Menstrual Endometrium Research Articles

A protocol for creating endometriosis in rhesus macaques (Macaca mulatta).

Endometriosis is the presence of endometrium-like tissue outside the uterine cavity. An experimental model of endometriosis has been created in the baboon by the transcervical collection and laparoscopic inoculation of menstrual endometrium. Macaques are the preferred model for pharmaceutical development, but the complex anatomy of the macaque cervix makes the baboon method impractical. In this work, we sought to validate a surgical approach for creating endometriosis in macaques. Menstrual endometrium was collected via laparoscopic intrauterine puncture and transferred to the peritoneal cavity. We repeated this procedure during three menstruations. Endometriotic tissue was identified during laparoscopy, collected, and characterized by immunohistochemistry. Sham surgery-treated animals (n = 3) failed to develop endometriosis. We identified red, powder burnt, and white lesions in 13/14 of the treated animals; the stroma of the red lesions stained positive for ovarian steroid receptors. This surgical technique can reliably create hormone-responsive endometriosis in macaques for therapeutic studies.

HISTOMORPHOLOGICAL STUDY OF ENDOMETRIAL BIOPSIES OF PERIMENOPAUSAL WOMEN IN ABNORMAL UTERINE BLEEDING -A STUDY AT TERTIARY CARE CENTRE

Background: Abnormal uterine bleeding (AUB) is one of the common complaints in women in perimenopausal age group. Endometrial sampling is needed to investigate the cause of AUB. Aim: This study was conducted to evaluate the causes of AUB in perimenopausal age group and endometrial sampling by dilatation and curettage to identify various endometrial pathological patterns. Study Design: A type of prospective observational study conducted in department of pathology JMC Jhalawar. Materials And Methods: This study was done at the Department of Pathology, Jhalawar Medical College, Jhalawar during the period of one year from October 2020 to October 2021. Perimenopausal women (41-50 yrs.) with AUB who underwent dilatation and curettage were included in the study. Result: The commonest histopathological nding was secretory endometrium (38.33%) followed by proliferative endometrium (27.5%), hormonal imbalance (9.16%), simple hyperplasia without atypia (6.66%), disordered proliferative endometrium (5.83%) product of gestation (3.33%), menstrual endometrium (2.5%), chronic endometritis (1.66%) and endometrial polyp (0.83%). Endometrial carcinoma was diagnosed in 4 patients (3.33%). Conclusion: Endometrial causes of AUB evaluated by histopathological examination of curettings revealed that proliferative and secretory endometrium was the commonest diagnosis followed by hormonal imbalance.

Retinoic acid action is altered within endometrium of baboons affected with endometriosis

Objective: Using a baboon model, we determined the changing expression of Retinoic Acid (RA) target genes during the menstrual cycle and during disease progression. This change could explain the cellular response and changes characteristic of endometriosis. In previous studies, we established that endometriosis affects the CRABP2:FABP5 ratio in an in vitro environment, shifting toward apoptosis and differentiation with higher CRABP2, and anti-apoptosis with higher levels of FABP5. Intervention(s): Endometriosis was induced in female baboons with intraperitoneal inoculation of menstrual endometrium ( n = 2–4). Tissue was harvested via endometrectomy during different stages of the menstrual cycle as well at 3, 6, and 12 month timepoints after inoculation with endometriosis. Main outcome measure(s): Real time PCR was used to quantify STRA6 (a gene responsible for retinol uptake), CRABP2 (a gene necessary for apoptotic and anti-apoptotic estrogenic RA effects), and FABP5 (a gene that mediates the anti-apoptotic actions of RA). Results: STRA6 and CRABP2 expression were highest in the proliferative phase and lowest in the late secretory phase. FABP5 expression remained stable throughout the 12 months following the induction of the disease, whereas STRA6 and CRABP2 continued to decrease during the same period. Conclusions: Our study confirms that a shift in the CRABP2:FABP5 ratio has similar in vivo effects as it does in vitro: changing RA expression with disease induction and progression. As CRABP2 may be important in determining cell fate in the endometrium, gene expression changes could contribute to the anti-apoptotic behavior of affected cells. As expression changes more during progression, earlier rather than later treatment becomes more critical in reducing the rate of disease progression.

Markers of human endometrial hypoxia can be detected in vivo and ex vivo during physiological menstruation.

STUDY QUESTIONCan markers of human endometrial hypoxia be detected at menstruation in vivo?SUMMARY ANSWEROur in vivo data support the presence of hypoxia in menstrual endometrium of women during physiological menstruation.WHAT IS KNOWN ALREADYCurrent evidence from animal models and human in vitro studies suggests endometrial hypoxia is present at menstruation and drives endometrial repair post menses. However, detection of human endometrial hypoxia in vivo remains elusive.STUDY DESIGN, SIZE, DURATIONWe performed a prospective case study of 16 women with normal menstrual bleeding.PARTICIPANTS/MATERIALS, SETTING, METHODSReproductively aged female participants with a regular menstrual cycle underwent objective measurement of their menstrual blood loss using the alkaline haematin method to confirm a loss of <80 ml per cycle. Exclusion criteria were exogenous hormone use, an intrauterine device, endometriosis or fibroids >3 cm. Participants attended for two MRI scans; during days 1–3 of menstruation and the early/mid-secretory phase of their cycle. The MRI protocol included dynamic contrast-enhanced MRI and T2* quantification. At each visit, an endometrial sample was also collected and hypoxia-regulated repair factor mRNA levels (ADM, VEGFA, CXCR4) were quantified by RT-qPCR.MAIN RESULTS AND THE ROLE OF CHANCEWomen had reduced T2* during menstrual scans versus non-menstrual scans (P = 0.005), consistent with menstrual hypoxia. Plasma flow (Fp) was increased at menstruation compared to the non-menstrual phase (P = 0.0005). Laboratory findings revealed increased ADM, VEGF-A and CXCR4 at menstruation on examination of paired endometrial biopsies from the menstrual and non-menstrual phase (P = 0.008; P = 0.03; P = 0.009). There was a significant correlation between T2* and these ex vivo hypoxic markers (P < 0.05).LIMITATIONS, REASONS FOR CAUTIONThis study examined the in vivo detection of endometrial hypoxic markers at specific timepoints in the menstrual cycle in women with a menstrual blood loss <80 ml/cycle and without significant uterine structural abnormalities. Further research is required to determine the presence of endometrial hypoxia in those experiencing abnormal uterine bleeding with and without fibroids/adenomyosis.WIDER IMPLICATIONS OF THE FINDINGSHeavy menstrual bleeding (HMB) is a common, debilitating condition. Understanding menstrual physiology may improve therapeutics. To our knowledge, this is the first in vivo data supporting the presence of menstrual hypoxia in the endometrium of women with normal menstrual bleeding. If aberrant in those with HMB, these non-invasive tests may aid diagnosis and facilitate personalized treatments for HMB.STUDY FUNDING/COMPETING INTEREST(S)This work was funded by Wellbeing of Women grant RG1820, Wellcome Trust Fellowship 209589/Z/17/Z and undertaken in the MRC Centre for Reproductive Health, funded by grants G1002033 and MR/N022556/1. H.O.D.C. has clinical research support for laboratory consumables and staff from Bayer AG and provides consultancy advice (but with no personal remuneration) for Bayer AG, PregLem SA, Gedeon Richter, Vifor Pharma UK Ltd, AbbVie Inc; Myovant Sciences GmbH. H.O.D.C. receives royalties from UpToDate for articles on abnormal uterine bleeding.TRIAL REGISTRATION NUMBERN/A.

Genetic polymorphisms in eostrogen and progesterone receptor genes in &lt;i&gt;Papio anubis&lt;/i&gt; induced with endometriosis during early stage of the disease

<abstract> Genetic predisposition has been suggested to play a role in the pathogenesis of endometriosis. The most common pathogenetic hypotheses is that there is possible dysregulation of the ligand-receptorial signaling involving the main sex hormones, eostrogen and progesterone. This hypothesis indicates the need for studies to identify the genes and genomic variants involved in the pathogenesis of endometriosis. The present study investigated the genomic variants in eostrogen receptor 1 and progesterone receptor genes in baboons with induced endometriosis. Female adult olive baboons (n = 10) were induced with endometriosis by intraperitoneal inoculation of autologous menstrual endometrium. DNA was extracted from thirty plasma samples and analyzed by direct sequencing using gene specific primers to determine polymorphisms in eostrogen receptor 1 and progesterone receptor genes. To determine the single nucleotide polymorphisms, the DNA sequences were analyzed using Bioedit software. Twenty-six point mutations in eostrogen receptor 1 gene resulted to a change in amino acid (non-synonymous mutations) while thirteen had no effect on the amino acid sequence (synonymous mutations). There were two point mutations in progesterone gene although one had no effect on the amino acid sequence. Transition substitutions were more predominant than transversions in the eostrogen receptor 1 gene. These findings suggest that genetic variants of eostrogen receptor 1 gene are related to susceptibility to endometriosis and therefore this warrants further investigation on how they influence the disease pathogenesis. </abstract>

Abnormal uterine bleeding: A study of its clinical spectrum and incidence of histopathological patterns of endometrium as a function of age with parity

Introduction: Abnormal uterine bleeding (AUB) is a common complaint affecting majority of pre and postmenopausal women. Endometirum is a dynamic tissue and is affected by a wide range of histopathological lesions. The causes of AUB is a function of age. Aim and Objective: to study the histopathological pattern in cases of AUB in reference age, parity and bleeding pattern. Patients were categorized into reproductive (50 years). Materials and Methods: A total of three hundred patients presenting with AUB are included in this study. Observation and Results: In this study patient ranged from 20 to 70 years and the mean age of the cohort was 43.46±8.07. Major parity category noted in the cohort was para-2 in 89 patients (29.67%). Major bleeding pattern observed in the cohort was menorrhagia (32.33%); followed by metrorrhagia (19.67%), menometrorrhagia (16.33%), postmenopausal bleeding (12.67%), polymenorrhoea (9.67%), polymenorrhagia (5%) and continuous bleeding (1%). Histopathological pattern observed in AUB patients was proliferative phase endometrium (31.33%), secretory phase endometrium (21.67%), menstrual endometrium (1.33%). atrophic endometrium (6%), disordered proliferation (3.33%), mixed pattern (1%), polyp (10.67%), metaplasia (9.67%), hyperplasia (8.67%), endometritis (2.67%), adenocarcinoma (1.67%) and insufficient (2%). Conclusion: The causes of AUB are function of age; perimenopausal age group is the most common affected. Dilatation & Curettage is cost effective, useful procedure but organic lesions such as leiomyoma and adenomyosis can be missed. AUB is a common disorder affecting females and is a challenge to the treating gynaecologist. Keywords: Endometrium, Premenopausal, Postmenopausal, Hyperplasia, Polyp.

HYPOXIA AND REPRODUCTIVE HEALTH: The presence and role of hypoxia in the endometrium.

The endometrium is a multicellular tissue that is exquisitely responsive to the ovarian hormones. The local mechanisms of endometrial regulation to ensure optimal function are less well characterised. Transient physiological hypoxia has been proposed as a critical regulator of endometrial function. Herein, we review the literature on hypoxia in the non-pregnant endometrium. We discuss the pros and cons of animal models, human laboratory studies and novel in vivo imaging for the study of endometrial hypoxia. These research tools provide mounting evidence of a transient hypoxic episode in the menstrual endometrium and suggest that endometrial hypoxia may be present at the time of implantation. This local hypoxia may modify the inflammatory environment, influence vascular remodelling and modulate endometrial proliferation to optimise endometrial function. Finally, we review current knowledge of the impact of this hypoxia on endometrial pathologies, with a focus on abnormal uterine bleeding. Throughout the manuscript areas for future research are highlighted with the aim of concentrating research efforts to maximise future benefits for women and society.

Endometrial intravascular thrombi are typically associated with shedding but may be the sentinel feature of an underlying thrombotic disorder

Following the identification of endometrial intravascular thrombi (IVT) as the presenting feature in a patient with antiphospholipid syndrome, additional biopsy specimens were reviewed to determine the frequency and histological associations of IVT in the endometrium. Eighty-five additional biopsies were reviewed including 44 consecutive cases demonstrating shedding changes (both menstrual and non-cyclical), 30 cases without shedding (normal and non-cyclical), and 11 cases in which unusually prominent IVT had been recorded upon initial histological assessment. In the shedding group, IVT were significantly more common in biopsies showing disordered proliferative endometrium (DPE, 4/7 cases) than normal menstrual appearances (4/22 cases), and organising vascular changes were seen only in the former. IVT in DPE cases were also commonly multifocal and sometimes involved abnormal ectatic vessels. None of the 30 non-shedding cases demonstrated IVT. Eight of the 11 biopsies with prominent IVT demonstrated DPE and shedding but three cases demonstrated otherwise normal cyclical appearances. IVT may be seen occasionally in normal menstrual endometrium but are more characteristic of DPE, and organising vascular changes are suggestive of abnormal haemostasis. An underlying thrombotic disorder may be considered when endometrial IVT occur in the absence of shedding changes.

Correlation Between Endometrial Thickness By Ultrasonography and Histopathology in Abnormal Uterine Bleeding

Background : Abnormal uterine bleeding (AUB) is the most common presenting complaint of patients in Gynaecology Outpatient department. Early diagnosis of endometrial hyperplasia through ultrasongraphic measurement of endometrial thickness and definite diagnosis by histopathologic examination will help the clinicians to give appropriate treatment to the patients. The objective of this study was to correlate the histopathology findings in abnormal uterine bleeding with endometrial thickness by ultrasonography. Methods : This was a prospective study done from Nov 2016 to June 2018.A total of 382 cases of AUB presenting above 40 years of age were included. Endometrial thickness was measured by ultrasonography. Histopathological findings were studied and compared with the endometrial thickness. Statistical analysis were done using chi square test. Results : A total of 382 cases were analysed. Maximum number of cases were from peri menopausal age group (68.32%). Majority of the cases were due to non organic causes(85.34%). 46.86% of patients had endometrial thickness of 5-10mm followed by endometrial thickness of 11-15mm in 39.01%. Disordered proliferative endometrium was the most common pattern (38.34%) in our study followed by secretory endometrium (35.58%) and menstrual endometrium (18.71%). These findings were found to be statistically significant. Conclusion : A thorough histopathological work up and clinical correlation is mandatory in cases of abnormal uterine bleeding above 40 years to find out organic lesions. Careful screening can detect precursor lesions like endometrial hyperplasia and early cases of endometrial carcinoma which has excellent prognosis and it will help in further management.

Differential expression and functional analysis of micro RNAs in &lt;em&gt;Papio anubis&lt;/em&gt; induced with endometriosis for early detection of the disease

Endometriosis is a common gynecological disorder affecting approximately 10% of women of reproductive age who often experience chronic pelvic pain and infertility. Laparoscopy, which is invasive and expensive, is the gold standard for diagnosis of endometriosis. A simple minimally-invasive test for endometriosis-specific biomarkers which is yet to be realized would offer a timely and accurate diagnosis for the disease thereby allowing early treatment intervention. Although aberrant microRNA expression has been implicated in endometriosis in several studies, conflicting results have been reported. This study hypothesized that the use of an appropriate animal model will provide a unique entry point for the discovery of biomarkers for early diagnosis of endometriosis. The study aimed at identifying miRNAs that are differentially expressed in eutopic endometrium of induced endometriosis in Papio anubis for early detection of endometriosis. Female adult baboons (n = 3) were induced with endometriosis by intraperitoneal inoculation of autologous menstrual endometrium. We sequenced small RNA samples obtained from normal (control) and diseased eutopic endometrium. Quality reads from the sequences were subjected to differential expression analysis to identify dysregulated microRNAs and genes from other non-coding small RNA in the samples using a bioinformatics approach. Through in-silico analysis, gene targets of the dysregulated miRNA and their functions were determined. Our findings show significant high expression of seven microRNAs namely miR-199a-3p, miR-145-5p, miR-214-3p, miR-143-3p, miR-125b-5p, miR-199a-5p and miR-10b-5p. The study also reveals five microRNAs that were significantly down regulated and they include miR-29b-3p, miR-16-5p, miR-342-3p, miR-378a-3p and let-7g-5p. Seventeen genes from non-coding small RNAs were significantly dysregulated. The dysregulated microRNAs and genes play important roles in pathogenesis of endometriosis. Our findings indicate that specific miRNA signatures are associated with endometriosis, and the dysregulated miRNAs could constitute new and informative biomarkers for early diagnosis of endometriosis.

Investigation on endometrium from menstrual blood as a source of non-invasive tissue

Objective: To investigate the feasibility of a non-invasive sampling method by collecting menstrual blood and obtaining endometrium for further research in menstruation-related diseases. Methods: On the second day of menstruation, menstrual blood was collected with menstrual cups for 4 hours, and the menstrual endometrium was filtered through a metal screen for weighing, cryopreserved, immunohistochemical staining and cell culture. Results: The collection process was painless and non-invasive. In the control group, the menstrual volume was (9.1±0.7) ml, and the endometrial tissue weight was (91.0±14.7) g. In the endometriosis group, the menstrual volume was (9.6±1.9) ml (P=0.022), and the endometrial tissue weight was (134.7±43.9) g (P=0.057). Endometrial cell culture was successful in all patients and should not be contaminated. The growth curve was a finite cell line type. The expression of cytokeratin 19 and vimentin in menstrual endometrium and cells were positive. Conclusions: By collecting menstrual blood and filtering endometrial tissue, it is an ideal non-invasive sampling method. In combination with advanced experimental technology, menstrual endometrium make further researches of endometriosis, endometrial lesions or other menstruation-related diseases possible.

DETERMINATION OF ANTIGEN LEVELS: T-PLASTIN, TRANSGELIN AND CA-125 IN BABOONS WITH INDUCED ENDOMETRIOSIS

Endometriosis is defined as the presence of endometrial-like tissue outside the uterine cavity and is associated with chronic intra-pelvic inflammation. Its symptoms, which are often severe, have a negative impact on a woman’s quality of life. They include chronic pelvic pain and infertility. It is estimated that about 10% women in their reproductive ages are affected by the disease globally. Currently, diagnostic methods are laparoscopy with histological confirmation and non-invasive such as ultrasound and the quantification of CA-125 biomarker in serum. CA-125 is known to be elevated in endometriosis, however it does not have sufficient diagnostic power as a single biomarker of endometriosis. Due to this, there is a need to determine other antigens that would act as potential biomarkers for endometriosis. It has been observed that Transgelin and T-Plastin are upregulated in endometriosis lesions and in secretory phase of endometrium respectively. There is insufficient data available showing the concentration of T-plastin in serum or plasma in the development of endometriosis. The main objective of this study was to identify whether T-plastin, Transgelin and CA-125 are potential biomarkers in early diagnosis of endometriosis using animal model for endometriosis. The baboon model represents clinically relevant research models for endometriosis. This study compared the levels of T-plastin, Transgelin and CA-125 in the peripheral blood and peritoneal fluid of baboons before and after induction of endometriosis. In this prospective, case-control study, ten female baboons ( Papio anubis , 9-15 kg each) of proven fertility that have had at least one menstruation during captivity, were induced by intra-pelvic injection of menstrual endometrium on day 1 or 2 of menstruation followed by staging laparoscopy. Serum and peritoneal fluid samples were collected prior to induction to serve as controls.T-Plastin, Transgelin and CA-125 were measured using commercially available ELISA Kits. Data was analyzed using non-parametric test and level of significance at p&lt;0.005. T-Plastin and Transgelin had insignificant p values in both peripheral blood and peritoneal fluid while CA-125 showed p=0.0003 in peripheral blood and p=0.0279 in peritoneal fluid. Diagnostic performance of individual biomarkers was determined by Receiver Operating Characteristic (ROC) with the Area under the curve (AUC) equal to 0.5 showing T-Plastin and Transgelin in both serum and peritoneal fluid unreliable for use as biomarkers in endometriosis. CA-125 levels in peritoneal fluid had an AUC of 0.7900 indicating it can be used as potential biomarkers for endometriosis. Key words: Endometriosis, biomarkers, T-Plastin, Transgelin, CA-125, ELISA, Olive Baboons. DOI : 10.7176/ALST/75-06 Publication date :August 31 st 2019

Alterations in the Calcitonin and Calcitonin modulated proteins, E-cadherin and the enzyme tissueTransglutaminase II during the window of implantation in a baboon model of endometriosis

Endometriosis is a gynecological condition associated with infertility. We have previously demonstrated dysregulation of several molecular markers of uterine receptivity in a baboon model of induced endometriosis. Specifically, reduced levels of endometrial progesterone receptor (PR) and progesterone (P)-regulated genes, HOXA10 and FKBP52 were observed during the window of uterine receptivity in baboons with endometriosis, suggesting that this disease results in the development of an endometrial P resistance. In this study calcitonin (CALC) and CALC-modulated proteins, E-cadherin (E-Cad) and tissue Transglutaminase (tTgase-2) were evaluated in the eutopic endometrium of endometriotic animals throughout disease progression. Endometriosis was induced in normal cycling baboons by intraperitoneal inoculation of menstrual endometrium. Eutopic and ectopic endometrium was harvested consecutively from each animal at 1, 6 and 15 months of disease, during the window of receptivity. Control eutopic endometrium was s...

Hypoxia and hypoxia inducible factor-1\u03b1 are required for normal endometrial repair during menstruation

Heavy menstrual bleeding (HMB) is common and debilitating, and often requires surgery due to hormonal side effects from medical therapies. Here we show that transient, physiological hypoxia occurs in the menstrual endometrium to stabilise hypoxia inducible factor 1 (HIF-1) and drive repair of the denuded surface. We report that women with HMB have decreased endometrial HIF-1α during menstruation and prolonged menstrual bleeding. In a mouse model of simulated menses, physiological endometrial hypoxia occurs during bleeding. Maintenance of mice under hyperoxia during menses decreases HIF-1α induction and delays endometrial repair. The same effects are observed upon genetic or pharmacological reduction of endometrial HIF-1α. Conversely, artificial induction of hypoxia by pharmacological stabilisation of HIF-1α rescues the delayed endometrial repair in hypoxia-deficient mice. These data reveal a role for HIF-1 in the endometrium and suggest its pharmacological stabilisation during menses offers an effective, non-hormonal treatment for women with HMB.

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.

Reduced Transforming Growth Factor-β Activity in the Endometrium of Women With Heavy Menstrual Bleeding.

Context:Heavy menstrual bleeding (HMB) is common and incapacitating. Aberrant menstrual endometrial repair may result in HMB. The transforming growth factor (TGF)-β superfamily contributes to tissue repair, but its role in HMB is unknown.Objective:We hypothesized that TGF-β1 is important for endometrial repair, and women with HMB have aberrant TGF-β1 activity at menses.Participants/Setting:Endometrial biopsies were collected from women, and menstrual blood loss objectively measured [HMB >80 mL/cycle; normal menstrual bleeding (NMB) <80 mL].Design:Immunohistochemistry and reverse transcription polymerase chain reaction examined endometrial TGF-β1 ligand, receptors, and downstream SMADs in women with NMB and HMB. The function and regulation of TGF-β1 were examined using cell culture.Results:TGFB1 mRNA was maximal immediately prior to menses, but no differences detected between women with NMB and HMB at any cycle stage. Histoscoring of TGFB1 revealed reduced staining in the stroma during menses in women with HMB (P < 0.05). There were no significant differences in TGFBR1/2 or TGFBR1/2 immunostaining. Cortisol increased activation of TGFB1 in the supernatant of human endometrial stromal cells (HES; P < 0.05) via thrombospondin-1. Endometrial SMAD2 and SMAD3 were lower in women with HMB during menstruation (P < 0.05), and decreased phosphorylated SMAD2/3 immunostaining was seen in glandular epithelial cells during the late secretory phase (P < 0.05). Wound scratch assays revealed increased repair in HES cells treated with TGF-β1 versus control (P < 0.05).Conclusions:Women with HMB had decreased TGF-β1 and SMADs perimenstrually. Cortisol activated latent TGF-β1 to enhance endometrial stromal cell repair. Decreased TGF-β1 activity may hinder repair of the denuded menstrual endometrium, resulting in HMB.

Spatial and temporal characterization of endometrial mesenchymal stem-like cells activity during the menstrual cycle

The human endometrium is a highly dynamic tissue with the ability to cyclically regenerate during the reproductive life. Endometrial mesenchymal stem-like cells (eMSCs) located throughout the endometrium have shown to functionally contribute to endometrial regeneration. In this study we examine whether the menstrual cycle stage and the location in the endometrial bilayer (superficial and deep portions of the endometrium) has an effect on stem cell activities of eMSCs (CD140b+CD146+ cells). Here we show the percentage and clonogenic ability of eMSCs were constant in the various stages of the menstrual cycle (menstrual, proliferative and secretory). However, eMSCs from the menstrual endometrium underwent significantly more rounds of self-renewal and enabled a greater total cell output than those from the secretory phase. Significantly more eMSCs were detected in the deeper portion of the endometrium compared to the superficial layer but their clonogenic and self-renewal activities remained similar. Our findings suggest that eMSCs are activated in the menstrual phase for the cyclical regeneration of the endometrium.

MicroRNA Profiles in Spontaneous Decidualized Menstrual Endometrium and Early Pregnancy Decidua with Successfully Implanted Embryos.

To comparatively analyze the human microRNA (miRNA) profiles between spontaneous decidualized menstrual endometrium and early pregnancy decidua by an in-depth sequencing of miRNAs. The specific miRNAs expressed at conception might be involved in pregnancy establishment and expression of let-7f-5p and let-7g-5p was experimentally up-regulated or inhibited to assess the effect on the expression of IGF2BP-1 and IGF2R in vitro, respectively. Samples of endometria and deciduas were obtained from 25 women who suffered from tubal or male factor subfertility and from 35 early pregnant women who underwent pregnancy termination at 6–8 weeks gestation were irrespectively collected and comparatively analyzed by miRNA sequencing and differential expression of known and novel miRNAs was analyzed using bioinformatics. The 2042 miRNA expression was analyzed in the study and the differential expression of six miRNAs was validated by qRT-PCR. The expression of four miRNAs in decidua samples was down-regulated (miR-34c, miR-92a, miR-181a-5p, and miR-191), whereas the expression of miR-10a-5p and let-7f-5p was significantly up-regulated. The expression of IGF2BP-1 and IGF2R declined and increased with overexpression and inhibition of let-7f-5p and let-7g-5p, respectively. Changes in the expression of particular miRNAs might play a role in the physiology of decidualization following successful embryo implantation, ultimately resulting in continuous decidualization.

Endometrial Curettage When and for Who

In this study, the histopathological diagnoses pertaining to curettage material and the clinical necessity and results of endometrial curettagein age groups of patients in our region who had curettage due to abnormal uterine bleeding were studied. Thehistopathological diagnoses of patients with the above-mentioned criteria were scanned, excluding those related to pregnancy. 409 cases were re-examined and evaluated by a group consisting of three pathologists. Diagnoses were classified into 10 different groups. According to this classification system, out of the total number of cases, 100 were defined as endometrial polyp (24.4%), 72 cases as secretory endometrium (17.6%), 59 cases as proliferative endometrium (14.4%), 51 cases as stromal/glandular degeneration (12.5%), 32 cases as irregular proliferation (7.8%), 26 cases as insufficient (6.4%), 22 cases as chronic endometritis (5.6%), 18 cases as decidualization (4.4%), 17 cases as endometrial hyperplasia (complex atypical)/ adenocarcinoma (4.2%), and 12 cases as others (inactive, atrophic, basal and menstrual endometrium) (2.9%). The average age of the 409 cases was 44.8±7.8. Upon evaluation of curettage due to abnormal uterine bleeding in the approximate 3 year period in our region, and taking into consideration the age distribution, it was observed that the clinical pre-diagnoses of patients especially with endometrial polyps and precancerous lesions were coherent with the corresponding histopathological diagnoses.

CYTOKINE SECRETION BY ENDOMETRIAL STROMAL HUMAN CELLS FROM MENSTRUATION AND DECIDUA STROMAL HUMAN CELLS FROM PLACENTAS COLLECTED OF VAGINAL AND CAESAREAN DELIVERIES.

CYTOKINE SECRETION BY ENDOMETRIAL STROMAL HUMAN CELLS FROM MENSTRUATION AND DECIDUA STROMAL HUMAN CELLS FROM PLACENTAS COLLECTED OF VAGINAL AND CAESAREAN DELIVERIES.