-
Endocrine Reviews Aug 2019Pelvic endometriosis is a complex syndrome characterized by an estrogen-dependent chronic inflammatory process that affects primarily pelvic tissues, including the... (Review)
Review
Pelvic endometriosis is a complex syndrome characterized by an estrogen-dependent chronic inflammatory process that affects primarily pelvic tissues, including the ovaries. It is caused when shed endometrial tissue travels retrograde into the lower abdominal cavity. Endometriosis is the most common cause of chronic pelvic pain in women and is associated with infertility. The underlying pathologic mechanisms in the intracavitary endometrium and extrauterine endometriotic tissue involve defectively programmed endometrial mesenchymal progenitor/stem cells. Although endometriotic stromal cells, which compose the bulk of endometriotic lesions, do not carry somatic mutations, they demonstrate specific epigenetic abnormalities that alter expression of key transcription factors. For example, GATA-binding factor-6 overexpression transforms an endometrial stromal cell to an endometriotic phenotype, and steroidogenic factor-1 overexpression causes excessive production of estrogen, which drives inflammation via pathologically high levels of estrogen receptor-β. Progesterone receptor deficiency causes progesterone resistance. Populations of endometrial and endometriotic epithelial cells also harbor multiple cancer driver mutations, such as KRAS, which may be associated with the establishment of pelvic endometriosis or ovarian cancer. It is not known how interactions between epigenomically defective stromal cells and the mutated genes in epithelial cells contribute to the pathogenesis of endometriosis. Endometriosis-associated pelvic pain is managed by suppression of ovulatory menses and estrogen production, cyclooxygenase inhibitors, and surgical removal of pelvic lesions, and in vitro fertilization is frequently used to overcome infertility. Although novel targeted treatments are becoming available, as endometriosis pathophysiology is better understood, preventive approaches such as long-term ovulation suppression may play a critical role in the future.
Topics: Animals; Endometriosis; Endometrium; Female; Humans; Mice; Receptors, Progesterone; Stromal Cells; Uterine Diseases
PubMed: 30994890
DOI: 10.1210/er.2018-00242 -
Fertility and Sterility Mar 2021Congenital and acquired uterine anomalies are associated with recurrent pregnancy loss (RPL). Relevant congenital Müllerian tract anomalies include unicornuate,... (Review)
Review
Congenital and acquired uterine anomalies are associated with recurrent pregnancy loss (RPL). Relevant congenital Müllerian tract anomalies include unicornuate, bicornuate septate, and arcuate uterus. Recurrent pregnancy loss has also been associated with acquired uterine abnormalities that distort the uterine cavity such as, notably, intrauterine adhesions, polyps, and submucosal myomas. Initial evaluation of women with RPLs should include an assessment of the uterine anatomy. Even if proof of efficacy of surgical management of certain uterine anomalies is often lacking for managing RPLs, surgery should be encouraged in certain circumstances for improving subsequent pregnancy outcome. Uterine anomalies such as uterine septa, endometrial polyps, intrauterine adhesions, and submucosal myomas are the primary surgical indications for managing RPLs.
Topics: Abortion, Habitual; Female; Humans; Hysteroscopy; Pregnancy; Urogenital Abnormalities; Uterus
PubMed: 33712099
DOI: 10.1016/j.fertnstert.2020.12.003 -
International Journal of Molecular... Sep 2021Endometriosis is a "mysterious" disease and its exact cause has not yet been established. Among the etiological factors, congenital, environmental, epigenetic,... (Review)
Review
Endometriosis is a "mysterious" disease and its exact cause has not yet been established. Among the etiological factors, congenital, environmental, epigenetic, autoimmune and allergic factors are listed. It is believed that the primary mechanism of the formation of endometriosis foci is retrograde menstruation, i.e., the passage of menstrual blood through the fallopian tubes into the peritoneal cavity and implantation of exfoliated endometrial cells. However, since this mechanism is also observed in healthy women, other factors must also be involved in the formation of endometriosis foci. Endometriosis is in many women the cause of infertility, chronic pain and the deterioration of the quality of life. It also represents a significant financial burden on health systems. The article presents a review of the literature on endometriosis-a disease affecting women throughout the world.
Topics: Adult; Cyclooxygenase 2; Cytokines; Endometriosis; Endometrium; Female; Gene Expression Regulation; Humans; Infertility, Female; Vascular Endothelial Growth Factor A
PubMed: 34638893
DOI: 10.3390/ijms221910554 -
International Journal of Molecular... Feb 2023Endometriosis is a complex disease, which is defined by abnormal growth of endometrial tissue outside the uterus. It affects about 10% of women of reproductive age all... (Review)
Review
Endometriosis is a complex disease, which is defined by abnormal growth of endometrial tissue outside the uterus. It affects about 10% of women of reproductive age all over the world. Endometriosis causes symptoms that notably worsen patient's well-being-such as severe pelvic pain, dysfunction of the organs of pelvic cavity, infertility and secondary mental issues. The diagnosis of endometriosis is quite often delayed because of nonspecific manifestations. Since the disease was defined, several different pathogenetic pathways have been considered, including retrograde menstruation, benign metastasis, immune dysregulation, coelomic metaplasia, hormonal disbalance, involvement of stem cells and alterations in epigenetic regulation, but the true pathogenesis of endometriosis remains poorly understood. The knowledge of the exact mechanism of the origin and progression of this disease is significant for the appropriate treatment. Therefore, this review reports the main pathogenetic theories of endometriosis based on current studies.
Topics: Female; Humans; Endometriosis; Epigenesis, Genetic; Uterus; Infertility; Pelvis
PubMed: 36901685
DOI: 10.3390/ijms24054254 -
Molecules (Basel, Switzerland) Jun 2022Endometriosis is a gynecological condition characterized by the growth of endometrium-like tissues inside and outside the pelvic cavity. The evolution of the disease can... (Review)
Review
Endometriosis is a gynecological condition characterized by the growth of endometrium-like tissues inside and outside the pelvic cavity. The evolution of the disease can lead to infertility in addition to high treatment costs. Currently, available medications are only effective in treating endometriosis-related pain; however, it is not a targeted treatment. The objective of this work is to review the characteristics of the disease, the diagnostic means and treatments available, as well as to discuss new therapeutic options.
Topics: Endometriosis; Endometrium; Female; Humans; Manipulation, Osteopathic; Pain
PubMed: 35807280
DOI: 10.3390/molecules27134034 -
International Journal of Molecular... Jan 2022Changes in the female genital tract microbiome are consistently correlated to gynecological and obstetrical pathologies, and tract dysbiosis can impact reproductive... (Review)
Review
Changes in the female genital tract microbiome are consistently correlated to gynecological and obstetrical pathologies, and tract dysbiosis can impact reproductive outcomes during fertility treatment. Nonetheless, a consensus regarding the physiological microbiome core inside the uterine cavity has not been reached due to a myriad of study limitations, such as sample size and experimental design variations, and the influence of endometrial bacterial communities on human reproduction remains debated. Understanding the healthy endometrial microbiota and how changes in its composition affect fertility would potentially allow personalized treatment through microbiome management during assisted reproductive therapies, ultimately leading to improvement of clinical outcomes. Here, we review current knowledge regarding the uterine microbiota and how it relates to human conception.
Topics: Dysbiosis; Endometrium; Female; Fertilization; Humans; Microbiota; Pregnancy; Pregnancy Outcome; Virulence
PubMed: 35008911
DOI: 10.3390/ijms23010485 -
Fertility and Sterility Aug 2018Endometritis is subdivided into two categories. Acute endometritis is symptomatic and characterized by microabscess formation and neutrophil invasion in the endometrial... (Review)
Review
Endometritis is subdivided into two categories. Acute endometritis is symptomatic and characterized by microabscess formation and neutrophil invasion in the endometrial superficial epithelium, gland lumina, and uterine cavity. Chronic endometritis is rather silent and recognized as unusual plasmacyte infiltration in the endometrial stromal areas. Over the last decade, studies have disclosed the potential association between poor reproductive outcomes and endometritis, particularly chronic endometritis. The aim of this review is to address the current literature surrounding chronic endometritis and highlight recent advances in the research of this long-neglected gynecologic disease.
Topics: Anti-Bacterial Agents; Chronic Disease; Endometritis; Endometrium; Female; Humans; Infertility, Female; Microbiota; Pregnancy
PubMed: 29960704
DOI: 10.1016/j.fertnstert.2018.04.012 -
Fertility and Sterility Feb 2019To study the pathophysiology of endometriosis. (Review)
Review
OBJECTIVE
To study the pathophysiology of endometriosis.
DESIGN
Overview of observations on endometriosis.
SETTING
Not applicable.
PATIENT(S)
None.
INTERVENTIONS(S)
None.
MAIN OUTCOME MEASURE(S)
The hypothesis is compatible with all observations.
RESULT(S)
Endometriosis, endometrium-like tissue outside the uterus, has a variable macroscopic appearance and a poorly understood natural history. It is a hereditary and heterogeneous disease with many biochemical changes in the lesions, which are clonal in origin. It is associated with pain, infertility, adenomyosis, and changes in the junctional zone, placentation, immunology, plasma, peritoneal fluid, and chronic inflammation of the peritoneal cavity. The Sampson hypothesis of implanted endometrial cells following retrograde menstruation, angiogenic spread, lymphogenic spread, or the metaplasia theory cannot explain all observations if metaplasia is defined as cells with reversible changes and an abnormal behavior/morphology due to the abnormal environment. We propose a polygenetic/polyepigenetic mechanism. The set of genetic and epigenetic incidents transmitted at birth could explain the hereditary aspects, the predisposition, and the endometriosis-associated changes in the endometrium, immunology, and placentation. To develop typical, cystic ovarian or deep endometriosis lesions, a variable series of additional transmissible genetic and epigenetic incidents are required to occur in a cell which may vary from endometrial to stem cells. Subtle lesions are viewed as endometrium in a different environment until additional incidents occur. Typical cystic ovarian or deep endometriosis lesions are heterogeneous and represent three different diseases.
CONCLUSION(S)
The genetic epigenetic theory is compatible with all observations on endometriosis. Implications for treatment and prevention are discussed.
Topics: Animals; Endometriosis; Endometrium; Epigenesis, Genetic; Female; Genetic Markers; Genetic Predisposition to Disease; Heredity; Humans; Phenotype; Prognosis; Risk Factors
PubMed: 30527836
DOI: 10.1016/j.fertnstert.2018.10.013 -
International Journal of Molecular... Aug 2019In the healthy endometrium, progesterone and estrogen signaling coordinate in a tightly regulated, dynamic interplay to drive a normal menstrual cycle and promote an... (Review)
Review
In the healthy endometrium, progesterone and estrogen signaling coordinate in a tightly regulated, dynamic interplay to drive a normal menstrual cycle and promote an embryo-receptive state to allow implantation during the window of receptivity. It is well-established that progesterone and estrogen act primarily through their cognate receptors to set off cascades of signaling pathways and enact large-scale gene expression programs. In endometriosis, when endometrial tissue grows outside the uterine cavity, progesterone and estrogen signaling are disrupted, commonly resulting in progesterone resistance and estrogen dominance. This hormone imbalance leads to heightened inflammation and may also increase the pelvic pain of the disease and decrease endometrial receptivity to embryo implantation. This review focuses on the molecular mechanisms governing progesterone and estrogen signaling supporting endometrial function and how they become dysregulated in endometriosis. Understanding how these mechanisms contribute to the pelvic pain and infertility associated with endometriosis will open new avenues of targeted medical therapies to give relief to the millions of women suffering its effects.
Topics: Animals; Endometriosis; Endometrium; Estrogens; Female; Hormones; Humans; Infertility, Female; Progesterone; Receptors, Estrogen; Receptors, Progesterone; Signal Transduction; Steroids
PubMed: 31387263
DOI: 10.3390/ijms20153822 -
International Journal of Molecular... Apr 2023Endometriosis is a chronic inflammatory disease associated with bothersome symptoms in premenopausal women and is complicated with long-term systemic impacts in the... (Review)
Review
Endometriosis is a chronic inflammatory disease associated with bothersome symptoms in premenopausal women and is complicated with long-term systemic impacts in the post-menopausal stage. It is generally defined by the presence of endometrial-like tissue outside the uterine cavity, which causes menstrual disorders, chronic pelvic pain, and infertility. Endometriotic lesions can also spread and grow in extra-pelvic sites; the chronic inflammatory status can cause systemic effects, including metabolic disorder, immune dysregulation, and cardiovascular diseases. The uncertain etiologies of endometriosis and their diverse presentations limit the treatment efficacy. High recurrence risk and intolerable side effects result in poor compliance. Current studies for endometriosis have paid attention to the advances in hormonal, neurological, and immunological approaches to the pathophysiology and their potential pharmacological intervention. Here we provide an overview of the lifelong impacts of endometriosis and summarize the updated consensus on therapeutic strategies.
Topics: Female; Humans; Endometriosis; Inflammation; Endometrium; Pelvic Pain; Treatment Outcome
PubMed: 37108664
DOI: 10.3390/ijms24087503