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Reproductive Sciences (Thousand Oaks,... Mar 2016Uterine leiomyoma are a common benign pelvic tumors composed of modified smooth muscle cells and a large amount of extracellular matrix (ECM). The proteoglycan...
Uterine leiomyoma are a common benign pelvic tumors composed of modified smooth muscle cells and a large amount of extracellular matrix (ECM). The proteoglycan composition of the leiomyoma ECM is thought to affect pathophysiology of the disease. To test this hypothesis, we examined the abundance (by immunoblotting) and expression (by quantitative real-time polymerase chain reaction) of the proteoglycans biglycan, decorin, and versican in leiomyoma and normal myometrium and determined whether expression is affected by steroid hormones and menstrual phase. Leiomyoma and normal myometrium were collected from women (n = 17) undergoing hysterectomy or myomectomy. In vitro studies were performed on immortalized leiomyoma (UtLM) and normal myometrial (hTERT-HM) cells with and without exposure to estradiol and progesterone. In leiomyoma tissue, abundance of decorin messenger RNA (mRNA) and protein were 2.6-fold and 1.4-fold lower, respectively, compared with normal myometrium. Abundance of versican mRNA was not different between matched samples, whereas versican protein was increased 1.8-fold in leiomyoma compared with myometrium. Decorin mRNA was 2.4-fold lower in secretory phase leiomyoma compared with proliferative phase tissue. In UtLM cells, progesterone decreased the abundance of decorin mRNA by 1.3-fold. Lower decorin expression in leiomyoma compared with myometrium may contribute to disease growth and progression. As decorin inhibits the activity of specific growth factors, its reduced level in the leiomyoma cell microenvironment may promote cell proliferation and ECM deposition. Our data suggest that decorin expression in leiomyoma is inhibited by progesterone, which may be a mechanism by which the ovarian steroids affect leiomyoma growth and disease progression.
Topics: Adult; Cell Line, Transformed; Cell Line, Tumor; Decorin; Estradiol; Female; Humans; Leiomyoma; Middle Aged; Myometrium; Progesterone; Promegestone; Proteoglycans; Uterine Neoplasms
PubMed: 26423601
DOI: 10.1177/1933719115607994 -
Annals of Biomedical Engineering Jul 2017Research insights into uterine function and the mechanisms of labour have been hindered by the lack of suitable animal and cellular models. The use of traditional... (Review)
Review
Research insights into uterine function and the mechanisms of labour have been hindered by the lack of suitable animal and cellular models. The use of traditional culturing methods limits the exploration of complex uterine functions, such as cell interactions, connectivity and contractile behaviour, as it fails to mimic the three-dimensional (3D) nature of uterine cell interactions in vivo. Animal models are an option, however, use of these models is constrained by ethical considerations as well as translational limitations to humans. Evidence indicates that these limitations can be overcome by using 3D culture systems, or 3D Bioprinters, to model the in vivo cytological architecture of the tissue in an in vitro environment. 3D cultured or 3D printed cells can be used to form an artificial tissue. This artificial tissue can not only be used as an appropriate model in which to study cellular function and organisation, but could also be used for regenerative medicine purposes including organ or tissue transplantation, organ donation and obstetric care. The current review describes recent developments in cell culture that can facilitate the development of myometrial 3D structures and tissue engineering applications.
Topics: Animals; Bioprinting; Cell Culture Techniques; Female; Humans; Myometrium; Printing, Three-Dimensional; Tissue Engineering
PubMed: 27770218
DOI: 10.1007/s10439-016-1749-5 -
FASEB Journal : Official Publication of... Dec 2019Adiponectin is secreted by adipose tissue and promotes insulin sensitivity. Low circulating adiponectin is associated with increased risk for preterm labor, but the...
Adiponectin is secreted by adipose tissue and promotes insulin sensitivity. Low circulating adiponectin is associated with increased risk for preterm labor, but the influence of adiponectin on uterine myometrial physiology is unknown. We hypothesized that adiponectin receptors (AdipoRs) decrease myometrial contractility AMPK to promote uterine quiescence in pregnancy. Using quantitative RT-PCR, we found that nonpregnant or pregnant human and mouse myometrium express AdipoR1 and AdipoR2 mRNAs. We confirmed AdipoR2 protein expression in human and mouse myometrium, with increased abundance in late mouse pregnancy. Both recombinant adiponectin and a pharmacologic AdipoR agonist, AdipoRon, potently inhibited uterine myometrial strip contractions in physiologic organ bath. The relaxation was independent of contractile stimulus (oxytocin, KCl, U46619). AdipoR agonists increased AMPK phosphorylation in pregnant mouse myometrium, and the direct AMPK activator A769662 also relaxed myometrial strips. However, the AMPK inhibitor dorsomorphin (compound C) blocked AMPK phosphorylation but did not abolish relaxation with either AdipoRon or A769662. In summary, adiponectin inhibits myometrial contractility consistent with the possibility that it is a previously unrecognized link between maternal metabolism and pregnancy maintenance. We also identify a separate role for AMPK regulating myometrial contractions that may influence labor onset.-Vyas, V., Guerra, D. D., Bok, R., Powell, T., Jansson, T., Hurt, K. J. Adiponectin links maternal metabolism to uterine contractility.
Topics: AMP-Activated Protein Kinase Kinases; Adiponectin; Adult; Animals; Female; Humans; Mice; Mice, Inbred C57BL; Middle Aged; Muscle Contraction; Myometrium; Pregnancy; Protein Kinases; Receptors, Adiponectin
PubMed: 31665924
DOI: 10.1096/fj.201901646R -
PloS One 2020Preterm birth is recognized as the primary cause of infant mortality worldwide. Twin pregnancies are significantly more at risk of preterm birth than singleton...
Preterm birth is recognized as the primary cause of infant mortality worldwide. Twin pregnancies are significantly more at risk of preterm birth than singleton pregnancies. A greater understanding of why this is and better modes of treatment and prevention are needed. Key to this is determining the differing pathophysiological mechanisms of preterm birth in twins, including the role of the myometrium and premature uterine contraction. We performed RNA sequencing (RNA-Seq) of human myometrium from singleton and twin pregnancies at term (> 37+0 weeks) and preterm (< 37+0 weeks), collected during pre-labour Caesarean Section. RNA-Seq libraries were prepared from polyA-selected RNA and sequenced on the Illumina HiSeq 4000 platform. Differentially expressed genes (DEGs), GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment were conducted using R software. Significance was determined with a false discovery rate-adjusted P value of <0.05. Only 3 DEGs were identified between gestational age-matched singleton and twin myometrium and only 1 DEG identified between singleton term and twin preterm tissues. Comparison of singleton preterm myometrium with twin term myometrium however, revealed 75 down-regulated and 24 up-regulated genes in twin myometrium. This included genes associated with inflammation and immune response, T cell maturation and differentiation and steroid biosynthesis. GO and KEGG enrichment analyses for biologically relevant processes and functions also revealed several terms related to inflammation and immune response, as well as cytokine-cytokine receptor interaction and chemokine receptor signalling. Data indicate that little or no differences exist in the transcriptome of singleton and twin myometrium when matched for gestational age. The significant up- and down-regulation of genes identified between preterm singleton and twin myometrium at term may point to transcriptome changes associated with the chronic levels of uterine stretch in twin pregnancy or genes associated with the myometrium transitioning to labour onset.
Topics: Adult; Cesarean Section; Female; Gene Expression Regulation; Humans; Immunity, Innate; Infant; Infant, Newborn; Inflammation; Myometrium; Pregnancy; Pregnancy, Twin; Premature Birth; Sequence Analysis, RNA; Transcriptome
PubMed: 31951633
DOI: 10.1371/journal.pone.0227882 -
International Journal of Gynecological... Nov 2021Vascular pseudoinvasion or displacement of tumor or normal endometrial tissue is a potential pitfall in uterine pathology. The proposed mechanisms of this phenomenon are...
Vascular pseudoinvasion or displacement of tumor or normal endometrial tissue is a potential pitfall in uterine pathology. The proposed mechanisms of this phenomenon are mostly associated with the uterine manipulator used during minimally invasive hysterectomies. The aim of this report is to describe vascular pseudoinvasion in a still unreported setting, that of a postendometrial ablation hysterectomy, and to provide a summary of studies dealing with artifactual or nonmalignant myometrial vessel involvement by normal or neoplastic endometrial tissue.
Topics: Endometrial Ablation Techniques; Endometrium; Female; Humans; Hysterectomy; Myometrium; Uterus
PubMed: 33323863
DOI: 10.1097/PGP.0000000000000748 -
Reproductive Sciences (Thousand Oaks,... Feb 2024Adenomyosis is associated with pelvic pain, abnormal uterine bleeding, and infertility. Several ultrasound-based classifications have been reported, but it is not clear... (Review)
Review
Adenomyosis is associated with pelvic pain, abnormal uterine bleeding, and infertility. Several ultrasound-based classifications have been reported, but it is not clear which criteria reflect the severity of symptoms. The aim of this review is to summarize the ultrasound features that correlate with clinical manifestations of adenomyosis and to discuss diagnostic methods for predicting disease severity. A literature search of PubMed and Google Scholar published up to March 2022 was performed. A consensus-based classification was determined primarily by defining the mapping or topography of the lesion. Ultrasound features can be classified into direct (i.e., the presence of ectopic endometrial tissue within the myometrium) and indirect findings (i.e., changes in the myometrial structure and translesional vascularity secondary to myometrial invasion). There are some reports that symptoms are positively correlated with the location and spread of the disease. Indeed, the lesion thickness, diffuse or internal adenomyosis, and focal adenomyosis may be associated with increased risks of dysmenorrhea, abnormal uterine bleeding, and infertility, respectively. Two ultrasound markers (i.e., the presence of heterogeneous myometrium and myometrial cysts) appear to be the criteria most clinicians focus on. However, decision-making on treatment necessity is determined by symptom severity rather than the topography of the lesions. There is currently no consensus that symptom severity can be predicted based on ultrasound features, but the ultrasound-based criteria may be helpful in diagnosing adenomyosis.
Topics: Female; Humans; Adenomyosis; Uterine Diseases; Ultrasonography; Myometrium; Infertility; Uterine Hemorrhage
PubMed: 37584856
DOI: 10.1007/s43032-023-01318-5 -
BioMed Research International 2017Adenomyosis or endometriosis genitalis interna is a frequent benign disease of women in fertile age. It causes symptoms like bleeding disorders and dysmenorrhea and... (Review)
Review
Adenomyosis or endometriosis genitalis interna is a frequent benign disease of women in fertile age. It causes symptoms like bleeding disorders and dysmenorrhea and seems to have a negative effect on fertility. Adenomyosis can be part of a complex genital and extragenital endometriosis but also can be found as a solitary uterine disease. While peritoneal endometriosis can be easily diagnosed by laparoscopy with subsequent biopsy, the determination of adenomyosis is difficult. In the following literature review, the diagnostic methods clinical history and symptoms, gynecological examination, 2D and 3D transvaginal ultrasound, MRI, hysteroscopy, and laparoscopy will be discussed step by step in order to evaluate their predictive value in the diagnosis of adenomyosis.
Topics: Adenomyosis; Adult; Endometrium; Female; Humans; Magnetic Resonance Imaging; Myometrium; Ultrasonography; Young Adult
PubMed: 29349064
DOI: 10.1155/2017/1514029 -
Reproductive Sciences (Thousand Oaks,... Mar 2021The bioelectrical signals that produce uterine contractions during parturition are not completely understood. The objectives are as follows: (1) to review the literature... (Comparative Study)
Comparative Study Review
Review and Study of Uterine Bioelectrical Waveforms and Vector Analysis to Identify Electrical and Mechanosensitive Transduction Control Mechanisms During Labor in Pregnant Patients.
The bioelectrical signals that produce uterine contractions during parturition are not completely understood. The objectives are as follows: (1) to review the literature and information concerning uterine biopotential waveforms generated by the uterus, known to produce contractions, and evaluate mechanotransduction in pregnant patients using electromyographic (EMG) recording methods and (2) to study a new approach, uterine vector analysis, commonly used for the heart: vectorcardiography analysis. The patients used in this study were as follows: (1) patients at term not in labor (n = 3); (2) patients during the 1st stage of labor at cervical dilations from 2 to 10 cm (n = 30); and (3) patients in the 2nd stage of labor and during delivery (n = 3). We used DC-coupled electrodes and PowerLab hardware (model no. PL2604, ADInstruments, Castle Hill, Australia), with software (LabChart, ADInstruments) for storage and analysis of biopotentials. Uterine and abdominal EMG recordings were made from the surface of each patient using 3 electrode pairs with 1 pair (+ and -, with a 31-cm spacing distance) placed in the right/left position (X position) and with 1 pair placed in an up/down position (Y position, also 31 cm apart) and with the third pair at the front/back (Z position). Using signals from the three X, Y, and Z electrodes, slow (0.03 to 0.1 Hz, high amplitude) and fast wave (0.3 to 1 Hz, low amplitude) biopotentials were recorded. The amplitudes of the slow waves and fast waves were significantly higher during the 2nd stage of labor compared to the 1st stage (respectively, p = 9.54 × e and p = 3.94 × e). When 2 channels were used, for example, the X vs. Y, for 2-D vector analysis or 3 channels, X vs. Y vs. Z, for 3-D analysis, are plotted against each other on their axes, this produces a vector electromyometriogram (EMMG) that shows no directionality for fast waves and a downward direction for slow waves. Similarly, during the 2nd stage of labor during abdominal contractions ("pushing"), the slow and fast waves were enlarged. Manual applied pressure was used to evoke bioelectrical activity to examine the mechanosensitivity of the uterus. Conclusions: (1) Phasic contractility of the uterus is a product of slow waves and groups of fast waves (bursts of spikes) to produce myometrial contractile responses. (2) 2-D and 3-D uterine vector analyses (uterine vector electromyometriogram) demonstrate no directionality of small fast waves while the larger slow waves represent the downward direction of biopotentials towards the cervical opening. (3) Myometrial cell action event excitability and subsequent contractility likely amplify slow wave activity input and uterine muscle contractility via mechanotransduction systems. (4) Models illustrate the possible relationships of slow to fast waves and the association of a mechanotransduction system and pacemaker activity as observed for slow waves and pacemakers in gastrointestinal muscle. (5) The interaction of these systems is thought to regulate uterine contractility. (6) This study suggests a potential indicator of delivery time. Such vector approaches might help us predict the progress of gestation and better estimate the timing of delivery, gestational pathologies reflected in bioelectric events, and perhaps the potential for premature delivery drug and mechanical interventions.
Topics: Animals; Biological Clocks; Electromyography; Female; Humans; Labor, Obstetric; Mechanotransduction, Cellular; Membrane Potentials; Models, Biological; Myometrium; Parturition; Periodicity; Pregnancy; Time Factors; Uterine Contraction
PubMed: 33090378
DOI: 10.1007/s43032-020-00358-5 -
The Journal of Physiology May 2023Approximately 10% of US births deliver preterm before 37 weeks of completed gestation. Premature infants are at risk for life-long debilitating morbidities and death,...
Approximately 10% of US births deliver preterm before 37 weeks of completed gestation. Premature infants are at risk for life-long debilitating morbidities and death, and spontaneous preterm labour explains 50% of preterm births. In all cases existing treatments are ineffective, and none are FDA approved. The mechanisms that initiate preterm labour are not well understood but may result from dysfunctional regulation of quiescence mechanisms. Human pregnancy is accompanied by large increases in blood flow, and the uterus must enlarge by orders of magnitude to accommodate the growing fetus. This mechanical strain suggests that stretch-activated channels may constitute a mechanism to explain gestational quiescence. Here we identify for the first time that Piezo1, a mechanosensitive cation channel, is present in the uterine smooth muscle and microvascular endothelium of pregnant myometrium. Piezo is downregulated during preterm labour, and stimulation of myometrial Piezo1 in an organ bath with the agonist Yoda1 relaxes the tissue in a dose-dependent fashion. Further, stimulation of Piezo1 while inhibiting protein kinase A, AKT, or endothelial nitric oxide synthase mutes the negative inotropic effects of Piezo1 activation, intimating that actions on the myocyte and endothelial nitric oxide signalling contribute to Piezo1-mediated contractile dynamics. Taken together, these data highlight the importance of stretch-activated channels in pregnancy maintenance and parturition, and identify Piezo1 as a tocolytic target of interest. KEY POINTS: Spontaneous preterm labour is a serious obstetric dilemma without a known cause or effective treatments. Piezo1 is a stretch-activated channel important to muscle contractile dynamics. Piezo1 is present in the myometrium and is dysregulated in women who experience preterm labour. Activation of Piezo1 by the agonist Yoda1 relaxes the myometrium in a dose-dependent fashion, indicating that Piezo1 modulation may have therapeutic benefits to treat preterm labour.
Topics: Pregnancy; Infant, Newborn; Humans; Female; Myometrium; Obstetric Labor, Premature; Uterus; Muscle, Smooth; Premature Birth; Ion Channels
PubMed: 35941750
DOI: 10.1113/JP283299 -
Human Reproduction Update Nov 2018Stem cell research in the endometrium and myometrium from animal models and humans has led to the identification of endometrial/myometrial stem cells and their niches....
BACKGROUND
Stem cell research in the endometrium and myometrium from animal models and humans has led to the identification of endometrial/myometrial stem cells and their niches. This basic knowledge is beginning to be translated to clinical use for incurable uterine pathologies. Additionally, the implication of bone marrow-derived stem cells (BMDSCs) in uterine physiology has opened the field for the exploration of an exogenous and autologous source of stem cells.
OBJECTIVE AND RATIONALE
In this review, we outline the progress of endometrial and myometrial stem/progenitor cells in both human and mouse models from their characterization to their clinical application, indicating roles in Asherman syndrome, atrophic endometrium and tissue engineering, among others.
SEARCH METHODS
A comprehensive search of PubMed and Google Scholar up to December 2017 was conducted to identify peer-reviewed literature related to the contribution of bone marrow, endometrial and myometrial stem cells to potential physiological regeneration as well as their implications in pathologies of the human uterus.
OUTCOMES
The discovery and main characteristics of stem cells in the murine and human endometrium and myometrium are presented together with the relevance of their niches and cross-regulation. The current state of advanced stem cell therapy using BMDSCs in the treatment of Asherman syndrome and atrophic endometrium is analyzed. In the myometrium, the understanding of genetic and epigenetic defects that result in the development of tumor-initiating cells in the myometrial stem niche and thus contribute to the growth of uterine leiomyoma is also presented. Finally, recent advances in tissue engineering based on the creation of novel three-dimensional scaffolds or decellularisation open up new perspectives for the field of uterine transplantation.
WIDER IMPLICATIONS
More than a decade after their discovery, the knowledge of uterine stem cells and their niches is crystalising into novel therapeutic approaches aiming to treat with cells those conditions that cannot be cured with drugs, particularly the currently incurable uterine pathologies. Additional work and improvements are needed, but the basis has been formed for this therapeutic application of uterine cells.
Topics: Animals; Endometrium; Female; Humans; Leiomyoma; Mice; Models, Animal; Myometrium; Stem Cell Transplantation; Stem Cells; Translational Research, Biomedical; Uterine Diseases
PubMed: 30239705
DOI: 10.1093/humupd/dmy028