biocompatibility. This CA-PAM hydrogel immersed in 10 mg/mL dopamine solution possessed remarkable mechanical strength (elastic modulus > 5 kPa) and super stretchability (with a breaking elongation of 720%). At the same time, it showed excellent adhesion (more than 6 kPa). Surprisingly, the coagulation index of the hydrogel was 27.27 ± 4.91, demonstrating attractive coagulation performance in vitro and the potential for rapid hemostasis after surgery. Full article

Intrauterine adhesion (IUA) is a common gynecological disease with limited therapeutic options. Dulaglutide is a long-acting glucagon-like peptide-1 (GLP-1) analog with some anti-fibrotic and anti-inflammatory properties; however, its action on IUA remains uncertain. The purpose of the experiments in this study was to explore the effect of dulaglutide on IUA and to elucidate its mechanism to provide new ideas for the clinical treatment of IUA. An IUA mouse model was established via mechanical curettage and inflammation induction; mice received subcutaneous injection with three doses of dulaglutide once a day for two weeks (treatment) or equal amounts of sterile ddH₂O (control), and sham-operated mice were treated similarly to the control mice. Mice were sacrificed, and uterine tissues were subjected to hematoxylin and eosin (H&E) and Masson’s trichrome staining for histomorphological and pathological analyses and real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting (WB) for gene and protein expression analyses. Dulaglutide improved the shape of the uterine cavity, increased endometrial thickness and the number of glands, and significantly reduced the area of collagen fiber deposition in the endometrium. It significantly reduced collagen type I A 1 (COL1A1), interleukin-1beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), C-C motif chemokine ligand 2 (CCL2), F4/80 (macrophage), vimentin and transforming growth factor-beta (TGF-β) mRNA levels and COL1A1, IL-1β, IL-6, TNF-α, F4/80, vimentin, E-cadherin, TGF-β, and p-Smad2 protein expression levels. This study demonstrates that dulaglutide reduces inflammatory responses by inhibiting M1 macrophage polarization and inflammatory factor release and may ameliorate fibrosis by inhibiting epithelial–mesenchymal transition (EMT) via TGF-β/Smad2 signaling. Full article

The purpose of the present study was to investigate the therapeutic effects of platelet-rich plasma (PRP) in women with moderate to severe intrauterine adhesion (IUA). A retrospective cohort study was conducted at a reproductive medical center between July 2020 and June 2021 to compare the clinical pregnancy rate of two groups (PRP and non-PRP groups) after hysteroscopic adhesiolysis. A multivariate logistic regression analysis and propensity score matching (PSM) were performed to minimize potential bias. According to our inclusion and exclusion criteria, 133 patients were finally enrolled and divided into the PRP group (n = 48) and non-PRP group (n = 85). In the primary comparison, the clinical pregnancy rate in the PRP group was higher than that in the non-PRP group (41.7% vs. 28.2%, p = 0.114), albeit without statistical significance. Multivariate logistic regression analysis was performed, and the results of the adjusted model showed that PRP treatment significantly improved the clinical pregnancy rate (adjusted OR = 3.00, 95% CI = 1.22–7.38, p = 0.017). After PSM, the clinical pregnancy rate was higher in the PRP group than that in the non-PRP group (46.2% vs. 20.5%, p = 0.031). Based on the present study, we concluded that intrauterine perfusion of PRP had great potential in improving the clinical pregnancy rate in patients with moderate to severe IUA. Therefore, we recommend the application of PRP in the treatment of IUA. Full article

Intrauterine adhesion (IUA) causes menstrual disturbance and infertility. There is no effective treatment available for moderate to severe IUA cases. Stem cell-based therapy has been investigated for treating IUA but is limited in clinical applications due to issues including the precise induction of differentiation, tumorigenesis, and unclear molecular mechanisms. In our recent study, we isolated and expanded the long-term cultures of conditional reprogrammed (CR) mouse endometrial epithelial cells. Treating IUA mice with these CR cells (CRCs) restored the morphology and structure of the endometrium and significantly improved the pregnancy rate. In this study, our data with high-throughput sequencing, CRISPR knockout Ihh^−/−CRCs, and transplantation identified for the first time that the Indian hedgehog (Ihh) gene plays a critical role in the regulation of endometrial epithelial cell proliferation. We also found that aberrant activated Ihh-krüppel-like factor 9 (KLF9) signaling contributes to the inhibition of normal progesterone receptor (PR) function in IUA mice. Thus, we hypothesized that inhibition of the Ihh-KLF9 pathway may be a novel strategy to treat IUA. Our data demonstrated that treatment with the hedgehog signaling inhibitor Vismodegib restored the morphology, structure, and microenvironment of the endometrium, and greatly improved the pregnancy rate in IUA mice. This study suggests a promising application of hedgehog inhibitors as a targeted drug in the IUA clinic. Full article

Intrauterine adhesion (IUA) refers to injury to the basal layer of the endometrium, which can be caused by various factors. It is often accompanied by clinical symptoms such as abnormal menstruation, infertility, recurrent abortion, and periodic abdominal pain. In recent years, a number of studies have reported the effects of β-Klotho (KLB) on the occurrence and development of human tumors and fibrotic diseases, but its relationship with endometrial fibroblasts and endometrial fibrosis has not been elucidated. In this study, we compared the expression of KLB in endometrial stromal cells (ESCs) from patients with IUA and normal controls. We constructed animal and cell models of IUA and conducted expression verification and functional experiments on KLB. We found that the expression of KLB was significantly increased in the ESCs of IUA patients and rat models compared with the controls. The overexpression of KLB could promote the proliferation and fibrosis of ESCs. In addition, the overexpression of KLB activated the PI3K/AKT signaling pathway in ESCs. Our study shows that KLB protein is highly expressed in the ESCs of patients with IUA and can enhance stromal cell proliferation and cell fibrosis by activating the PI3K/AKT pathway, thus promoting the development of IUA. Full article

Intrauterine adhesions (IUAs) have caused serious harm to women’s reproductive health. Although emerging evidence has linked intrauterine microbiome to gynecological diseases, the association of intrauterine microbiome with IUA, remains unknown. We performed metagenome-wide association, metabolomics, and transcriptomics studies on IUA and non-IUA uteri of adult rats to identify IUA-associated microbial species, which affected uterine metabolites and endometrial transcriptions. A rat model was used with one side of the duplex uterus undergoing IUA and the other remaining as a non-IUA control. Both 16S rRNA sequencing and metagenome-wide association analysis revealed that instead of Mycoplasmopsis specie in genital tract, murine lung pathogen Mycoplasmopsispulmonis markedly increased in IUA samples and displayed a distinct positive interaction with the host immune system. Moreover, most of the IUA-enriched 58 metabolites positively correlate with M.pulmonis, which inversely correlates with a mitotic progression inhibitor named 3-hydroxycapric acid. A comparison of metabolic profiles of intrauterine flushing fluids from human patients with IUA, endometritis, and fallopian tube obstruction suggested that rat IUA shared much similarity to human IUA. The endometrial gene Tenascin-N, which is responsible for extracellular matrix of wounds, was highly up-regulated, while the key genes encoding parvalbumin, trophectoderm Dkkl1 and telomerase involved in leydig cells, trophectoderm cells, activated T cells and monocytes were dramatically down-regulated in rat IUA endometria. Treatment for rat IUA with estrogen (E2), oxytetracycline (OTC), and a traditional Chinese patent medicine GongXueNing (GXN) did not reduce the incidence of IUA, though inflammatory factor IL-6 was dramatically down-regulated (96–86%) with all three. Instead, in both the E2 and OTC treated groups, IUA became worse with a highly up-regulated B cell receptor signaling pathway, which may be associated with the significantly increased proportions of Ulvibacter or Staphylococcus. Our results suggest an association between intrauterine microbiota alterations, certain uterine metabolites, characteristic changes in endometrial transcription, and IUA and the possibility to intervene in IUA formation by targeting the causal factors, microbial infection, and Tenascin-like proteins. Full article

The paper focuses on the development of a multifractal theoretical model for explaining drug release dynamics (drug release laws and drug release mechanisms of cellular and channel-type) through scale transitions in scale space correlated with experimental data. The mathematical model has been developed for a hydrogel system prepared from chitosan and an antimicrobial aldehyde via covalent imine bonds. The reversible nature of the imine linkage points for a progressive release of the antimicrobial aldehyde is controlled by the reaction equilibrium shifting to the reagents, which in turn is triggered by aldehyde consumption in the inhibition of the microbial growth. The development of the mathematical model considers the release dynamic of the aldehyde in the scale space. Because the release behavior is dictated by the intrinsic properties of the polymer–drug complex system, they were explained in scale space, showing that various drug release dynamics laws can be associated with scale transitions. Moreover, the functionality of a Schrödinger-type differential equation in the same scale space reveals drug release mechanisms of channels and cellular types. These mechanisms are conditioned by the intensity of the polymer–drug interactions. It was demonstrated that the proposed mathematical model confirmed a prolonged release of the aldehyde, respecting the trend established by in vitro release experiments. At the same time, the properties of the hydrogel recommend its application in patients with intrauterine adhesions (IUAs) complicated by chronic endometritis as an alternative to the traditional antibiotics or antifungals. Full article

Intrauterine adhesion (IUA) is caused by artificial endometrial damage during intrauterine cavity surgery. The typical phenotype involves loss of spontaneous endometrium recovery and angiogenesis. Undesirable symptoms include abnormal menstruation and infertility; therefore, prevention and early treatment of IUA remain crucial issues. Extracorporeal shockwave therapy (ESWT) major proposed therapeutic mechanisms include neovascularization, tissue regeneration, and fibrosis. We examined the effects of ESWT and/or platelet-rich plasma (PRP) during preventive and therapeutic stages of IUA by inducing intrauterine mechanical injury in rats. PRP alone, or combined with ESWT, were detected an increased number of endometrial glands, elevated vascular endothelial growth factor protein expression (hematoxylin-eosin staining and immunohistochemistry), and reduced fibrosis rate (Masson trichrome staining). mRNA expression levels of nuclear factor-kappa B, tumor necrosis factor-α, transforming growth factor-β, interleukin (IL)-6, collagen type I alpha 1, and fibronectin were reduced during two stages. However, PRP alone, or ESWT combined with PRP transplantation, not only increased the mRNA levels of vascular endothelial growth factor (VEGF) and progesterone receptor (PR) during the preventive stage but also increased PR, insulin-like growth factor 1 (IGF-1), and IL-4 during the therapeutic stage. These findings revealed that these two treatments inhibited endometrial fibrosis and inflammatory markers, thereby inhibiting the occurrence and development of intrauterine adhesions. Full article