-
Seminars in Reproductive Medicine Sep 2015Normal adult tissues contain a small subset of tissue-specific stem cells. These stem cells are capable of self-renewing as well as generating daughter cells that are... (Review)
Review
Normal adult tissues contain a small subset of tissue-specific stem cells. These stem cells are capable of self-renewing as well as generating daughter cells that are destined to completely differentiate and thereby support tissue remodeling and repair. The human uterus is an example of how such cell populations support the function of an organ. The uterus primarily consists of endometrium and myometrium, and these tissues rapidly enlarge to support the developing fetus during pregnancy. Uterine enlargement and remodeling can occur more than a dozen times during a woman's reproductive life. The expansion of the gravid uterus is achieved mainly through myometrial hyperplasia and hypertrophy, and these processes suggest an important role for stem/progenitor cell systems. Recently, stem/progenitor cells in the myometrium have been identified and their properties characterized. Here, we discuss some of the properties of myometrial stem/progenitor cells. We also suggest a new model of myometrial physiology and how stem cell systems might contribute to pregnancy-associated uterine remodeling.
Topics: Antigens, CD34; Female; Humans; Integrin alpha6; Myometrium; Pregnancy; Stem Cells
PubMed: 26308614
DOI: 10.1055/s-0035-1563602 -
Seminars in Reproductive Medicine May 2020Adenomyosis remains an enigmatic disease in the clinical and research communities. The high prevalence, diversity of morphological and symptomatic presentations, array... (Review)
Review
Adenomyosis remains an enigmatic disease in the clinical and research communities. The high prevalence, diversity of morphological and symptomatic presentations, array of potential etiological explanations, and variable response to existing interventions suggest that different subgroups of patients with distinguishable mechanistic drivers of disease may exist. These factors, combined with the weak links to genetic predisposition, make the entire spectrum of the human condition challenging to model in animals. Here, after an overview of current approaches, a vision for applying physiomimetic modeling to adenomyosis is presented. Physiomimetics combines a system's biology analysis of patient populations to generate hypotheses about mechanistic bases for stratification with in vitro patient avatars to test these hypotheses. A substantial foundation for three-dimensional (3D) tissue engineering of adenomyosis lesions exists in several disparate areas: epithelial organoid technology; synthetic biomaterials matrices for epithelial-stromal coculture; smooth muscle 3D tissue engineering; and microvascular tissue engineering. These approaches can potentially be combined with microfluidic platform technologies to model the lesion microenvironment and can potentially be coupled to other microorgan systems to examine systemic effects. In vitro patient-derived models are constructed to answer specific questions leading to target identification and validation in a manner that informs preclinical research and ultimately clinical trial design.
Topics: Adenomyosis; Endometrium; Female; Humans; Models, Biological; Myometrium; Tissue Engineering
PubMed: 33176387
DOI: 10.1055/s-0040-1719084 -
International Journal of Environmental... Nov 2021Classically, the diagnosis of adenomyosis relied on histological examination of uteri following hysterectomy and classifications focused on the depth of endometrial... (Review)
Review
Classically, the diagnosis of adenomyosis relied on histological examination of uteri following hysterectomy and classifications focused on the depth of endometrial invasion within the myometrium. There remain uncertainties around the cut-off point for the histological diagnosis. Imaging-based diagnosis enables recognition of the condition in women not undergoing surgery and facilitates the assessment of the extent of adenomyosis within the whole uterus, as well as of affections of the uterovesical pouch and of the pouch of Douglas. In this article, we explore the diagnostic uncertainties, the need to produce a classification of the condition and the challenges towards that goal. A distinction should be drawn between disease mapping and a classification that may link histological or image-based features with clinical characteristics, or with pathophysiology. An agreed system for reporting adenomyotic lesions may enable comparisons of research studies and thus contribute towards an informed classification. To this aim, we outline the features of the condition and explore the characteristics that are considered when producing a taxonomy. These include the latest proposal for subdivision of adenomyosis into an internal and an external variant. We also explore the uncertainties linked to classifying involvement of the uterovesical pouch, the pouch of Douglas and lesions in the outer myometrium. The limitations of currently available evidence suggest that agreement on a hypothesis to underpin a classification is unlikely at present. Therefore, current efforts will probably remain focused on disease mapping.
Topics: Adenomyosis; Endometriosis; Endometrium; Female; Humans; Hysterectomy; Myometrium; Uterus
PubMed: 34886111
DOI: 10.3390/ijerph182312386 -
Advances in Experimental Medicine and... 2019We start by describing the functions of the uterus, its structure, both gross and fine, innervation and blood supply. It is interesting to note the diversity of the... (Review)
Review
We start by describing the functions of the uterus, its structure, both gross and fine, innervation and blood supply. It is interesting to note the diversity of the female's reproductive tract between species and to remember it when working with different animal models. Myocytes are the overwhelming cell type of the uterus (>95%) and our focus. Their function is to contract, and they have an intrinsic pacemaker and rhythmicity, which is modified by hormones, stretch, paracrine factors and the extracellular environment. We discuss evidence or not for pacemaker cells in the uterus. We also describe the sarcoplasmic reticulum (SR) in some detail, as it is relevant to calcium signalling and excitability. Ion channels, including store-operated ones, their contributions to excitability and action potentials, are covered. The main pathway to excitation is from depolarisation opening voltage-gated Ca channels. Much of what happens downstream of excitability is common to other smooth muscles, with force depending upon the balance of myosin light kinase and phosphatase. Mechanisms of maintaining Ca balance within the myocytes are discussed. Metabolism, and how it is intertwined with activity, blood flow and pH, is covered. Growth of the myometrium and changes in contractile proteins with pregnancy and parturition are also detailed. We finish with a description of uterine activity and why it is important, covering progression to labour as well as preterm and dysfunctional labours. We conclude by highlighting progress made and where further efforts are required.
Topics: Animals; Calcium; Calcium Channels; Calcium Signaling; Female; Myometrium; Pregnancy; Sarcoplasmic Reticulum; Uterine Contraction; Uterus
PubMed: 31183830
DOI: 10.1007/978-981-13-5895-1_10 -
Journal of Ultrasound in Medicine :... Jun 2020
Topics: Female; Myometrium; Ultrasonography; Uterus
PubMed: 31916262
DOI: 10.1002/jum.15211 -
Ultrasound in Obstetrics & Gynecology :... Jul 2023The uterine junctional zone is the subendometrial area in the myometrium that contributes to peristalsis and aids in spermatozoa and blastocyst transport. Alterations in... (Review)
Review
The uterine junctional zone is the subendometrial area in the myometrium that contributes to peristalsis and aids in spermatozoa and blastocyst transport. Alterations in the appearance of the junctional zone on transvaginal sonography (TVS) or magnetic resonance imaging (MRI) are associated with adenomyosis. The lack of standardization of description of its appearance and ill-defined boundaries on both histology and imaging hamper understanding of the junctional zone and limit its role in the diagnosis of adenomyosis. The objectives of this review were to investigate the accordance in definition of the junctional zone across different diagnostic approaches and to examine how imaging findings can be linked to histological findings in the context of diagnosis of adenomyosis. A comprehensive literature review was conducted of articles describing the appearance on imaging and the histological structure of the uterine junctional zone. Our review suggests that the junctional zone is distinguished from the middle and outer myometrium by gradual changes in smooth-muscle cell density, extracellular space, connective tissue, water content and vascular properties. However, while the signal intensity from the junctional zone to the middle myometrium changes abruptly on MRI, the histopathological changes are gradual and its border may be difficult or impossible to distinguish on two-dimensional TVS. Moreover, the thickness of the junctional zone measured on MRI is larger than that measured on TVS. Thus, these two imaging modalities reflect this zone differently. Although a thickened junctional zone is often used to diagnose adenomyosis on MRI, the presence of adenomyosis can be described more accurately as interruptions of the junctional zone by endometrial tissue, which leads to direct signs on imaging such as subendometrial lines and buds on two- and three-dimensional TVS or bright foci on MRI. The histopathological criteria for diagnosis are based on enlargement of the uterus with severe adenomyosis, and might not reflect its early stages. Clinicians should be aware that findings on MRI cannot be extrapolated readily to ultrasound. An understanding of this is necessary when investigating the uterine junctional zone as a functional unit and the association between visualization of direct features of adenomyosis in the junctional zone and clinical symptoms. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Pregnancy; Female; Humans; Adenomyosis; Uterus; Myometrium; Ultrasonography; Magnetic Resonance Imaging; Endometriosis
PubMed: 36370446
DOI: 10.1002/uog.26117 -
International Journal of Environmental... May 2022Uterine adenomyosis is a common benign condition defined by the presence of heterotopic endometrial glands and stroma within the myometrium. Adenomyosis is often related... (Review)
Review
Uterine adenomyosis is a common benign condition defined by the presence of heterotopic endometrial glands and stroma within the myometrium. Adenomyosis is often related to infertility and other adverse pregnancy outcomes. Modern imaging techniques allow the non-invasive diagnosis of adenomyosis and, in this framework, Magnetic Resonance Imaging (MRI) has assumed a central role due to its high diagnostic accuracy in the detection of adenomyosis. Currently, there is still a lack of international consensus on adenomyosis diagnostic criteria and classification, despite the fact that an agreed reporting system would promote treatment outcomes and research. This review aims to emphasize the important contribution of MRI to the diagnosis of adenomyosis and to highlight how, thanks to the great tissue differentiation provided by MRI, it is possible to identify the main direct (cystic component) and indirect (junctional zone features) signs of adenomyosis and to distinguish its various subtypes according to different MRI-based classifications. We also explored the main MRI criteria to identify the most common pitfalls and differential diagnoses of adenomyosis, whose features should be considered to avoid misdiagnosis.
Topics: Adenomyosis; Endometrium; Female; Humans; Magnetic Resonance Imaging; Myometrium; Pregnancy; Radiologists
PubMed: 35627376
DOI: 10.3390/ijerph19105840 -
Reproduction (Cambridge, England) Jan 2021Intermittent myometrial hypoxia is a normal feature of labour, as the powerful contractions compress blood vessels. In this review, we focus on the relation between... (Review)
Review
Intermittent myometrial hypoxia is a normal feature of labour, as the powerful contractions compress blood vessels. In this review, we focus on the relation between hypoxia, myometrial metabolism, and contractility. We dissect how hypoxia can feedback and limit an ongoing contraction and help prevent foetal distress. The mechanisms involve acidification from lactate, decreased excitability, and a fall of intracellular calcium concentration. As this cycle of contraction and relaxation repeats in labour, the hypoxia also engenders mechanisms that increase force; hypoxia-induced force increase, HIFI. We also discuss the role of the myometrial blood vessels in dysfunctional labour, which is associated with lactic acidosis. In synthesising these studies, we have attempted to unify findings by considering the importance of experimental protocols and finding direct mechanistic evidence from human myometrium or in vivo studies. We have made suggestions for future studies to fill the holes in our understanding and speed up the translation of our knowledge to improve births for mothers and babies everywhere.
Topics: Dystocia; Female; Humans; Hypoxia; Labor, Obstetric; Myometrium; Pregnancy; Reproductive Health; Uterine Contraction; Uterus
PubMed: 33112773
DOI: 10.1530/REP-20-0327 -
Trends in Endocrinology and Metabolism:... Jul 2018Progesterone acts through the progesterone receptor to direct physiological adaption of the uterus in preparation and completion of pregnancy. Genome-wide transcriptome... (Review)
Review
Progesterone acts through the progesterone receptor to direct physiological adaption of the uterus in preparation and completion of pregnancy. Genome-wide transcriptome and cistrome analyses have uncovered new members and novel modifiers of the progesterone signaling pathway. Genetically engineered mice allow functional assessment of newly identified genes in vivo and provide insights on the impact of progesterone receptor-dependent molecular mechanisms on pregnancy at the organ system level. Progesterone receptor isoforms collectively mediate progesterone signaling via their distinct and common downstream target genes, which makes the stoichiometry of isoforms relevant in modifying the progesterone activity. This review discusses recent advances on the discovery of the progesterone receptor network, with special focus on the endometrium at early pregnancy and myometrium during parturition.
Topics: Animals; Female; Humans; Myometrium; Parturition; Pregnancy; Receptors, Progesterone; Signal Transduction
PubMed: 29705365
DOI: 10.1016/j.tem.2018.04.001 -
Annual Review of Physiology Feb 2021We address advances in the understanding of myometrial physiology, focusing on excitation and the effects of gestation on ion channels and their relevance to labor. This... (Review)
Review
We address advances in the understanding of myometrial physiology, focusing on excitation and the effects of gestation on ion channels and their relevance to labor. This review moves through pioneering studies to exciting new findings. We begin with the myometrium and its myocytes and describe how excitation might initiate and spread in this myogenic smooth muscle. We then review each of the ion channels in the myometrium: L- and T-type Ca channels, K (Kir6) channels, voltage-dependent K channels (Kv4, Kv7, and Kv11), twin-pore domain K channels (TASK, TREK), inward rectifier Kir7.1, Ca-activated K channels with large (KCNMA1, Slo1), small (KCNN1-3), and intermediate (KCNN4) conductance, Na-activated K channels (Slo2), voltage-gated (SCN) Na and Na leak channels, nonselective (NALCN) channels, the Na K-ATPase, and hyperpolarization-activated cation channels. We finish by assessing how three key hormones- oxytocin, estrogen, and progesterone-modulate and integrate excitability throughout gestation.
Topics: Animals; Female; Humans; Ion Channels; Membrane Proteins; Myocytes, Smooth Muscle; Myometrium; Pregnancy; Uterus
PubMed: 33158376
DOI: 10.1146/annurev-physiol-032420-035509