scholarly journals 5-Hydroxymethylcytosine Promotes Proliferation of Human Uterine Leiomyoma: A Biological Link to a New Epigenetic Modification in Benign Tumors

2014 ◽  
Vol 99 (11) ◽  
pp. E2437-E2445 ◽  
Author(s):  
Antonia Navarro ◽  
Ping Yin ◽  
Masanori Ono ◽  
Diana Monsivais ◽  
Molly B. Moravek ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Uterine Leiomyoma ◽  
Reproductive Tract ◽  
Enzyme Inhibitor ◽  
Malignant Tumors ◽  
Epigenetic Modification ◽  
Uterine Fibroids ◽  
Female Reproductive Tract ◽  
Immunofluorescent Staining ◽  
Benign Tumors

Context: Uterine leiomyoma, or fibroids, represent the most common benign tumors of the female reproductive tract. A newly discovered epigenetic modification, 5-hydroxymethylation (5-hmC), and its regulators, the TET (Ten Eleven Translocation) enzymes, were implicated in the pathology of malignant tumors; however, their roles in benign tumors, including uterine fibroids, remain unknown. Objective: To determine the role of 5-hmC and TET proteins in the pathogenesis of leiomyoma using human uterine leiomyoma and normal matched myometrial tissues and primary cells. Design: 5-hmC levels were determined by ELISA and immunofluorescent staining in matched myometrial and leiomyoma tissues. TET expression was analyzed by quantitative RT-PCR and immunoblotting. TET1 or TET3 were silenced or inhibited by small interfering RNA or 2-hydroxyglutarate to study their effects on 5-hmC content and cell proliferation. Results: We demonstrated significantly higher 5-hmC levels in the genomic DNA of leiomyoma tissue compared to normal myometrial tissue. The increase in 5-hmC levels was associated with the up-regulation of TET1 or TET3 mRNA and protein expression in leiomyoma tissue. TET1 or TET3 knockdown significantly reduced 5-hmC levels in leiomyoma cells and decreased cell proliferation. Treatment with 2-hydroxyglutarate, a competitive TET enzyme inhibitor, significantly decreased both 5-hmC content and cell proliferation of leiomyoma cells. Conclusion: An epigenetic imbalance in the 5-hmC content of leiomyoma tissue, caused by up-regulation of the TET1 and TET3 enzymes, might lead to discovery of new therapeutic targets in leiomyoma.

Mechanical Signaling and Extracellular Matrix in Uterine Fibroids

2017 ◽  
Vol 35 (06) ◽  
pp. 487-493 ◽  
Author(s):  
Saima Rafique ◽  
James Segars ◽  
Phyllis Leppert
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Reproductive Tract ◽  
Critical Role ◽  
Uterine Fibroids ◽  
Female Reproductive Tract ◽  
Benign Tumors ◽  
Mechanical Signaling ◽  
Abnormal Cells ◽  
Fibroid Growth

AbstractFibroids (uterine leiomyomas) are the most common benign tumors of the female reproductive tract. Steroid hormones, growth factors, and cytokines have long been implicated in fibroid growth; however, research suggests that changes in the extracellular matrix and mechanical signaling play a critical role in fibroid growth and differentiation. Studies have shown that growth of fibroids is related to the change in the volume and composition of extracellular matrix with increased deposition of abnormal collagen, glycoproteins, laminins, fibronectins, and an increased osmotic stress. These changes generate mechanical stress which is converted to chemical signals in the cells through mechanotransduction and eventually affects gene expression and protein synthesis. Current studies also suggest that mechanical signaling in fibroid cells is abnormal as evidenced by decreased apoptosis of abnormal cells and deposition of a stiff extracellular matrix promoting fibrosis. Understanding and defining these mechanisms could help design new therapies for the treatment of fibroids.

Simvastatin inhibits Wnt/β-catenin pathway in uterine leiomyoma

Endocrinology ◽  
2021 ◽  
Author(s):  
Malak El Sabeh ◽  
Subbroto Kumar Saha ◽  
Sadia Afrin ◽  
Mostafa A Borahay
Keyword(s):  
Uterine Leiomyoma ◽  
Reproductive Tract ◽  
Controlled Trial ◽  
Active Form ◽  
Cell Types ◽  
Female Reproductive Tract ◽  
Benign Tumors ◽  
Therapeutic Effects

Abstract The Wnt/β-catenin pathway is upregulated in uterine leiomyomas, the most common benign tumors in the female reproductive tract. Simvastatin is an anti-hyperlipidemic drug, and previous in vitro and in vivo reports showed it may have therapeutic effects in treating leiomyomas. The objective of this study is to examine the effects of simvastatin on the Wnt/β-catenin signaling pathway in leiomyoma. We treated primary and immortalized human leiomyoma cells with simvastatin and examined its effects using RT-qPCR, Western Blotting, and immunocytochemistry. We also examined the effects using human leiomyoma tissues from an ongoing, randomized controlled trial where women with symptomatic leiomyoma received simvastatin (40mg) or placebo for 3 months prior to their surgery. The results of this study reveal that simvastatin significantly reduced the expression of Wnt4 and its co-receptor LRP5. After simvastatin treatment, levels of total β-catenin and its active form, non-phosphorylated β-catenin, were reduced in both cell types. Additionally, simvastatin reduced the expression of Wnt4 and total β-catenin, as well as non-phosphorylated β-catenin protein expression in response to estrogen and progesterone. Simvastatin also inhibited the expression of c-Myc, a downstream target of the Wnt/β-catenin pathway. The effect of simvastatin on non-phosphorylated-β-catenin, the key regulator of the Wnt/β-catenin pathway, was recapitulated in human leiomyoma tissue. These results suggest that simvastatin may have a beneficial effect on uterine leiomyoma through suppressing the overactive Wnt/β-catenin pathway.

scholarly journals A study to correlate association between vitamin D with fibroid and its supplementation in the progression of the disease

2020 ◽  
Vol 9 (4) ◽  
pp. 1477
Author(s):  
Somila Xess ◽  
Jaiprakash Sahu
Keyword(s):  
Vitamin D ◽  
Reproductive Tract ◽  
Uterine Fibroids ◽  
Hypovitaminosis D ◽  
Vitamin D Supplementation ◽  
Female Reproductive Tract ◽  
Benign Tumors ◽  
Control Group ◽  
Study Group ◽  
Increased Risk

Background: Uterine fibroids, or leiomyomas are the most common benign tumors of the female reproductive tract, affecting up to 60% of Indian women with only 25% of women who are symptomatic. Symptoms do not always correlate with the size, number, or location of the fibroids. Recent studies suggest that hypovitaminosis D is associated with an increased risk of uterine fibroids.Methods: Total 110 women diagnosed with fibroid in USG were included in the study. Inclusion and exclusion criteria were applied and size of the fibroid noted. 60 women were included in the study group who took Vitamin D supplementation and 50 women in the control group who didn’t perform the study properly.Results: The growth pattern of fibroids with study group under supplementation with 25-OH-D3 seems to be stable, with no increases or decreases in size or number of identified lesions. Instead, women in control group, who did not perform appropriate vitamin D supplementation seem to have a slight but significant increase in size of the lesions.Conclusions: It was seen that hypovitaminosis D was associated with fibroid and thus supplementation with Vitamin D helped in the shrinkage of fibroid or slower the progression of the disease.

Determinants of Uterine Fibroids Among Married Women Attending Public Hospitals in Lahore, Pakistan

2020 ◽  
pp. 33-37
Author(s):  
OJS Admin
Keyword(s):  
Smooth Muscle ◽  
Reproductive Tract ◽  
Uterine Fibroids ◽  
Married Women ◽  
Female Reproductive Tract ◽  
Public Hospitals ◽  
Benign Tumors

Uterine broids (leiomyomas) are the most common tumors of female reproductive tract; these are the benign tumors of smooth muscle. Fibroids have been reported to occur in up to 70% of women by the age of 50 years.

Uterine Fibroids: Bridging Genomic Defects and Chronic Inflammation

2017 ◽  
Vol 35 (06) ◽  
pp. 494-498 ◽  
Author(s):  
Abdeljabar El Andaloussi ◽  
Zuni Chaudhry ◽  
Ayman Al-Hendy ◽  
Nahed Ismail
Keyword(s):  
Reproductive Tract ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Uterine Fibroids ◽  
The United States ◽  
Female Reproductive Tract ◽  
Driver Mutations ◽  
Benign Tumors ◽  
Med12 Gene ◽  
Abnormal Vaginal Bleeding

AbstractUterine fibroids (UF; aka leiomyoma, myomas) are the most common benign tumors of female reproductive tract. They are highly prevalent, with 70 to 80% of women burdened by the end of their reproductive years. Fibroids are a leading cause of pelvic pain, abnormal vaginal bleeding, pelvic bulk symptoms, miscarriage, and infertility. They are the leading indication for hysterectomy, and costs exceed 34 billion dollars annually in the United States alone. Recently, somatic mutations in exons 1 and 2 of Med12 gene emerged as common UF driver mutations. Unfortunately, the detailed etiology of UF is not fully realized. Particularly, very little is known about possible dysregulation of inflammatory and immune processes and their possible contribution to UF pathogenesis. The notion on possible impact of altered estrogen and progesterone signaling in UF on inflammatory responses and DNA repair machinery that can conceivably lead to tumor-specific somatic mutation is indeed an intriguing concept which has some foundation in available observation in other hormonally responsive tissues. This review highlights and summarizes our current knowledge on the convergence of such pathways and their relevance for UF pathogenesis.

scholarly journals Effects of miRNA-199a-5p on cell proliferation and apoptosis of uterine leiomyoma by targeting MED12

Open Medicine ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. 151-159
Author(s):  
Wei Zhao ◽  
Yingyan Zhao ◽  
Ling Chen ◽  
Yan Sun ◽  
Sumei Fan
Keyword(s):  
Cell Proliferation ◽  
Uterine Leiomyoma ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Reproductive Tract ◽  
Quantitative Polymerase Chain Reaction ◽  
Female Reproductive Tract ◽  
Cell Counting ◽  
Proliferation And Apoptosis

Abstract Background/aims Uterine leiomyoma (ULM) is a kind of gene-involved benign tumor, which is located in the front of female reproductive tract. It is one of the most common reproductive tract tumors in women, which leads to abnormal menstruation, repeated pregnancy loss, and other serious gynecological diseases. Recently, microRNAs (miRNAs) have attracted much more attention in the process of exploring the molecular mechanisms of tumorigenesis. Furthermore, the deregulated miRNAs had been reported to play important roles in ULM pathology. Methods In this study, we assessed the expression level of microRNA-199a-5p (miR-199a-5p) in human ULM by quantitative polymerase chain reaction. After that cell counting kit 8, colony formation, 5-ethynyl-20-deoxyuridine, flow cytometry, and Western blot analyses were performed to investigate the effects of miR-199a-5p on ULM cell proliferation and apoptosis. Results We confirmed that miR-199a-5p was significantly downregulated in human ULM. The results of function analyses showed that miR-199a-5p inhibited cell proliferation and induced cell apoptosis in vitro. Bioinformatics tool showed oncogene MED12 was one of the target genes of miR-199a-5p, which mediated the effect of miR-199a-5p on the ULM. Conclusion Our results showed that miR-199a-5p functioned as an antitumor factor in human ULM cells. These findings broaden the current findings on the function of miR-199a-5p into the ULM pathogenesis, and miR-199a-5p may serve as a prognosis and therapeutic target for the ULM and its related diseases.

The application of electron microscopy to diagnosis in gynecologic neoplasms and tumor-like conditions

1984 ◽  
Vol 42 ◽  
pp. 102-105
Author(s):  
Lawrence M. Roth
Keyword(s):  
Electron Microscopy ◽  
Reproductive Tract ◽  
Malignant Tumors ◽  
Frozen Section ◽  
Cost Effective ◽  
Female Reproductive Tract ◽  
Ultrastructural Examination ◽  
Specific Diagnosis ◽  
Potential Value ◽  
Gynecologic Neoplasms

The female reproductive tract may be the site of a wide variety of benign and malignant tumors, as well as non-neoplastic tumor-like conditions, most of which can be diagnosed by light microscopic examination including special stains and more recently immunoperoxidase techniques. Nevertheless there are situations where ultrastructural examination can contribute substantially to an accurate and specific diagnosis. It is my opinion that electron microscopy can be of greatest benefit and is most cost effective when applied in conjunction with other methodologies. Thus, I have developed an approach which has proved useful for me and may have benefit for others. In cases where it is deemed of potential value, glutaraldehyde-fixed material is obtained at the time of frozen section or otherwise at operation. Coordination with the gynecologic oncologist is required in the latter situation. This material is processed and blocked and is available if a future need arises.

scholarly journals The LH/hCG Axis in Endometrial Cancer: A New Target in the Treatment of Recurrent or Metastatic Disease

2010 ◽  
Vol 2010 ◽  
pp. 1-5 ◽  
Author(s):  
A. Arcangeli ◽  
I. Noci ◽  
A. Fortunato ◽  
G. F. Scarselli
Keyword(s):  
Cell Proliferation ◽  
Endometrial Cancer ◽  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
Proliferation And Apoptosis ◽  
Cell Invasiveness ◽  
Activate Protein Kinase ◽  
Kinase A

Endometrial cancer (EC) is a hormone-dependent cancer that currently represents the most frequent malignancy of the female reproductive tract. The involvement of steroid hormones in EC etiology and progression has been reported. More recently, gonadotropins, and, in particular LH/hCG, are emerging as novel regulators of tumor progression. In the present review, we discuss the role of the LH/hCG axis (i.e. LH/hCG and its receptors, LH/hCG-R) in both gonadal and nongonadal tissues, in physiological and neoplastic conditions. In cancer cells, LH/hCG mainly controls cell proliferation and apoptosis. In particular, in EC LH/hCG improves cell invasiveness, through a mechanism which involves the LH/hCG-R, which in turn activate protein kinase A and modulate integrin adhesion receptors. Indeed, the LH/hCG-R mRNA is expressed in primary ECs and this expression correlates with LH/hCG-induced cell invasiveness in vitro. These results lead to hypothesize that recurrent and metastatic ECs, which express LH/hCG-R, could benefit from therapies aimed at decreasing LH levels, through Gn-RH analogues. Hence, the LH/hCG axis could represent a prognostic factor and a new therapeutic target in EC.

Giant Uterine Fibroid in a Low Resources Setting: A Case Report

2020 ◽  
Vol 31 (2) ◽  
pp. 70-78
Author(s):  
Godwin S. Macheku ◽  
Lengarivo Losaru ◽  
Ibreck Msafiri ◽  
Harry Mwerinde ◽  
Anne E. Shuma ◽  
...  
Keyword(s):  
Uterine Fibroid ◽  
Uterine Leiomyoma ◽  
Imaging Modality ◽  
Uterine Leiomyomas ◽  
Female Reproductive Tract ◽  
Advanced Technology ◽  
Laboratory Evaluation ◽  
Benign Tumors ◽  
Abdominal Pressure ◽  
Supracervical Hysterectomy

Background: Uterine leiomyomas represent the most common benign tumors of the female reproductive tract. Giant uterine leiomyomas are exceedingly rare neoplasm and represents a great diagnostic and therapeutic challenge. The aim of this publication is that though the present era is of advanced technology and minimally invasive surgery but this may not be available everywhere and feasible in every case. Diagnosis and management of giant uterine myoma should permit greater management flexibility with safe options, which must be tailored to the individual clinical situation.Case presentation: A 45-year old woman presented with a 12-month history of progressive increasing abdominal size, prolonged menstrual bleeding, menorrhagia, gradual weight gain, vague abdominal pressure sensations, dysmenorrhea, abdominal and pelvic pain, frequent urination, relative constipation and symptom of anemia but not in failure. Physical examination, laboratory evaluation and a trans-abdominal ultrasound were done and findings suggested a giant abdominal-pelvic mass. Abdominal supracervical hysterectomy with bilateral salpingo-oophorectomy was performed. Histologically, the specimen was 16.2 Kg uterine leiomyoma measuring 30/24/20 cm, intramural and subserosal myomatous, cellular leiomyoma that occurred without secondary changes, necrosis, cellular atypia, or mitosis.The patient’s postoperative progress was uneventful and she was discharged from the hospital on the seventh postoperative day.Conclusion: In uterine leiomyomas patient, the preferred imaging modality for initial evaluation is ultrasonography because it is the least invasive and most cost effective investigation especially in low resource settings where magnetic resonance imaging (MRI) and computed tomography (CT) Scan are usually not available and majority of the patients cannot afford its cost. The chosen treatment should be individualized, both severity of symptoms and patients desire to preserve fertility are very important. There is no single best approach to uterine fibroid treatment. However, women with giant uterine fibroids are best treated surgically and require adequate pre-operative preparations and an experienced skillful surgeon. Keywords: Giant uterine leiomyoma, diagnosis, supracervical hysterectomy.

scholarly journals Kisspeptin modulates fertilization capacity of mouse spermatozoa

Reproduction ◽  
2014 ◽  
Vol 147 (6) ◽  
pp. 835-845 ◽  
Author(s):  
Meng-Chieh Hsu ◽  
Jyun-Yuan Wang ◽  
Yue-Jia Lee ◽  
De-Shien Jong ◽  
Kuan-Hao Tsui ◽  
...  
Keyword(s):  
Reproductive Tract ◽  
Expression Profiles ◽  
Female Reproductive Tract ◽  
Response To Treatment ◽  
Immunofluorescent Staining ◽  
Seminiferous Tubules ◽  
Reproductive Tissues ◽  
Male Gametes ◽  
Regulatory Systems ◽  
Fertilization Capacity

Kisspeptin acts as an upstream regulator of the hypothalamus–pituitary–gonad axis, which is one of the main regulatory systems for mammalian reproduction.Kiss1and its receptorKiss1r(also known as G protein-coupled receptor 54 (Gpr54)) are expressed in various organs, but their functions are not well understood. The purpose of this study was to investigate the expression profiles and functions of kisspeptin and KISS1R in the reproductive tissues of imprinting control region mice. To identify the expression pattern and location of kisspeptin and KISS1R in gonads, testes and ovarian tissues were examined by immunohistochemical or immunofluorescent staining. Kisspeptin and KISS1R were expressed primarily in Leydig cells and seminiferous tubules respectively. KISS1R was specifically localized in the acrosomal region of spermatids and mature spermatozoa. Kisspeptin, but not KISS1R, was expressed in the cumulus–oocyte complex and oviductal epithelium of ovarian and oviductal tissues. The sperm intracellular calcium concentrations significantly increased in response to treatment with kisspeptin 10 in Fluo-4-loaded sperm. The IVF rates decreased after treatment of sperm with the kisspeptin antagonist peptide 234. These results suggest that kisspeptin and KISS1R might be involved in the fertilization process in the female reproductive tract. In summary, this study indicates that kisspeptin and KISS1R are expressed in female and male gametes, respectively, and in mouse reproductive tissues. These data strongly suggest that the kisspeptin system could regulate mammalian fertilization and reproduction.

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