Sampson's Theory Research Articles

Endometriosis: Molecular Pathophysiology and Recent Treatment Strategies-Comprehensive Literature Review.

Endometriosis is an enigmatic disease, with no specific cause or trigger yet discovered. Major factors that may contribute to endometriosis in the pelvic region include environmental, epigenetic, and inflammatory factors. Most experts believe that the primary mechanism behind the formation of endometrial lesions is associated with Sampson's theory of "retrograde menstruation". This theory suggests that endometrial cells flow backward into the peritoneal cavity, leading to the development of endometrial lesions. Since this specific mechanism is also observed in healthy women, additional factors may be associated with the formation of endometrial lesions. Current treatment options primarily consist of medical or surgical therapies. To date, none of the available medical therapies have proven effective in curing the disorder, and symptoms tend to recur once medications are discontinued. Therefore, there is a need to explore and develop novel biomedical targets aimed at the cellular and molecular mechanisms responsible for endometriosis growth. This article discusses a recent molecular pathophysiology associated with the formation and progression of endometriosis. Furthermore, the article summarizes the most current medications and surgical strategies currently under investigation for the treatment of endometriosis.

The Antigen-Processing Pathway via Major Histocompatibility Complex I as a New Perspective in the Diagnosis and Treatment of Endometriosis.

Endometriosis is a debilitating gynecological disease defined as the presence of endometrium-like epithelium and/or stroma outside the uterine cavity. The most commonly affected sites are the pelvic peritoneum, ovaries, uterosacral ligaments, and the rectovaginal septum. The aberrant tissue responds to hormonal stimulation, undergoing cyclical growth and shedding similar to appropriately located endometrial tissue in the uterus. Common symptoms of endometriosis are painful periods and ovulation, severe pelvic cramping, heavy bleeding, pain during sex, urination and bowel pain, bleeding, and pain between periods. Numerous theories have been proposed to explain the pathogenesis of endometriosis. Sampson's theory of retrograde menstruation is considered to be the most accepted. This theory assumes that endometriosis occurs due to the retrograde flow of endometrial cells through the fallopian tubes during menstruation. However, it has been shown that this process takes place in 90% of women, while endometriosis is diagnosed in only 10% of them. This means that there must be a mechanism that blocks the immune system from removing endometrial cells and interferes with its function, leading to implantation of the ectopic endometrium and the formation of lesions. In this review, we consider the contribution of components of the Major Histocompatibility Complex (MHC)-I-mediated antigen-processing pathway, such as the ERAP, TAP, LMP, LNPEP, and tapasin, to the susceptibility, onset, and severity of endometriosis. These elements can induce significant changes in MHC-I-bound peptidomes that may influence the response of immune cells to ectopic endometrial cells.

Laparoscopic Management of Innumerable Diaphragmatic Fenestrations

A 50-year-old woman known to have severe endometriosis was referred with cyclic pelvic pain, right shoulder pain, and recurring bilateral pleural effusions necessitating near-monthly thoracentesis of up to one liter of fluid. Gonadotrophin-releasing hormone agonism produced incomplete success. Diaphragmatic endometriosis is a condition affecting 1.5% of patients with endometriosis [1]. The mechanism postulated combines Sampson's theory of retrograde menstruation with clockwise transport of endometrial cells into the right subdiaphragmatic space via peritoneal fluid [1].

Menstruation Dysregulation and Endometriosis Development.

Endometriosis is a common gynecological condition characterized by the growth of endometrial-like tissue outside of the uterus which may cause symptoms such as chronic pelvic pain or subfertility. Several surgical and medical therapies are available to manage symptoms, but a cure has yet to be determined which can be attributed to the incomplete understanding of disease pathogenesis. Sampson's theory of retrograde menstruation is a widely accepted theory describing how shed endometrial tissue can enter the peritoneal cavity, but other factors are likely at play to facilitate the establishment of endometriosis lesions. This review summarizes literature that has explored how dysregulation of menstruation can contribute to the pathogenesis of endometriosis such as dysregulation of inflammatory mediators, aberrant endometrial matrix metalloproteinase expression, hypoxic stress, and reduced apoptosis. Overall, many of these factors have overlapping pathways which can prolong the survival of shed endometrial debris, increase tissue migration, and facilitate implantation of endometrial tissue at ectopic sites. Moreover, some of these changes are also implicated in abnormal uterine bleeding and endometrial diseases. More research is needed to better understand the underlying mechanisms driving dysregulation of menstruation in endometriosis specifically and identifying specific pathways could introduce new treatment targets. Analyzing menstrual fluid from women with endometriosis for inflammatory markers and other biomarkers may also be beneficial for earlier diagnosis and disease staging.

Revisiting Sampson's theory for hydrodynamic transport in ultrathin nanopores

Sampson's theory for hydrodynamic resistance across a zero-length orifice was developed over a century ago. Although a powerful theory for entrance/exit resistance in nanopores, it lacks accuracy for relatively small-radius pores since it does not account for the molecular interface chemistry. Here, Sampson's theory is revisited for the finite slippage and interfacial viscosity variation near the pore wall. The corrected Sampson's theory can accurately predict the hydrodynamic resistance from molecular dynamics simulations of ultrathin nanopores.6 MoreReceived 19 February 2020Accepted 1 October 2020DOI:https://doi.org/10.1103/PhysRevResearch.2.043153Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI.Published by the American Physical SocietyPhysics Subject Headings (PhySH)Research AreasFlows in porous mediaGeophysical fluid dynamicsGranular flowsInteratomic & molecular potentialsInterfacial flowsMicrofluidicsVan der Waals interactionFluid DynamicsAtomic, Molecular & Optical

Surgical Correction and Rehabilitation of Patients with Congenital Uterovaginal Anomalies and Concomitant Genital Endometriosis

Study Objective To evaluate the results of surgical treatment and rehabilitation in patients with uterovaginal anomalies and concomitant external genital endometriosis. Design Prospective cohort study. Level II-1. Setting Federal State Budget Institution «Research Center for Obstetrics, Gynecology and Perinatology» Ministry of Healthcare of the Russian Federation. Patients or Participants Since 2013 to 2019 we examined 198 patients with various uterovaginal anomalies. The 1st group included 105 patients with concomitant endometriosis, the 2d consisted of 93 patients without endometriosis. Interventions Surgical treatment of uterovaginal anomalies was made according to the anatomical type of malformation, clinical manifestations and reproductive outcomes. In cases with concomitant endometriosis we made excision and coagulation of endometriotic lesions. Measurements and Main Results The prevalence of primary infertility was significantly higher in 1st group- 55.5%, compared with the 2d group - 25.3% (p = 0.0057). The index of dysmenorrhea was significantly higher in 1-st group - 53.3%, compared with the control group -36, 6% (p = 0.0179). The frequency of external genital endometriosis was 53%. In 20% of patients with aplasia of the uterus and vagina without functional rudimental horns endometriotic lesions were visualized on pelvic peritoneum. Conclusion The laparoscopy revealed no significant differences in the incidence of endometriosis among patients with and without outflow obstruction of menstrual blood. Sampson's theory of retrograde menstruation doesn't explain the development of endometriosis in all patients with uterovaginal anomalies. Comprehensive treatment, including surgical correction of the anatomic type of malformation, with incision and coagulation of endometriotic lesions helped to get pregnancy in 60% of patients.

Ureaplasma Urealyticum Infection Contributes to the Development of Pelvic Endometriosis Through Toll-Like Receptor 2.

Endometriosis is a chronic gynecological disorder, characterized by the presence of ectopic endometrial tissue outside the uterine cavity. Among several hypotheses, Sampson's theory of retrograde menstruation is still applicable. Recent studies have reported the importance of inflammation among endometrial tissue, the peritoneum, and immune cells. However, less is known regarding the role of bacterial infection in the pathophysiology of endometriosis. We hypothesized that Ureaplasma urealyticum infection might contribute to the development of endometriosis by inducing the production of inflammatory mediators by peritoneal mesothelial cells (PMCs), possibly through TLR2. Hence, our objective was to reveal whether PMC infection by U. urealyticum is associated with endometriosis. Moreover, we aimed to demonstrate the molecular mechanism involved in this relationship. We developed a new infection-induced mouse model of endometriosis with wild type and Tlr2-deficient mice. Based on the in vivo mouse model, U. urealyticum-infected mice showed significantly increased numbers and sizes of ectopic endometriotic lesions. U. urealyticum upregulated not only the production of IL-6, CXCL1, and CCL2, but also the expression of ICAM-1, VCAM-1, and MMP2 in murine PMCs. Similarly, endometrial stromal cells dose-dependently produced IL-6, CXCL1, and CCL2 in response to U. urealyticum infection. The series of inflammatory responses in PMCs was mediated mainly through TLR2. The phosphorylation of ERK and JNK was observed when U. urealyticum was added to PMCs and knock out of Tlr2 inhibited these MAPKs phosphorylation. Based on our co-culture study, U. urealyticum-infected PMCs exhibited significantly increased attachment to ESCs compared with uninfected PMCs. Collectively, U. urealyticum infection promotes the development of endometriosis by increasing inflammatory mediators, adhesion molecules, and MMP-2 expression in PMCs through TLR2 signaling. Through our results, we present a theory that infection-induced pelvic inflammation contributes to the initiation and progression of endometriosis. Appropriate treatment of reproductive tract infection may decrease the prevalence of endometriosis.

Of Mice and Women: A Laparoscopic Mouse Model for Endometriosis

Study ObjectiveTo demonstrate how a novel laparoscopic approach allows the development of a mouse model for endometriosis after seeding menstrual endometrium from donor mice into the abdominal cavity of syngeneic recipient mice. DesignA step-by-step video description of the techniques used to adapt the estrous cycle of mice towards a menstrual cycle and to subsequently induce endometriosis via laparoscopic seeding of menstrual endometrium. SettingUniversity research institute. EthicsAll animal experiments were ethically approved by KU Leuven, Belgium (ethical approval number: P031/2013). Interventions, Measurements, and Main ResultsOophorectomized female C57BL/6JRj mice received a series of estrogen injections. Next, a progesterone pellet was administered, together with a second series of estrogen injections. In addition, decidualization of the endometrium was induced with an intrauterine sesame oil stimulus. Four days later the progesterone pellet was removed and menstruation started [1]. Five hours after the progesterone pellet was removal the uterus was harvested, and the menstrual endometrium was dissected and seeded into the abdominal cavity of syngeneic recipient mice to induce endometriosis [2] using a laparoscopic approach [3]. Uterus and lesions were removed from the recipient mice 1 week after induction, and tissues were immunohistochemically stained for H&E, vimentin, and cytokeratin. ConclusionIn this video we show a novel methodology to induce endometriosis in mice using laparoscopic inoculation of syngeneic menstrual endometrium, mimicking Sampson's theory of retrograde menstruation [4]. Compared with currently available rodent models, our model offers a less invasive and more physiologic way for fundamental and preclinical endometriosis research, with a high endometriosis incidence and lesion take rate.

PreImplantation Factor in endometriosis: A potential role in inducing immune privilege for ectopic endometrium.

Endometriosis is a chronic inflammatory condition characterised by the growth of endometrial epithelial and stromal cells outside the uterine cavity. In addition to Sampson’s theory of retrograde menstruation, endometriosis pathogenesis is facilitated by a privileged inflammatory microenvironment, with T regulatory FoxP3+ expressing T cells (Tregs) being a significant factor. PreImplantation Factor (PIF) is a peptide essential for pregnancy recognition and development. An immune modulatory function of the synthetic PIF analog (sPIF) has been successfully confirmed in multiple animal models. We report that PIF is expressed in the epithelial ectopic cells in close proximity to FoxP3+ stromal cells. We provide evidence that PIF interacts with FoxP3+ cells and modulates cell viability, dependent on cell source and presence of inflammatory mediators. Our finding represent a novel PIF-based mechanism in endometriosis that has potential for novel therapeutics.

The Presence of Endometrial Cells in Peritoneal Fluid of Women With and Without Endometriosis

To reinforce Sampson's theory of retrograde menstruation in the pathogenesis of endometriosis, proof should be provided that during menstruation endometrial cells are present in peritoneal fluid (PF). We hypothesize that the prevalence of PF samples containing endometrial cells is higher in patients with endometriosis than in controls without endometriosis during menstruation. We selected from our biobank PF samples of 17 reproductive-age women with (n = 9) or without (n = 8) endometriosis who had received a diagnostic laparoscopy for investigation of pain/infertility. Peritoneal fluid had been collected during laparoscopy in the menstrual phase of the cycle, centrifuged, and the resulting pellet was stored at -80°C. About 5-(j,m sections of frozen PF pellets were stained using the Dako Envision Flex system with primary antibodies against epithelial cell adhesion molecule (Ep-CAM; endometrial epithelial cells), CD 10 (endometrial stromal cells), prekeratin (epithelial/mesothelial cells), vimentin (endometrial/mesothelial/immune cells), calretinin (mesothelial cells), and CD68 (macrophages). The PF cells positive for Ep-CAM were detected in 5 of 9 patients with endometriosis and 6 of 8 controls (P =.62). CD10 stained positively in 6 of the 9 patients with endometriosis and 3 of the 8 controls (P =.35). Calretinin and prekeratin staining showed the presence of mesothelial cells in all pellets. Vimentin stained approximately 100% of the PF cells. CD68+ macrophages represented >50% of cells in all pellets. The prevalence of PF samples containing endometrial epithelial and stromal cells was not higher in patients with endometriosis than in controls without endometriosis during menstruation. Our findings question the relevance of endometrial cells in PF for the pathogenesis of endometriosis and support the importance of other mechanisms such as immune dysfunction and/or endometrial stem cells.

Role of Versican in the Pathogenesis of Peritoneal Endometriosis.

Sampson's theory cannot explain why only some cycling women develop peritoneal endometriosis. Few studies have focused on the pelvic peritoneum, which receives regurgitated endometrial tissues. We hypothesized that molecular alterations in the peritoneum are involved in the development of peritoneal endometriosis and conducted a microarray analysis to compare macroscopically normal peritoneum sampled from women with peritoneal endometriosis (endometriotic peritoneum) and those without (non-endometriotic peritoneum). Versican, a major proteoglycan component of the extracellular matrix, is one of the molecules up-regulated in endometriotic peritoneum. To investigate the role of versican in peritoneal endometriosis. Design, Patients, and Main Outcome Measure: Endometriotic peritoneum and non-endometriotic peritoneum were subjected to RT-PCR, immunostaining, and Western blotting. The versican V1 isoform was stably transfected into Chinese hamster ovary cells (CHO-V1), and the effects of CHO-V1-derived conditioned medium (V1-CM) on primary human endometrial stromal cells were investigated with attachment, invasion, and proliferation assays. The effects of peritoneal fluid collected from endometriotic women (endometriotic PF) or cytokines/growth factors, which were shown to be elevated in endometriotic PF, on versican expression in a human peritoneal cell line (HMrSV5) were also examined. Versican V1 expression levels were significantly higher in endometriotic peritoneum. In vitro, V1-CM promoted attachment to the HMrSV5 cell monolayer as well as the Matrigel invasion of endometrial stromal cells. Although versican V1 expression was up-regulated by TGF-β1 in HMrSV5 cells, it remained unchanged in endometriotic PF. Our results suggest the involvement of peritoneal versican in the development of peritoneal endometriosis.

Making it on the Outside: Towards an Integrated Control Theory for Understanding the Reintegration Process

Reintegration has garnered greater attention in criminology, as many releasees from prisons are being recycled back into criminal justice systems around the world. Despite this trend, the reintegration literature to date has been mainly descriptive and few studies have paid attention to the theoretical dynamics and social context surrounding reintegration. To address this gap, we suggest that the prominent debate, mainly found in American criminology, on crime causation between Gottfredson and Hirschi's (1990) General Theory of Crime (GTC) and Sampson and Laub's (1993) and Laub and Sampson's (2003) Age-Graded Theory of Informal Social Control (AGTISC) be used to advance this largely atheoretical literature. After showing that research exploring the effects of self-control and informal social control on reintegration remains largely uncharted territory in criminological theory, we propose an integrated control theory, in addition to some methodological considerations, for better understanding reintegration.

Rebels without regret: documentary artivism in the digital age

This article takes up the implications of the blurring of art and politics in two documentary contexts: Ai Weiwei's art activism in China, as documented in Alison Klayman's award-winning film Never Sorry, and the Gezi protests in Turkey, documented and disseminated virally through the Internet. Drawing parallels between the self-proclaimed hooliganism of Ai Weiwei and the Turkish protesters, who co-opted the hooligan label that the government used to incriminate them and turned it into a tool for resistance, the article argues that hooliganism is just another incarnation of unruly documentary artivism, which has become prevalent in an era of digitally mediated, global social justice movements. As an interpretive framework for understanding how documentary hooliganism operates, the article proposes Tony D. Sampson's theory of virality and its application of Dawkins's neo-Darwinian memetic thought contagion model to the way ideas and political gestures spread in the twenty-first century. Hooliganism, like viruses or memetic thoughts, has a self-spreading tendency; its anarchic affect is contagious and creates volatile yet powerful social encounters. Therefore, the article claims that the foregrounding of hooliganism, which is itself a phenomenon that describes ‘affective contagious encounters’ among anonymous crowds, in the artivist practices of Ai Weiwei and Turkish protesters point to the potential of unruly forms of documentation to influence and inspire self-organized mobilization.

Agency as a Cause of Crime

Laub and Sampson's age-graded theory of social control posits that the greater is a person's agency, the less that person commits crime. But agency has a dark side as well. Some people choose to offend in order to transform their life; when this happens, agency is a cause of crime. In the present article we draw on the life course and rational choice perspectives to explore this idea. Our study is based on qualitative data obtained through interviews with and observations of offenders from socially disadvantaged areas in Cape Town, South Africa. Participants cited their offending as motivated by and effective in obtaining three kinds of status: belonging in a group, respect from peers, and wealth. Further research is needed to develop understanding of this relationship, especially in terms of how it is affected by structural conditions and culture.

Distribution of CD44 (cluster of differentiation-44) positive endometrial epithelial progenitors in human endometriosis

Sampson's theory of retrograde menstruation remains the leading hypothesis for the pathogenesis of endometriosis. While most reproductive age women experience retrograde menstruation, the prevalence of endometriosis is only 7-10%. We hypothesize that endometriosis results from defects in the stem cell niche, causing more shedding of endometrial progenitors. Recently our group identified CD44 as one marker for isolation of endometrial epithelial progenitors (Stem Cells 2012, 4:808-22). The purpose of this study was to assess if uterine epithelial progenitor cells marked by CD44 are present at increased frequencies in ectopic endometrial implants.

Ovarian steroid alter endometrial epithelial cell attachment to peritoneal mesothelial cells

Sampson's theory suggests that endometrial cells(ECs) transported retrograde through the fallopian tubes implant on peritoneal mesothelial cells (PMCs) to initiate the development of early endometriotic lesions (ELs). While ovarian steroids are primary regulators of established ELs, little is known about their role in the initial attachment of ECs to PMCs. Here, we assessed the effect of estradiol (E2) and progesterone (P4) on menstrual epithelial cell (EEC) attachment to PMC using an established model.

Peritoneal excision of endometriosis: just a surgical technique or cure of disease?

The purpose of this work is to demonstrate that aggressive complete regional peritoneal excision of endometriosis has a high cure rate with minimal risk and therefore is a superior procedure. Retrospective Review. Patients included were treated at a busy referral endometriosis practice from July of 1994 through April of 2013 who had undergone complete aggressive regional peritoneal excision for endometriosis followed by a second laparoscopy or laparotomy. Detailed surgical drawings were made at each surgery demonstrating areas of disease, adhesions and resection. Of the original 1823, five (0.28%) were found to have true recurrence of disease inside the prior resection margin. Lesion number in this group ranged 1-6. Fifteen patients (0.82%) were found have new disease. Of the 65 patients that met inclusion criteria with second surgery, time between the two surgeries averaged 43 months with a range of 2-170 months. Of those 60/65 (92%) of patients had no evidence of recurrence inside resection margins and 45/65 (69%) were completely disease free. In patients with disease present at the second surgery, 85% had stage 3 or greater disease at the first surgery. Sixty-five percent of these high stage patients had their stage reduced to stage 1. Endometriomas caused all cases of persistent stage 3-4 disease. While there are cases in this series of noted disease in areas where the peritoneum was previously removed (true recurrence), this was unusual and the number of lesions found in patients with former high stage disease, post op adhesion formation and complication rate was very low. This with long surgical intervals strongly suggests Sampson's theory of retrograde menstruation is not a likely etiology of endometriosis, rather surgical autografting is proposed. Aggressive regional peritoneal resection offers a safe method of surgical treatment with low post operative adhesion formation and a very high cure rate for primary disease even in higher stage disease.

Important Initiative Roles of CD44 and Tenascin in Sampson's Theory of the Pathogenesis and Development of Endometriosis

Background Among several theories explaining the pathogenesis of endometriosis, Sampson's theory seems to be the most reliable and popular. However, this theory does have some problems. First, the onset of endometriosis is not as common as retrograde menstruation. Second, the surface of the peritoneum is capable of preventing the adhesion of foreign bodies such as endometrial cells. Regarding the first problem, several studies on immunosurveillance have been reported. The second problems has not yet been clarified, Therefore we investigated the problem in the present report. Methods Levels of CD44 and tenascin in both menstrual and peripheral blood were assayed in 19 healthy volunteer women in the first experiment. In the second experiment, the effects of tenascin on the activity of MMP-9 were investigated, because the invasive ability of endometriotic cells is known to be due to MMP activity. Results CD44 and tenascin concentrations were significantly higher in menstrual blood than in peripheral blood. Since CD44 is a specific hyaluronic acid receptor, CD44 in menstrual blood was demonstrated to be a specific matchmaker of adhesion between the endometrial cells and the peritoneal surface. Tenascin in menstrual blood and endometriotic cells up-regulated MMP activity and promoted the invasive action of endometriotic cells. Conclusion The present study clarified that adhesion of endometrial cells in menstrual blood on adhesion-preventive peritoneal surface was achieved by a mediator, CD44, in menstrual blood and that the ability of endometriotic cells to invade, induced by MMP, was achieved through up-regulation of MMP activity by the mediator tenascin.

Identification of Cells with Colony-Forming Activity, Self-Renewal Capacity, and Multipotency in Ovarian Endometriosis

Endometriosis, the growth of endometrial tissue outside the uterine cavity, is a common gynecological disorder affecting 10% to 15% of women in their reproductive years. Retrograde menstrual shedding containing endometrial stem/progenitor cells has been postulated to be involved in its pathogenesis. In this study, we identified putative endometriotic stem/progenitor cells by their colony-forming potential, self-renewal capacity, and multipotency. Purified epithelial and stromal cells isolated from ovarian endometriotic cysts formed large and small colony-forming units (CFUs) in clonogenic assay. The colony-forming activity of epithelial and stromal cells was found to differ greatly between autologous endometrium and ovarian endometrioma samples. The large CFUs could propagate more than the small CFUs. The endometriotic epithelial small CFUs expressed epithelial markers (epithelial cell adhesion molecule, cytokeratin, and α6 integrin); only occasional large CFUs expressed α6 integrin. Aside from the expression of fibroblast markers, stromal CFUs also expressed three somatic stem cell markers: sal-like 4, CD133, and Musashi-1. Endometriotic stromal cells derived from large CFUs could differentiate into four mesenchymal lineages when cultured in the respective inducing-media, as determined by histochemical staining and RT-PCR of lineage specific markers. These findings demonstrate that ovarian endometrioma contains a subset of cells displaying somatic stem cell properties.

Evolving Spectrum:

Although the exact etiology of endometriosis is unknown, several hypotheses about its origin exist. Of these, Sampson's theory of retrograde menstruation is the most widely accepted. Multiple in-vitro and in vivo models have been developed to study endometriosis. Several key steps are required to establish an endometriotic implant: presence of ectopic endometrial glands and stroma, attachment of endometrial cells to the peritoneum, invasion into the mesothelium, and survival and growth of the ectopic tissue. Many of these steps are similar to those associated with neoplasia, and numerous biologic pathways are involved. It is likely that both intrinsic factors within the ectopic endometrium and permissive alterations within the host are important to the development of endometriosis.