Current concepts of the mechanisms of menstruation (original) (raw)

Menstrual physiology: implications for endometrial pathology and beyond

Human Reproduction Update, 2015

† Introduction † Methods † Results To bleed or not to bleed? Menstruation: a model of self-limiting inflammation? The endometrium: a model of vascular function The perimenstrual endometrium: a model of scarless tissue repair † Conclusions background: Each month the endometrium becomes inflamed, and the luminal portion is shed during menstruation. The subsequent repair is remarkable, allowing implantation to occur if fertilization takes place. Aberrations in menstrual physiology can lead to common gynaecological conditions, such as heavy or prolonged bleeding. Increased knowledge of the processes involved in menstrual physiology may also have translational benefits at other tissue sites. methods: Pubmed and Cochrane databases were searched for all original and review articles published in English until April 2015. Search terms included 'endometrium', 'menstruation', 'endometrial repair', 'endometrial regeneration' 'angiogenesis', 'inflammation' and 'heavy menstrual bleeding' or 'menorrhagia'. results: Menstruation occurs naturally in very few species. Human menstruation is thought to occur as a consequence of preimplantation decidualization, conferring embryo selectivity and the ability to adapt to optimize function. We highlight how current and future study of endometrial inflammation, vascular changes and repair/regeneration will allow us to identify new therapeutic targets for common gynaecological disorders. In addition, we describe how increased knowledge of this endometrial physiology will have many translational applications at other tissue sites. We highlight the clinical applications of what we know, the key questions that remain and the scientific and medical possibilities for the future. conclusions: The study of menstruation, in both normal and abnormal scenarios, is essential for the production of novel, acceptable medical treatments for common gynaecological complaints. Furthermore, collaboration and communication with specialists in other fields could significantly advance the therapeutic potential of this dynamic tissue.

The Menstrual Endometrium: From Physiology to Future Treatments

Frontiers in Reproductive Health, 2022

Abnormal uterine bleeding (AUB) is experienced by up to a third of women of reproductive age. It can cause anaemia and often results in decreased quality of life. A range of medical and surgical treatments are available but are associated with side effects and variable effectiveness. To improve the lives of those suffering from menstrual disorders, delineation of endometrial physiology is required. This allows an increased understanding of how this physiology may be disturbed, leading to uterine pathologies. In this way, more specific preventative and therapeutic strategies may be developed to personalise management of this common symptom. In this review, the impact of AUB globally is outlined, alongside the urgent clinical need for improved medical treatments. Current knowledge of endometrial physiology at menstruation is discussed, focusing on endocrine regulation of menstruation and local endometrial inflammation, tissue breakdown, hypoxia and endometrial repair. The contribution...

Mechanism of normal menstruation and abnormality associated with menorrhagia

2001

Pada Inid nonnal terjadi peLuruhan jaringan endometium dan perdarahan, diikuti oLeh hemostasis dan 'repair'. Kelainan dapat terjadi pada berbagai tahap dari proses di atas, dan dapat mengakibatkan perubahan jumlah darah haid. Haid dengan jumlah darah lebih dari 80 ml disebut menorhagia. Sari pustaka ini membicarakan meknnisme haid normal, dan berbagai faktor yang berkaitatt dengan menorhagia. Faktor tersebut adalah 'endometrial bleeding associated factor (ebaf)', peran berbagai sel (lekosit migran, makrofag, dan sel mnst), peran berbagai zat (enzim lisosom, berbagai prostaglandin, endotelin, faktor pertumbuhan, dan reseptornya), gangguan padafibrinolisis dan proses hemostasis, dan perubahan aliran darah endometrium. (Med J Irulones 2001; Abstract Notmal menstruation involves endometrial tissue breakdown and bleeding, followed by hemostasis and repair. Abnormality of this Process at any stage may resub in changes in the quantity of menstrual blood loss. When menstrual blood loss is greater thnn 80 ml, it is called menorhagia. This review discuss the mechanism of normal menstruation, and factors associated with menorrhagia. Those factors are the endometrial bleeding associatedfactor (ebaf), the role ofvarious cells (migratory leucocytes, macrophages, and mast cells), the role of various substances (lysosomal enzymes, prostaglandins, endothelins, growthfactors and its receptors), impairment of fibrinolysis and hemostatic proces, and changes in endometrial bloodflow. (Med J Indones 2001; 10: 12l-6)

Endometrial apoptosis and neutrophil infiltration during menstruation exhibits spatial and temporal dynamics that are recapitulated in a mouse model

Scientific reports, 2017

Menstruation is characterised by synchronous shedding and restoration of tissue integrity. An in vivo model of menstruation is required to investigate mechanisms responsible for regulation of menstrual physiology and to investigate common pathologies such as heavy menstrual bleeding (HMB). We hypothesised that our mouse model of simulated menstruation would recapitulate the spatial and temporal changes in the inflammatory microenvironment of human menses. Three regulatory events were investigated: cell death (apoptosis), neutrophil influx and cytokine/chemokine expression. Well-characterised endometrial tissues from women were compared with uteri from a mouse model (tissue recovered 0, 4, 8, 24 and 48 h after removal of a progesterone-secreting pellet). Immunohistochemistry for cleaved caspase-3 (CC3) revealed significantly increased staining in human endometrium from late secretory and menstrual phases. In mice, CC3 was significantly increased at 8 and 24 h post-progesterone-withdr...

Morphological changes in mesothelial cells induced by shed menstrual endometrium in vitro are not primarily due to apoptosis or necrosis

Human Reproduction, 2000

In a previous study on the pathogenesis of endometriosis, we observed that constituents of menstrual effluent induce morphological alterations in human mesothelial cells. In this study, we investigated whether these alterations were associated with apoptosis or necrosis or were the result of cellular remodelling. After overnight incubation of confluent monolayers of human omental mesothelial cells (HOMEC) with conditioned media prepared from menstrual effluent shed anterogradely, severe alterations in morphology were observed. Typical polygonal mesothelial cell cultures at confluency acquired elongated spindle morphology, resulting in gaps between the cells. In contrast, mesothelial cells from the control groups receiving culture medium only, retained a normal morphology. Immunofluorescence staining revealed that cytokeratin, vimentin and actin filaments were still present, homogeneously distributed in the cell cytoplasm following changes in morphology. To evaluate whether the morphological alterations were associated with apoptosis and/or necrosis, the cells were stained with the M30 CytoDeath antibody or annexin V with propidium iodide and analysed using flow cytometry. The results showed that only a small percentage (1-7%) of the affected HOMEC were undergoing apoptosis or necrosis. We conclude that the profoundly altered morphology of HOMEC is a result of cellular remodelling and that the role of apoptosis and necrosis is negligible. Soluble paracrine factors released by cells isolated from menstrual effluent shed anterogradely may induce a reorganization of the cytoskeleton. As a result, the underlying basement membrane will be exposed and the mesothelium may no longer prevent implantation of endometrium shed retrogradely into the peritoneum, thus facilitating the development of endometriosis.

Paracrine regulation of menstruation

Journal of Reproductive Immunology, 1998

Endometrial proliferation, secretion, vascular neoformation and modification to shedding is under direct and/or indirect control of steroid hormones. The progressive modification of the endometrial architecture is due to its growth and differentiation. The new tissue regenerates monthly from a 2-5 mm to a 12-18 mm of complex tissue until it sheds under a co-ordinated network of bioactive molecules produced and activated during the menstrual cycle. The steroid hormones, the HLA-DR and integrin molecules, the intense production of several proteins, the vascular damage, and the disconnection of cell-cell and cell-matrix interaction are participating in both the endometrial preparation for embryonic implantation and the shedding and bleeding of the tissue itself. Menstruation is a process associated with damage to the epithelium, endothelium and extracellular matrix, ending on controlled bleeding, tissue dissolution and repair. Endometrial proteinases and tissue factor (TF) contribute to systemic factors to control the mechanisms of regulation of tissue dissolution, tissue shedding, and vascular bleeding during menstruation.

Regulation and restricted expression of interstitial collagenase suggest a pivotal role in the initiation of menstruation

Human Reproduction, 1996

Collagenases are the only mammalian enzymes able to cleave, at neutral pH, the triple helical domain of fibrillar collagens, major constituents of the extracellular matrix of the endometrium. Interstitial collagenase is expressed, secreted and activated in human endometrium only just before and during menstruation. The expression of interstitial collagenase is restricted to the areas of the functional layer of the endometrium which are breaking down and to fragments which have been shed. In endometrial explants, combined sex steroids tightly control the expression, secretion and activation of interstitial collagenase, as well as the preservation of the extracellular matrix. These observations imply a pivotal role for this proteinase in the initiation of menstruation.

Endometrial immunocompetent cells in proliferative and secretory phase of normal menstrual cycle

Folia Morphologica, 2015

Background: Menstruation was presented as a result of inflammatory process. The total and relative numbers of the endometrial immunocompetitive cells vary during the different phases of the menstrual cycle. The aim of this morphological study is to make a contribution in understanding different distribution of leukocyte types during proliferative and secretory phase of normal menstrual cycle. 2 Materials and methods: The study included 40 women (20 in proliferative and 20 in secretory phase of the menstrual cycle). Exploratory curettage performed as preoperative preparation due to uterine myomas. Immunophenotyping was performed by immunoalkaline phosphatase (APAAP) using monoclonal antibodies: CD15, CD 20, CD30, CD45 RO, CD56, CD57 and CD68. The results were statistically analyzed using SPSS 20.0 software. Results: NK cells are dominant during secretory, and CD45RO T lymphocytes are dominant during proliferative phase of the menstrual cycle. During the secretory phase of menstrual cycle, leukocytes make 30% of total endometrial cells. NK cells (CD56+ bright subpopulation), activated T lymphocytes, macrophages and B lymphocytes significant increase in their number during the secretory phase of menstrual cycle. Conclusions: Significantly changes in endometrial leukocyte populations during proliferative and secretory phase of the menstrual cycle are emphasized. Changes in dominance of different leukocyte subpopulations are determined by hormonal and microenvironmental changes in modulatory factors that have not yet been fully explained.