Endometrial Tissue Research Articles

Expression and clinical significance of lncRNA PART1 in patients with unexplained recurrent pregnancy loss

Purpose Previous studies have reported the involvement of long noncoding RNAs (lncRNAs) in reproductive diseases via the regulation of target genes. This study aimed to determine whether lnc-prostate androgen-regulated transcript 1 (lnc-PART1)could be used as a biomarker of unexplained recurrent pregnancy loss (URPL) and a possible predictor of poor pregnancy outcomes in women with URPL. Materials and methods Sixty patients with URPL and 15 healthy women were included in this study. PART1 expression was detected in plasma and endometrial tissues using a quantitative reverse transcription polymerase chain reaction. Logistic regression and receiver operating characteristic curve analyses were performed to analyze the association between PART1 expression and pregnancy outcomes in women with URPL. Results The expression of PART1transcript variant 2 was significantly up-regulated in the endometrial specimens from patients with URPL compared to control tissues. High tissue expression levels of PART1transcript variant 2 were associated with poor pregnancy outcomes in women with URPL, indicating that it could serve as a potential risk factor. Additionally, PART1 could serve as a potential risk factor for adverse pregnancy outcomes in patients with URPL (OR = 4.374; 95% CI = 1.052–18.189; p = .042). Conclusion lncRNA PART1 transcript variant 2 was highly expressed in patients with URPL. Therefore, it is important to conduct in-depth studies on the relationship between PART1 expression and URPL.

Nicotinamide Mononucleotide Improves Endometrial Homeostasis in a Rat Model of Polycystic Ovary Syndrome by Decreasing Insulin Resistance and Regulating the Glylytic Pathway.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that can lead to insulin resistance (IR) and dysregulation of glucose metabolism, resulting in an imbalance in the endometrial environment, which is unfavorable for embryo implantation of PCOS. This study aims to investigate whether nicotinamide mononucleotide (NMN) improves the stability of the endometrium in a rat model of PCOS and identifies whether it is related to reduce IR and increase glycolysis levels and its potential signaling pathway. Female Sprague-Dawley (SD) rats are fed letrozole and a high-fat diet (HFD) to form the PCOS model, then the model rats are treated with or without NMN. It randomly divided into control, PCOS, and PCOS-NMN groups according to the feeding and treating method. Compared with the PCOS group, the regular estrous cycles are restored, the serum androgen (p<0.01) and fasting insulin levels (p<0.05) are reduced, and endometrial morphology (p<0.05) is improved in NMN-PCOS group. Furthermore, NMN inhibits endometrial cell apoptosis, improves endometrial decidualization transition, reduces IR, restores the expression of glycolysis rate-limiting enzymes, and activates the PI3K/AKT pathway in the uterus. These results suggest that NMN enhances endometrial tissue homeostasis by decreasing uterine IR and regulating the glycolysis through the PI3K/AKT pathway.

The mechanism of wen jing tang in the treatment of endometriosis: Insights from network pharmacology and experimental validation

BackgroundEndometriosis (EM) is a hormone-dependent condition marked by progressively severe secondary dysmenorrhea, significantly impacting patients' quality of life and overall health. Wen Jing Tang (WJT), a traditional Chinese medicinal formulation derived from the Synopsis of the Golden Chamber, has proven to be an effective therapeutic agent for EM. However, the precise molecular mechanisms underlying its efficacy remain unclear. ObjectiveThis study aims to elucidate the underlying mechanisms of WJT in the treatment of EM by integrating network pharmacology analysis with experimental validation. MethodsThe chemical constituents and target sites of WJT were obtained from the TCMSP database, while EM-related target genes were sourced from OMIM, TTD, GeneCards, and the DrugBank databases. A "herbs-components-targets" network was constructed using Cytoscape 3.9.1. The intersecting target genes of WJT and EM were then uploaded to the STRING database for protein-protein interaction (PPI) analysis. Subsequently, the common target genes were subjected to GO and KEGG enrichment analysis via the DAVID database. Molecular docking were employed to analyze the binding affinities between the top five core components and their respective targets. Additionally, ELISA were used to quantify the serum levels of IL-6, IL-1β, E2, and P in EM model rats. The expression levels of TNF-α, HIF1A, STAT3, and EGFR mRNA and proteins in ectopic endometrial tissue were assessed using q-PCR and Western blotting. ResultsA total of 250 chemical components and 553 targets were identified in WJT, while 3491 EM-related targets were screened from multiple databases. Among these, 187 common targets between WJT and EM were found, with quercetin, kaempferol, and beta-sitosterol emerging as the core chemical components, and AKT1, IL6, TNF, and IL1B identified as the key targets. These core components demonstrated strong binding affinities to the targets. GO and KEGG enrichment analyses revealed that the shared targets were primarily involved in the HIF1 signaling pathway. Furthermore, compared to the control group, the EM model rats exhibited an increased ectopic endometrial area, disordered glandular and stromal cells, and notable inflammatory infiltration. Serum levels of IL-6, IL-1β, E2, and P were significantly elevated (P < 0.01), and the expression of TNF-α, HIF1A, STAT3, and EGFR in the ectopic endometrium was markedly increased (P < 0.01). Following WJT intervention, the ectopic endometrial area in model rats was reduced, the morphology and structure of the endometrial cells showed improvement, and serum levels of IL-6, IL-1β, E2, and P were significantly decreased (P < 0.05). WJT also inhibited the expression of HIF1 pathway-related proteins TNF-α, HIF1A, STAT3, and EGFR (P < 0.05). ConclusionThe mechanism by which WJT prevents and treats EM may involve the reduction of inflammation through the inhibition of the HIF1 signaling pathway.

Reduced expression of SMAD7 and consequent reduction of autophagy promotes endometrial stromal-myofibroblast transition and fibrosis.

Abnormal autophagy and the transforming growth factor-β (TGFβ)-SMAD3/7 signaling pathway play an important role in the development of intrauterine adhesions (IUA); however, the exact underlying mechanisms remain unclear. In this study, we used IUA patient tissue and SMAD7 conditional knockout mice to detect whether SMAD7 effected IUA via regulation of autophagy and the TGFβ-SMAD3 signaling pathway. We applied a combination of techniques for detection of p-SMAD3, SMAD7, autophagy and fibrosis-related proteins, autophagic flux and analysis of the SMAD3 binding site. Endometrial tissue of patients with IUA exhibited lower expression levels of SMAD7. In endometrial stromal cells, silencing of SMAD7 inhibited autophagic flux, whereas overexpressed SMAD7 promoted autophagic flux. This SMAD7-mediated autophagic flux regulates the stromal-myofibroblast transition, and these phenotypes were regulated by the TGFβ-SMAD3 signaling pathway. SMAD3 directly binds to the 3'-untranslated region of transcription factor EB (TFEB) and inhibits its transcription. SMAD7 promoted autophagic flux by inhibiting SMAD3, thereby promoting the expression of TFEB. In SMAD7 conditional knockout mice, the endometria showed a fibrotic phenotype. Simultaneously, autophagic flux was inhibited. On administering the autophagy activator rapamycin, this endometrial fibrosis phenotype was partially reversed. The loss of SMAD7 promotes endometrial fibrosis by inhibiting autophagic flux via the TGFβ-SMAD3 pathway. Therefore, this study reveals a potential therapeutic target for IUA.

Endometrial pattern in women with abnormal uterine bleeding attending a tertiary care centre of Kathmandu

Background: Abnormal uterine bleeding is one of the most common problems among pre and postmenopausal women. Abnormal uterine bleeding is diagnosed when there is a substantial change in frequency, duration, or amountof bleeding during or between periodsin the absence of any organic pathology. The study was perform to assess the endometrial causes of abnormal uterine bleeding and their incidence in different age groups. Materials and methods: It was a cross sectional and descriptive study carried out at a Manmohan medical College &amp; hospital, over a period of two year from 13th April, 2020 to 15th March, 2022. In the study all the endometrial tissue either obtained by endometrial curettage and biopsy or hysterectomy presenting with abnormal uterine bleeding for more than 3 months were included Results: A total of 88 cases were received during this period, out of which there were 78 endometrial tissue samples and 10 hysterectomy specimens. The patient’s age ranged from 20 years to 73years. The pattern of endometrial biopsy are Proliferative (37.5%) and secretory (20.45%) phase endometrium is the most common pattern seen, followed by disordered proliferative endometrium (13.63%), endometrial hyperplasia without atypia (9.09%), Change consistent with Exogenous Hormone (5.68%), Chronic Endometritis (5.68%), Endometrial Polyp(3.40%), Endometrial Hyperplasia with Atypia(2.27%) and Endometrial Carcinoma (2.27%). Conclusions: Patients with abnormal uterine bleeding show a varying spectrum of endometrial pattern. Cyclic endometrium is commonly seen in the reproductive age group whereas hyperplasia and carcinomas are seen in pre/postmenopausal age group. Endometrial biopsy with histopathological examination is a major diagnostic tool in the evaluation of abnormal uterine bleeding.

Clear Cell Carcinoma Arising in Vaginal Endometriosis in a Patient 33 Years after Total Hysterectomy and Bilateral Salpingo-oophorectomy: A Case Report

Abstract Introduction/Objective Endometriosis, a common gynecological disorder characterized by ectopic endometrial tissue, is associated with an increased risk of extraovarian malignancies. Vaginal endometriosis is a rare condition, and the occurrence of vaginal malignancies arising from endometriosis is anticipated to be exceedingly rare. Here, we present a rare case of clear cell carcinoma arising in vaginal endometriosis, occurring three decades post-total hysterectomy and bilateral salpingo-oophorectomy. Methods/Case Report A 71-year-old female presented with abnormal Cologuard results, leading to a colonoscopy revealing a mass in the recto-sigmoid colon. She had undergone total hysterectomy and bilateral salpingo- oophorectomy for leiomyoma and endometriosis 33 years prior. Histopathological examination revealed clear cell carcinoma arising in vaginal endometriosis, with tumor extension through the colon wall to the colonic mucosal surface (Figure 1). Notably, the vaginal mucosal surface was negative for tumor. Immunohistochemistry staining demonstrated positivity for Pax8, CK7, AE1/3, racemase, and p16, while negtive for ER, PR, CDX2, CK20, CAIX, SatB2, RCC, WTI, Napsin, and calretinin (Figure 2). The staining for p53 was patchy (wild type, not mutated). Cancer-type relevant biomarkers reveal BRAF mutation (p.D594G), ARID1A mutation (p.M1564fs), PD-L1 mutation (Positive, CPS:80), and PIK3CA mutation (p.H1047L). The histologic and immunohistochemistry findings are consistent with clear cell carcinoma arising in a long-standing area of endometriosis (previous surgery in 1990). Results (if a Case Study enter NA) NA Conclusion Clear cell adenocarcinoma arising from endometriosis is exceptionally rare. Pathologists must consider the possibility of tumors arising from endometriosis when evaluating bowel or mesenteric neoplasms, even decades post-total hysterectomy and bilateral salpingo-oophorectomy. Immunohistochemistry plays a crucial role in the differential diagnosis between carcinoma arising from endometriosis and primary colonic carcinoma. Additionally, Sampson’s criteria are valuable for diagnosing malignant transformations in endometriosis. The identification of specific cancer-type relevant biomarkers, such as BRAF, ARID1A, PD-L1, and PIK3CA mutations, provides additional insights into the molecular characteristics of the tumor, which may have implications for prognosis and treatment selection.

Stress-induced phosphoprotein 1 expression in the endometrium and myometrium of patients with adenomyosis

BACKGROUND: The study of stress-induced phosphoprotein 1 in the pathogenesis of adenomyosis is not only of theoretical interest, but this protein may be also considered as a potential biomarker of the disease. AIM: The aim of this study was to evaluate stress-induced phosphoprotein 1 expression in the endometrium and heterotopic foci in women with isolated adenomyosis and in combination with benign hyperproliferative diseases of the reproductive organs. MATERIALS AND METHODS: This study enrolled 66 women aged 21 to 47 years (34.9 ± 6.7 years), including 49 patients with adenomyosis and 17 women in the control group. The main group was divided into subgroups depending on the concomitant hyperproliferative disease such as isolated adenomyosis (n = 36), adenomyosis combined with uterine fibroids (n = 8), and adenomyosis combined with endometriosis (n = 5). The patients underwent endometrial biopsy and multifocal myometrial biopsy. Histological and immunohistochemical studies were performed to assess stress-induced phosphoprotein 1 expression in the glandular and stromal components of the endometrium and ectopic endometrial tissue within the uterine myometrium. RESULTS: We found increased stress-induced phosphoprotein 1 expression in the adenomyosis lesion compared to that in the myometrium of the control group, regardless of the phase of the menstrual cycle (p 0.001). When studying stress-induced phosphoprotein 1 expression in the endometrium of the main group in the proliferative phase of the menstrual cycle, an increase was found, but the differences were not significant. Stress-induced phosphoprotein 1 expression in the secretory phase of the menstrual cycle was higher in the glandular component of the endometrium of patients with adenomyosis compared to the levels in women in the control group (p 0.05). CONCLUSIONS: The increased expression of stress-induced phosphoprotein 1 in the glandular component of the adenomyosis lesion indicates a potential role of the protein in the pathogenesis of the disease. However, further research is needed to determine its practical significance.

Dysregulated miR-124-3p in endometrial epithelial cells reduces endometrial receptivity by altering polarity and adhesion

The endometrium undergoes substantial remodeling in each menstrual cycle to become receptive to an implanting embryo. Abnormal endometrial receptivity is one of the major causes of embryo implantation failure and infertility. MicroRNA-124-3p is elevated in both the serum and endometrial tissue of women with chronic endometritis, a condition associated with infertility. MicroRNA-124-3p also has a role in cell adhesion, a key function during receptivity to allow blastocysts to adhere and implant. In this study, we aimed to determine the function of microRNA-124-3p on endometrial epithelial adhesive capacity during receptivity and effect on embryo implantation. Using a unique inducible, uterine epithelial-specific microRNA overexpression mouse model, we demonstrated that elevated uterine epithelial microRNA-124-3p impaired endometrial receptivity by altering genes associated with cell adhesion and polarity. This resulted in embryo implantation failure. Similarly in a second mouse model, increasing microRNA-124-3p expression only in mouse uterine surface (luminal) epithelium impaired receptivity and led to implantation failure. In humans, we demonstrated that microRNA-124-3p was abnormally increased in the endometrial epithelium of women with unexplained infertility during the receptive window. MicroRNA-124-3p overexpression in primary human endometrial epithelial cells (HEECs) impaired primary human embryo trophectoderm attachment in a 3-dimensional culture model of endometrium. Reduction of microRNA-124-3p in HEECs from infertile women normalized HEEC adhesive capacity. Overexpression of microRNA-124-3p or knockdown of its direct target IQGAP1 reduced fertile HEEC adhesion and its ability to lose polarity. Collectively, our data highlight that microRNA-124-3p and its protein targets contribute to endometrial receptivity by altering cell polarity and adhesion.

Metformin reverses infertility in a mouse model of endometriosis: unveiling disease pathways and implications for future clinical approaches

Research QuestionDoes metformin reverse endometriosis-associated infertility? DesignEndometriosis was induced by transplanting endometrial tissue fragments from B6CBAF1 mice into the same strain female recipients. Mice were divided into groups: Endometriosis-End (n=24), Sham-operated (n=12), Endometriosis with orally administrated metformin during 3 months (0,5mg/ml)-EndMet (n=21), and Sham-operated metformin-treated-ShamMet (n=16). Half of mice per group was used for fertility studies. Implant growth was monitored by ultrasound and serum estradiol, glucose, and cholesterol (total, LDL, HDL) levels were assessed. Fibrosis was quantified in Masson's trichrome-stained sections of eutopic-Eu and ectopic-Ec endometrial tissue by computer-assisted analysis. PCNA, CYP17a1, F4/80 and galectin-3 were analyzed by immunofluorescence and Western blotting; NFkB, GPX-1 and HO-1 only by Western blotting. Statistical significance was set at p<0.05. ResultsThe endometriosis model was successfully established. End animals showed lower fertility rates than sham-operated mice, whereas metformin treatment increased the number of fetuses per pregnant mouse, restoring fertility to control levels, besides reducing implant growth and vascularization. Ectopic endometrial tissue resembled eutopic counterpart but showed increased PCNA levels and fibrosis that decreased after metformin treatment. PCNA expression decreased in pregnant mice. Metformin diminished CYP17a1 expression in EuEnd and on the contrary upregulated F4/80, galectin-3, NFkB and antioxidant enzymes, HO-1 and GPX-1, in non-mated mice. ConclusionsThese results emphasize metformin's application, even in a subtherapeutic dose, to alleviate oxidative stress and to mitigate endometriosis lesions fibrosis in a murine model of endometriosis. The study highlights metformin's potential as a pharmacological intervention for improving infertility in endometriosis, reinforcing its promising contribution to reproductive health.

First detection and impact of bovine herpesvirus type 4 on dairy cattle reproduction in Thailand

Background and Aim: Postpartum reproductive tract infections pose significant challenges to dairy farms, leading to economic losses due to reduced fertility associated with uterine inflammation. In veterinary practice, numerous research groups have explored the underlying causes of subfertility in cows, including surveying endemic viral infections related to endometritis in local areas. This study investigated bovine herpesvirus 4 (BoHV-4) infection in Thai dairy herds and assessed its impact on endometritis and subsequent reproductive outcomes. Materials and Methods: The present study analyzed BoHV-4 DNA in various samples, including milk, blood, and endometrial tissue, from 44 Holstein-Friesian cows 21–47 days postpartum across five dairy herds in Central Thailand. BoHV-4 glycoprotein B and thymidine kinase DNA sequences were detected using the polymerase chain reaction (PCR) and nested PCR, with sequence comparisons made to GenBank data for phylogenetic analysis. The endometritis status was diagnosed through vaginal mucus examination and endometrial cytology, with reproductive performance monitored up to the subsequent calving. Results: BoHV-4 DNA was identified in blood and endometrial tissues (15.91%) but not in milk samples. Phylogenetic analysis revealed that the local BoHV-4 strains are similar to those identified in Brazil and Japan. Notably, the presence of BoHV-4 was correlated with reduced postpartum reproductive performance, particularly extending the interval from calving to the first service. Conclusion: Our findings underscore the importance of integrating BoHV-4 genomic surveys and uterine health assessments to refine reproductive management strategies within the dairy industry. Keywords: bovine herpesvirus-4, dairy cattle, endometritis, phylogenetic analysis, reproductive performance, Thailand.

Elevated MMP-9, Survivin, TGB1 and Downregulated Tissue Inhibitor of TIMP-1, Caspase-3 Activities are Independent of the Low Levels miR-183 in Endometriosis.

This study aimed to measure the correlation between miR-183 and gene expression that regulates apoptosis and adhesion mechanism that may be linked to the pathogenesis of endometriosis. Forty-four subjects, including 22 control subjects, participated in this study. We collected ectopic endometriosis and endometrial samples. For the control, the sample was taken from endometrial tissue through pipelle biopsy. RNA was extracted from all tissues using RNA mini kit, and the expression was assessed using quantitative-real time PCR. Relative mRNA and miRNA expression were presented using the formula of the Livak method. The data were statistically analyzed using GraphPad Prism 8. The expression of Caspase-3, Survivin, Integrin β1 (ITGB1), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) (adhesion- and apoptosis-related gene) were calculated using the relative expression method. We found significant differences in Caspase-3, Survivin, ITGB1, MMP-9, and TIMP-1 expression between ectopic endometriosis tissues of women with endometriosis compared to healthy endometrium. MMP-9, Survivin, and ITGB1 was significantly increased in the endometriosis group, while Caspase-3, TIMP-1, and miR-183 were significantly reduced in the endometriosis group. No correlation was found between the expression level of miR-183 and Caspase3, Survivin, ITGB1, and Cadherin in both tissue types. Despite the difference in expression levels of miR-183 and associated adhesion- and apoptosis-related genes, there was no significant association between miR-183 with specific adhesion and apoptosis genes in endometriosis tissue.

Exploring the role of endoplasmic reticulum stress in recurrent spontaneous abortion: Identification of diagnostic biomarkers and immune cell interactions

Dysregulated endoplasmic reticulum stress (ERS) is associated with recurrent spontaneous abortion (RSA) and is involved in the mechanisms that govern immune balance and vascular regulation at the maternal-fetal interface. The molecular intricacies of these mechanisms remain elusive. This study employed microarray and bioinformatics techniques to examine genetic abnormalities in endometrial tissues from RSA patients, with the objective of identifying potential ERS-related biomarkers. By integrating two publicly available microarray datasets, consisting of 88 RSA and 42 control samples, we conducted an extensive analysis, including differential expression, functional annotation, molecular interactions, and immune cell infiltration. Analysis of immune cell characteristics suggests an inflammatory immune imbalance as a potential contributor to RSA progression. Both innate and adaptive immunity were found to play roles in RSA development, with M1 macrophages constituting a significant proportion of immune infiltration. We identified five key ERS-associated genes (TMEM33, QRICH1, MBTPS2, ERN1, and BAK1) linked to immune-related mechanisms, with RT-qPCR results aligning with bioinformatics findings. Our research findings offer a fresh and comprehensive perspective on the ERS-related genes' pathways and interaction networks, offering significant insights for the advancement of innovative therapy techniques for RSA.

Tertiary lymphoid structures in endometriosis

To determine whether tertiary lymphoid structures (TLSs), which reflect organized immune cell aggregates present in non-lymphoid tissues, are consistent features of endometriosis lesions. Detailed histopathological analysis of endometrial and lesion tissue from endometriosis patients and controls was performed. Multiplex immunofluorescence on select samples was then conducted to identify canonical cell populations present within TLSs: CD3+ and CD8+ T-cells, CD79a+ B-cells, CD208+ dendritic cells, CD21+ follicular dendritic cells (fDC), and PNAd+ high endothelial venules (HEVs). Histologically confirmed endometriosis patients (N=113; 44.3± 6.0) and control individuals (N=110; 44.6±7.1). Not applicable. Detection of TLSs as characterized by the presence of all canonical cell types that constitute TLS and structure morphology. Of the selected samples (N=18; 6 ectopic/eutopic/control), mature TLSs were identified in 3 ectopic tissue samples present on the ovary and fallopian tube, with immature TLSs (lacking fDC networks and HEVs) present throughout eutopic and control endometrial samples. These findings demonstrate the presence of TLSs across various endometriosis phenotypes, prompting further research into their significance within disease pathophysiology and the prognostic implications for patients.

RNA sequencing reveals molecular mechanisms of endometriosis lesion development in mice.

Understanding of molecular mechanisms contributing to the pathophysiology of endometriosis, and upstream drivers of lesion formation, remains limited. Using a C57Bl/6 mouse model in which decidualized endometrial tissue is injected subcutaneously in the abdomen of recipient mice, we generated a comprehensive profile of gene expression in decidualized endometrial tissue (n=4), and in endometriosis-like lesions at Day 7 (n=4) and Day 14 (n=4) of formation. High-throughput mRNA sequencing allowed identification of genes and pathways involved in the initiation and progression of endometriosis-like lesions. We observed distinct patterns of gene expression with substantial differences between the lesions and the decidualized endometrium that remained stable across the two lesion timepoints, and showed similarity to transcriptional changes implicated in human endometriosis lesion formation. Pathway enrichment analysis revealed several immune and inflammatory response-associated canonical pathways, multiple potential upstream regulators, and involvement of genes not previously implicated in endometriosis pathogenesis, including IRF2BP2 and ZBTB10, suggesting novel roles in disease progression. Collectively, the provided data will be a useful resource to inform research on the molecular mechanisms contributing to endometriosis-like lesion development in this mouse model.

Endometriotic lesions and their recurrence: A Study on the mediators of immunoregulatory (TGF-β/miR-20a) and stemness (NANOG/miR-145)

Endometriosis is a common estrogen-dependent disease that involves various cellular processes. Additionally, miRNAs play a crucial role in the development of the disease as an important component of the microenvironment. In this study, tissue specimens of eutopic and ectopic lesions of 20 women, whose endometriosis was later approved by the pathology laboratory, were biopsied through laparoscopy. As a control group, endometrial tissue specimens were collected from 20 women who underwent curettage for reasons unrelated to endometriosis. The expression levels of miR-20A and miR-145 and their target genes, TGF-β and NANOG, were measured in these samples as markers of stemness and immunomodulatory properties, respectively. The study also aimed to compare the expression levels of target genes and miRNAs in ectopic lesions regarding endometriosis recurrence post-surgery. The study revealed that the expression of TGF-β and NANOG genes was significantly upregulated in endometriotic tissues compared to the control group. There was also a notable increase in miR-20A and miR-145 expression in the endometriotic tissues compared to the control group. While there was no significant correlation between the expression of miR-20a and TGF-β, we observed a negative correlation between the expression level of miR-145 and NANOG. Additionally, the ROC curve analysis emphasized miR-14 as a potential biomarker for endometriosis over miR-20a. However, our findings on disease recurrence underscore the importance of miR-20a in the early detection of endometriosis recurrence.

Mayer-Rokitansky-Küster-Hauser Syndrome: A Case of Primary Amenorrhoea and Diagnostic Approach

Background: Amenorrhoea, defined as the absence of menstruation, can be classified into primary and secondary types. Primary amenorrhoea is diagnosed when menstruation has not occurred by age 15 or within three years of breast development. Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a rare cause of primary amenorrhoea characterized by uterovaginal aplasia in women with a normal 46, XX karyotype and secondary sexual characteristics. This case report discusses a 15-year-old girl diagnosed with MRKH syndrome after a thorough diagnostic workup. Methods: A detailed diagnostic evaluation was conducted, including physical examination, imaging (ultrasonography and MRI), hormonal testing, and chromosomal analysis. The patient presented with primary amenorrhoea and no family history of related conditions. Ultrasound and MRI confirmed the absence of a uterus and non-visualization of the ovaries. Hormonal tests were within normal ranges, and chromosomal analysis revealed a 46, XX karyotype. Results: The diagnostic workup confirmed an atrophic uterus with small bilateral ovaries and no functional endometrial tissue. Mayer-Rokitansky-Küster-Hauser syndrome was diagnosed. The patient was counseled regarding surgical options, including neovaginoplasty, to create a functional vaginal canal for sexual intercourse. Conclusion: MRKH syndrome, though rare, is an important consideration in cases of primary amenorrhoea. Timely diagnosis through imaging and chromosomal analysis is crucial for appropriate management. Psychological counseling and surgical options such as neovaginoplasty can significantly improve the quality of life for affected individuals, particularly regarding sexual health and reproductive possibilities. Addressing the psychological burden associated with infertility is also critical to patient care.

TLR-2 and TLR-4 mRNA expression in different grades of histopathological lesions of equine endometrium from follicular phase.

Increased synthesis and deposition of collagen(COL) in the extracellular matrix (ECM) of equine endometrium contributes to endometrosis. Toll-like receptors (TLRs) are transmembrane receptors involved in the innate immune response, recognized for their role in antigen recognition and previously associated with equine endometritis. The TLRs not only recognize pathogen-associated molecular patterns but also regulate inflammations, fibrosis and cancer. The aim of this study was to explore the relationship between TLR expression at different stages of Kenney and Doig's (K-D) grading and COL1 expression during the follicular phase of the oestrous cycle. Forty samples of endometrial tissues were collected post-mortem from mares on the follicular phase of the oestrous cycle (10 samples of each K-D category). Relative mRNA transcription of TLR-2, TLR-4 and COL1A2 genes was assessed using qPCR, and COL1 protein expression by Western blot analysis. The COL1A2 transcription increased in category IIB when compared to categories I, IIA and III endometria (p < .01). The relative protein abundance of COL1 showed no significant differences between endometrial categories (p > .05). As for the TLRs mRNA transcription, TLR-2/-4 transcripts increased in IIA when compared to the other K-D endometria categories (p < .05). Our findings suggest that TLRs may be involved in the initiation of the endometrial inflammatory response. Additional studies are needed to explore TLRs' potential role as diagnostic markers for monitoring inflammation progression and fibrosis development, as well as their involvement in the mechanisms underlying fibrotic pathways.

A Retrospective Study on the Expression of E-Cadherin in Endometrial Carcinoma.

E-cadherin is a cell adhesion molecule crucial for maintaining cellular integrity and survival. E-cadherin is the focus of this study, which aims to evaluate its immunohistochemical staining patterns in endometrial carcinoma (EC). Material and methods In this retrospective study, 25 formalin-fixed, paraffin-embedded tissue blocks of EC were retrieved from the Department of Pathology at Saveetha Medical College. These samples, collected between September 2020 and May 2023, were identified using unique histopathology numbers. Results The analysis revealed that E-cadherin expression decreased as the endometrial tissue progressed from normal to carcinoma. This reduction was more pronounced in cancers with greater depth of invasion and in more advanced stages compared to those with less invasive depth and earlier stages. Additionally, E-cadherin expression was higher in grade 1 tumors but became heterogeneous or negative in grade 3 tumors. Conclusion The downregulation of E-cadherin is likely due to disruptions in the cadherin-catenin complex, which is linked to the potential for local and distant metastasis in cancer. This study underscores the significance of cell adhesion molecule expression in predicting the prognosis of EC.

Network-based pharmacology and experimental validation to explore the mechanism of action of the Jiawei Pentongling formula for the treatment of endometriosis-related pain.

To investigate the effects and mechanisms of the Jiawei Pentongling formula (, JWPTL) in treating endometriosis-related pain using network pharmacology study and experimental validation. Active ingredients and relevant targets of JWPTL, as well as genes for endometriosis-related pain, were collected from public databases. Prediction of core targets and pathways of JWPTL against pain associated with endometriosis by protein-protein interaction (PPI) network work, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis. The Sprague-Dawley rat endo-metriosis model was constructed using the autologous endosomal transplantation method, and the successfully modeled rats were randomly divided into the model group and the JWPTL group, with 8 rats in each group. Another 8 rats were set up in the sham group. Rats in the JWPTL group used the rectal delivery method with the addition of JWPTL (7.77 g·kg-1·d-1) once a day for 28 d. Rats in the model and sham-operated groups were given equal amounts of saline using the same administration method. The 50% paw withdrawal threshold (PWT) of the rats was measured at different time points. After the intervention, the expression of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) proteins and mRNA in endometriotic tissues was detected by immune-ohistochemistry and reverse transcription-polymerase chain reaction. From GeneCards, Online Mendelian Inheritance in Man and other databases, a total of 964 endometriosis (EMs) -related pain targets were screened, 142 active ingredients of JWPTL, 605 targets, and 221 potential targets were obtained by intersection of Venn diagram; 44 core targets were identified by constructing PPI network. KEGG enrichment analysis showed that JWPTL mainly involves the PI3K-Akt signaling pathway, estrogen signaling pathway, hypoxia inducible factor-1 signaling pathway, tumour necrotizing factor signaling pathway, and other signaling pathways in the treatment of EMs-related pain. Animal experiments showed that JWPTL could up-regulate the mechanical pain threshold and reduce the expression of PI3K and Akt proteins and mRNA in ectopic endometrial tissues of model rats. The present study preliminarily analyzed the pharmacological mechanism of the formula, and molecular docking and animal experiments showed the feasibility of this study, suggesting that the formula may inhibit the release of inflammatory factors and reverse the pain associated with EMs by downregulating the PI3K/Akt signaling pathway.

A molecular docking insight: Phyllanthus niruri L. constituents targeting MMP-9 for angiogenesis inhibition and IL-1beta for antiinflammatory action in endometriosis therapy

Endometriosis, characterized by inflammatory lesions resembling endometrium outside the uterine cavity, induces chronic inflammation, anatomical changes and persistent pain. The expression of Interleukin 1beta (IL-1beta) is significantly associated with endometriosis, contributing to inflammatory process and fertility issues. Matrix metalloproteinase 9 (MMP-9) is crucial in the adhesion and angiogenesis of endometrial tissue. This study investigates the potential of Phyllanthus niruri L. in inhibiting MMP-9 and IL-1beta through molecular docking analysis. Molecular docking was performed using Discovery Studio Visualizer, Open Babel, PyRx and AutoDock Vina. The inhibitory activities of bioactive compounds on MMP-9 and IL-1beta were predicted. Biological activity and cytotoxicity were assessed using PASS and CLC-Pred respectively. Kaempferol and quercetin from P. niruri exhibited significant MMP-9 expression inhibitory activity. Search Tool for Interacting Chemicals (STITCH) analysis revealed interactions of quercetin and galangin with specific proteins involved in pathways related to endometriosis. Biological activity analysis indicated that quercetin, kaempferol, herbacetin and galangin show potential as MMP -9 expression inhibitors. CLC-Pred analysis suggested high cytotoxicity of kaempferol against glioma. Molecular docking results showed quercetin's potential as an MMP-9 inhibitor and galangin's potential as an IL-1 beta inhibitor. These findings support the therapeutic potential of P. niruri for endometriosis, providing insights for further research in developing innovative therapies targeting endometriosis-related inflammation and angiogenesis.