Myometrial Layers Research Articles

Evaluation of morphology, apoptosis, and cell proliferation of the uterus in postmenopausal women.

The aim of this study was to evaluate the morphology (atrophy and fibrosis), apopto-sis, and cell proliferation in the uterine wall. The research material came from postmenopausal women who had undergone hysterectomy due to uterine myomas or prolapse of the reproductive organ and were not taking menopausal hormone therapy (MTH). The collected material was divided into three groups. Group I (n=18) con-sisted of uterine sections taken 1 to 5 years after the last menstruation, Group II (n=17) 6 to 10 years after the last menstruation, and Group III (n=15) over 11 years after the last menstruation. To assess morphology and fibrosis, the uterine sections were subjected to hematoxylin and eosin (HE) staining and to Mallory's staining. In addition, we performed a histochemical examination to identify apopto-sis in endometrial and myometrial cells using the TUNEL method. An immunohistochemical analysis of endometrial and myometrial cells was also performed to detect the location of the proliferating cell nuclear antigen (PCNA). Differences in apoptosis were only found in the myometrium between Group I and Group III, and were strongest in Group I myometrial cells, and weakest in Group III. Neither the endome-trium nor the myometrium showed statistically significant differences in the overall percentage of PCNA(+) cells between groups. Morphological changes in the endometrial and myometrial layers of postmenopausal uteri increased with time since the last menstruation.

Estrogen receptor alpha mediated repression of PRICKLE1 destabilizes REST and promotes uterine fibroid pathogenesis.

Uterine fibroids (leiomyomas), benign tumors of the myometrial smooth muscle layer, are present in over 75% of women, often causing severe pain, menorrhagia and reproductive dysfunction. The molecular pathogenesis of fibroids is poorly understood. We previously showed that the loss of REST (RE-1 Silencing Transcription factor), a tumor suppressor, in fibroids leads to activation of PI3K/AKT-mTOR pathway. We report here a critical link between estrogen receptor alpha (ERα) and the loss of REST, via PRICKLE1. PRICKLE1 expression is markedly lower in leiomyomas, and the suppression of PRICKLE1 significantly down regulates REST protein levels. Conversely, overexpression of PRICKLE1 resulted in the restoration of REST in cultured primary leiomyoma smooth muscle cells (LSMCs). Crucially, mice exposed neonatally to environmental estrogens, proven risk factors for fibroids, expressed lower levels of PRICKLE1 and REST in the myometrium. Using mice that lack either endogenous estrogen (Lhb -/- mice) or ERα (Esr1 -/- mice), we demonstrate that Prickle1 expression in the myometrium is suppressed by estrogen through ERα. Enhancer of zeste homolog 2 (EZH2) is known to participate in the repression of specific ERα target genes. Uterine leiomyomas express increased levels of EZH2 that inversely correlate with the expression of PRICKLE1. Using chromatin immunoprecipitation, we provide evidence for association of EZH2 with the PRICKLE1 promoter and for hypermethylation of H3K27 within the regulatory region of PRICKLE1 in leiomyomas. Additionally, siRNA mediated knockdown of EZH2 leads to restoration of PRICKLE1 in LSMCs. Collectively, our results identify a novel link between estrogen exposure and PRICKLE1/REST-regulated tumorigenic pathways in leiomyomas.

Insights into the role of PGF2α in canine periparturient myometrium.

Parturition in dogs is subjected to complex hormonal regulation, with the involvement of prostaglandin F2α (PGF2α) still not fully understood. To investigate uterine inertia (UI), the most prevalent maternal reason for dystocia in the bitch, a better understanding of undisturbed uterine, especially myometrial function, is crucial. Our aim was to gain deeper insights into the role of PGF2α in the canine parturient myometrium. Uterine biopsies were obtained during medically indicated cesarean sections. To test for stimulatory effects of PGF2α in vitro, circular and longitudinal myometrial layer tissue strips were challenged with 50pM, 0.5µM, and 50µM PGF2α. Prostaglandin-endoperoxide synthase 2 (PTGS2) and PGF2α-receptor (PTGFR) mRNA expressions were compared between primary UI (PUI) and obstructive dystocia (OD) samples in isolated parturient myometrium. PTGFR protein expression was assessed in full thickness uterine samples. PGF2α concentrations were analyzed in canine interplacental tissue around term. In the organ bath, the contractile response to PGF2α was limited to the circular layer at the highest dosage. Correspondingly, PTGFR immunohistochemical staining was significantly stronger in the circular layer (p ≤ 0.01). PTGS2 gene expression did not differ between PUI and OD, whereas PTGFR gene expression could not be quantified. Local uterine PGF2α concentrations correlated negatively with serum P4 levels and were the highest during prepartum luteolysis while being significantly lower in PUI. Conclusively, despite the significant increase in local PGF2α concentrations at birth, confirming the interplacental tissue as a production site, our results suggest that PGF2α might affect uterine contractility during labor, mainly indirectly.

Internal and external adenomyosis phenotypes: ultrasound features and association with clinical outcomes.

What are the sonographic and clinical findings in women diagnosed with external and internal adenomyosis by ultrasound? Patients with external and internal adenomyosis phenotypes, diagnosed by ultrasound, present differences in sonographic features of the disease and demographic characteristics including age, parity, and association with deep endometriosis (DE) and leiomyomas. Two different phenotypes of adenomyosis have been described based on the anatomical location of adenomyotic lesions in the myometrium, suggesting that adenomyosis affecting the inner myometrium and that affecting the external myometrial layer may have distinct origins. A cross-sectional study including 505 patients with a sonographic diagnosis of adenomyosis was performed between January 2021 and December 2022. Women sonographically diagnosed with adenomyosis in a tertiary referral hospital that serves as a national reference center for endometriosis were included over a 2-year period. Patients were divided into two groups (internal and external adenomyosis) according to the myometrial layer affected by adenomyosis. We compared sonographic and clinical outcomes including a multivariate analysis between the two groups. According to ultrasound findings, 353 (69.9%) patients presented with internal adenomyosis, while 152 (30.1%) presented with external adenomyosis. Women with internal adenomyosis were significantly older and less frequently nulliparous compared to those with external adenomyosis. Sonographically, internal adenomyosis appeared diffusely, it had a greater number of adenomyosis features, it presented a globular morphology of the uterus more frequently, and it coexisted with leiomyomas more frequently, compared to external adenomyosis. Conversely, the presence of translesional vascularity and associated DE were more common among the external adenomyosis group. No significant differences were found between internal and external adenomyosis groups regarding pain, heavy menstrual bleeding, spotting, or infertility. In the multivariate analysis, nulliparity, the presence of leiomyomas, and the presence of DE were independently associated with adenomyosis phenotypes (the presence of DE and nulliparity increased the risk of external adenomyosis, whereas the presence of leiomyomas was a risk factor for internal adenomyosis). Considering the impact of hormonal treatment, we found that the number of ultrasound adenomyosis criteria was significantly greater in patients without hormonal treatment. Non-treated patients more commonly presented dysmenorrhea or bleeding-associated pain and heavy menstrual bleeding than women on hormonal treatment, although there were no significant differences according to adenomyosis phenotypes. As the population was selected from the Endometriosis Unit of a tertiary center, there may be patient selection bias, given the high prevalence of individuals with associated endometriosis, previous endometriosis-related surgery, and/or receiving hormonal treatment. Transvaginal ultrasound is the most available and cost-effective tool for the diagnosis of adenomyosis. Adenomyosis phenotypes based on ultrasound findings may be key in achieving an accurate diagnosis and in decision-making regarding the most adequate therapeutic strategy for the management of patients with adenomyosis. Determination of the sonographic features associated with symptoms could help in the evaluation of treatment response. No funding was obtained for this study and there are no conflicts of interest to declare. N/A.

Localization of Catecholaminergic Neurofibers in Pregnant Cervix as a Possible Myometrial Pacemaker.

In eutocic labor, the autonomic nervous system is dominated by the parasympathetic system, which ensures optimal blood flow to the uterus and placenta. This study is focused on the detection of the quantitative presence of catecholamine (C) neurofibers in the internal uterine orifice (IUO) and in the lower uterine segment (LUS) of the pregnant uterus, which could play a role in labor and delivery. A total of 102 women were enrolled before their submission to a scheduled cesarean section (CS); patients showed a singleton fetus in a cephalic presentation outside labor. During CS, surgeons sampled two serial consecutive full-thickness sections 5 mm in depth (including the myometrial layer) on the LUS and two randomly selected samples of 5 mm depth from the IUO of the cervix. All histological samples were studied to quantify the distribution of A nerve fibers. The authors demonstrated a significant and notably higher concentration of A fibers in the IUO (46 ± 4.8) than in the LUS (21 ± 2.6), showing that the pregnant cervix has a greater concentration of A neurofibers than the at-term LUS. Pregnant women's mechanosensitive pacemakers can operate normally when the body is in a physiological state, which permits normal uterine contractions and eutocic delivery. The increased frequency of C neurofibers in the cervix may influence the smooth muscle cell bundles' activation, which could cause an aberrant mechano-sensitive pacemaker activation-deactivation cycle. Stressful circumstances (anxiety, tension, fetal head position) cause the sympathetic nervous system to become more active, working through these nerve fibers in the gravid cervix. They might interfere with the mechano-sensitive pacemakers, slowing down the uterine contractions and cervix ripening, which could result in dystocic labor.

Type and Location of Adenomyosis in Women with Recurrent Pregnancy Loss: A Transvaginal Ultrasonographic Assessment.

The current knowledge on adenomyosis as a risk factor for RPL is very scant. Overall 120 women were included in this retrospective observational study. They were divided in three groups each of which consisted of 40 subjects: Group 1: women with RPL who were diagnosed to have adenomyosis on transvaginal ultrasound (TVS); Group 2: patients with RPL without ultrasonographic findings of adenomyosis; Group 3: patients with ultrasound diagnosis of adenomyosis without RPL and at least one live birth pregnancy. The copresence of endometriosis was also investigated. Among women with RPL, patients with adenomyosis (Group 1) had higher number of pregnancy losses (p = 0.03) and lower age at first pregnancy loss (p = 0.03) than women without adenomyosis (Group 2). Moreover, they had more frequently primary RPL (p = 0.008). Adenomyosis of the inner myometrium was found more frequently (p = 0.04) in patients of Group 1 than in patients of Group 3 in which adenomyosis was mainly in the outer myometrium (p= 0.02). No differences were found in the severity of adenomyosis between these two groups of women. TVS findings for endometriosis were observed more frequently in women with adenomyosis without RPL (Group 3) than in the other two groups of patients. Adenomyosis can be a factor involved in RPL. Differences in adenomyosis localization are associated with different risks for RPL. Patients with RPL should be investigated for the presence of adenomyosis and also for the type and localization of the disease in the different myometrial layers.

Progress of the study of pericytes and their potential research value in adenomyosis.

Pericytes (PCs) are versatile cells integral to the microcirculation wall, exhibiting specific stem cell traits. They are essential in modulating blood flow, ensuring vascular permeability, maintaining homeostasis, and aiding tissue repair process. Given their involvement in numerous disease-related pathological and physiological processes, the regulation of PCs has emerged as a focal point of research. Adenomyosis is characterized by the presence of active endometrial glands and stroma encased by an enlarged and proliferative myometrial layer, further accompanied by fibrosis and new blood vessel formation. This distinct pathological condition might be intricately linked with PCs. This article comprehensively reviews the markers associated with PCs, their contributions to angiogenesis, blood flow modulation, and fibrotic processes. Moreover, it provides a comprehensive overview of the current research on adenomyosis pathophysiology, emphasizing the potential correlation and future implications regarding PCs and the development of adenomyosis.

Chronic exposure of mice to phthalates enhances TGF beta signaling and promotes uterine fibrosis

Phthalates are synthetic chemicals widely used as plasticizers and stabilizers in various consumer products. Because of the extensive production and use of phthalates, humans are exposed to these chemicals daily. While most studies focus on a single phthalate, humans are exposed to a mixture of phthalates on a regular basis. The impact of continuous exposure to phthalate mixture on uterus is largely unknown. Thus, we conducted studies in which adult female mice were exposed for 6 months to 0.15 ppm and 1.5 ppm of a mixture of phthalates via chow ad libitum. Our studies revealed that consumption of phthalate mixture at 0.15 ppm and 1.5 ppm for 6 months led to a significant increase in the thickness of the myometrial layer compared to control. Further investigation employing RNA-sequencing revealed an elevated transforming growth factor beta (TGF-β) signaling in the uteri of mice fed with phthalate mixture. TGF-β signaling is associated with the development of fibrosis, a consequence of excessive accumulation of extracellular matrix components, such as collagen fibers in a tissue. Consistent with this observation, we found a higher incidence of collagen deposition in uteri of mice exposed to phthalate mixture compared to unexposed controls. Second Harmonic Generation (SHG) imaging showed disorganized collagen fibers and nanoindentation indicated a local increase in uterine stiffness upon exposure to phthalate mixture. Collectively, our results demonstrate that chronic exposure to phthalate mixture can have adverse effects on uterine homeostasis.

Transvaginal Ultrasound Evaluation Of Cesarean Section Niche Scar During Pregnancy: A Prospective Longitudinal Study

Background and Objectives: To determine the prevalence of a CS scar niche during pregnancy using transvaginal ultrasound imaging, and to determine the relationship between the evolution of the CS scar niche and the ultimate pregnancy result. Materials and Methods: Transvaginal sonography was used in this prospective observational research to look at the uterine scars of 100 women at 11+0-13+6, 18+0-20+6 and 32+0-35+6 weeks of pregnancy. When the region of hypoechogenic myometrial discontinuity of the lower uterine section was discovered, a scar was discernible while pregnant. An indentation at the location of the CS scar with a depth of at least 2 mm in the sagittal axis was designated as the CS scar niche (or "defect"). Myometrial thickness next to the niche and the remaining myometrial thickness were used to quantify the hypoechogenic portion of the CS niche in two dimensions. (RMT). The entire lower uterine segment (LUS) thickness and the myometrial layer thickness were measured during the second and third trimesters of pregnancy at the thinnest portion of the scar area. In a non-selected subset of patients (n=20), CS scars were measured by two separate examiners. Scar visibility was evaluated using descriptive analysis, and the intraclass correlation coefficient (ICC) was computed to demonstrate the degree of absolute agreement between two observers for measuring scars. Maternal age, BMI, smoking status, prior vaginal deliveries, obstetric complications, and a history of uterine curettage were among the factors looked into as potential contributors to the CS scar niche. The hospital's computerized medical database provided clinical statistics on pregnancy outcomes and complications. Results: 80.9% of the ladies could see the scar. A CS scar niche was prevalent in 53.6% of people with a noticeable CS scar. Excellent intra- and interobserver agreement was observed for CS scar niche readings. There was no statistically significant correlation between maternal age, BMI, gestational diabetes, smoking status, previous vaginal delivery after CS, and niche development when subgroups of women were compared in terms of CS scar niche and non-niche. In contrast to 34.4 % of the women who did not have uterine curettage, 56.3% of the women who had done uterine curettage had uterine scar niches. Conclusions: The CS scar niche could be reproducibly measured by a transvaginal scan in half of the cases with a visible CS scar at the first trimester of pregnancy, according to an ultrasonography evaluation. An increased chance of uterine niche formation in a subsequent pregnancy was linked to prior uterine curettage. The CS scar area may be connected to uterine scar dehiscence.

New boundaries for fertility sparing management in endometrial cancer.

The increasing rates of endometrial cancer in premenopausal women that accompanies modern lifestyle options that enhance the prevalence of obesity as well as the trend of delayed childbearing are expected to increase the need for fertility sparing techniques. Currently, the cornerstone of fertility sparing treatment is hormonal handling with progestin treatment and is reserved for women with well differentiated endometrioid lesions that are limited in the myometrial layer. Innovative approaches in the surgical treatment of patients with the use of operative hysteroscopy seem to offer decreased intervals to remission of lesions and longer progression free survival. Recent small case series also dictate that patients with endometrioid lesions of medium differentiation as well as those with superficial myometrial invasion may be adequately treated with the use of operative hysteroscopy. Moreover, the novel classification system may help better understand patients that will likely respond better to hormonal treatment. In the near future, further data from clinical trials will be available that will help optimize patient selection as well select surgical and medical options that will help establish a personalized approach of fertility preservation in endometrial cancer patients.

Endometrioid Carcinoma of the Uterine Corpus With a Micropapillary Component: A Novel Prognostic Factor For Metastasis.

Micropapillary pattern is a morphologically distinctive form of carcinoma composed of small, hollow, or morula-like clusters of cancer cells surrounded by clear stromal spaces. The neoplastic cells characteristically display a reverse polarity, also known as an ''inside-out'' growth pattern, that is linked to higher frequencies of lymphovascular invasion and lymph nodal metastasis. To the best of our knowledge, it has not been previously recognized in uterine corpus. We report 2 cases of endometrioid carcinoma of the uterine corpus with a micropapillary component. In these cases, histological examination identified an endometrioid carcinoma that had invaded the myometrial layer. The carcinoma cells that constructed the micropapillary components were immunohistochemically positive for EMA. They lined the stromal facing surface of the cell membrane, confirming the inside-out growth pattern, and D2-40 immunohistochemistry confirmed lymphovascular invasion of carcinoma cells. We believe that the micropapillary pattern linked to higher frequencies of lymphovascular invasion and lymph nodal metastasis may be one of the most important invasive patterns in endometrioid carcinomas of the uterine corpus for predicting aggressive malignant potential, prognosis, and recurrence, although further, larger studies are required to evaluate its clinical significance.

Placenta Accreta Spectrum Diagnosis Challenges and Controversies in Current Obstetrics: A Review.

Placenta accreta spectrum (PAS) is the most common obstetric complication in current obstetrics in which the placenta is fully or partially attached to the uterine myometrial layer at delivery. This is commonly due to the deficiency of the uterine interface between the uterine endometrial and myometrial layers leading to abnormal decidualization at the uterine scar area, which permits the abnormally placental anchoring villous and trophoblasts, deeply invade the myometrium. The prevalence of PAS is globally at rising trends every day in modern obstetrics originally due to the high increasing rate of cesarean sections, placenta previa, and assisted reproductive technology (ART). Thus, the early and precise diagnosis of PAS is imperative to prevent maternal intrapartum or postpartum bleeding complications. The main aim of this review is to debate the current challenges and controversies in the routine diagnosis of PAS diseases in obstetrics. We retrospectively reviewed the recent articles on different methods of diagnosing PAS in PubMed, Google Scholar, Web of Science, Medline, Embase, and other website databases. Despite that, the standard ultrasound is a reliable and key tool for the diagnosis of PAS, the lack of ultrasound features does not exclude the diagnosis of PAS. Therefore, clinical assessment of risk factors, MRI tests, serological markers, and placental histopathological tests are also indispensable for the prediction of PAS. Previously, limited studies reached a high sensitivity rate of diagnosis PAS in appropriate cases, while many studies recommended the inclusion of different diagnosis methods to improve the diagnosis accuracy. A multidisciplinary squad with well-experienced obstetricians, radiologists, and histopathologists should be involved in the establishment of the early and conclusive diagnosis of PAS.

Bilateral Cornual Resection for Uterine-sparing Removal of Tubal Sterilization Devices

To describe a uterine-sparing minimally invasive surgical technique for laparoscopic resection of tubal occlusion devices using bilateral cornuectomy. This video reviews the background of the tubal occlusion device known as Essure, as well as the indications and methods for surgical removal with a stepwise demonstration of a minimally invasive technique with narrated video footage. The most cited reason for patients' desire for removal of the Essure device is pelvic pain. Both hysteroscopic and laparoscopic methods have been utilized for removal of these devices. Laparoscopy is indicated if it has been greater than three months since insertion, if a coil is noted to be malpositioned, or if the patient desires continued permanent sterilization. Techniques for removal include salpingostomy, salpingectomy, and cornuectomy. Removal of the entire device is essential, as any remaining coil or polyethylene terephthalate (PET) fibers may continue to cause symptoms. The coils of the device can easily be fractured; therefore, in our practice we perform a bilateral cornuectomy when uterine retention is desired, as fracture rates are higher with salpingectomy compared with cornuectomy. We demonstrate the steps of this method and highlight the critical aspects for surgeons to consider during the procedure. Laparoscopic bilateral cornuectomy approach to a uterine-sparing excision of Essure tubal occlusion devices to reduce the risk of coil retention and fracture: 1) Injection of dilute vasopressin at the uterine cornua for vasoconstriction and hemostasis 2) Circumferential dissection of the uterine cornua using monopolar energy 3) Confirmation of endometrial cavity entry using methylene blue 4) Excision of fallopian tube along mesosalpinx to include the fimbriated end 5) Closure of the myometrial layers using a unidirectional barbed suture in a running fashion CONCLUSION: In patients who desire uterine preservation, we recommend a minimally invasive technique of bilateral cornual resection for removal of tubal sterilization devices in order to avoid device fracture and inadvertent retention of coils.

Current Non-Invasive Imaging Techniques Used in the Diagnosis of Adenomyosis

Objective: This review aims to provide insights into the current non-invasive imaging methods used in the diagnosis of adenomyosis, as well as to highlight their diagnostic accuracy, advantages, disadvantages and limitations in the detection of this benign uterine condition. At the same time, this paper emphasizes the importance of using consensus-based terminology in the imaging description of these lesions. Mechanism: A search of PUBMED database was conducted for articles published between January 1998 and August 2022 and studies which compared non-invasive imaging methods with postoperative histology examination of uterine specimens were primarily selected. Transvaginal two-dimensional ultrasound was for a long time the main non-invasive imagistic method used for assessment of adenomyosis lesions. The introduction of Morphological Uterus Sonographic Assessment (MUSA) group criteria yielded a significantly better diagnostic outcome of adenomyosis in case of conventional ultrasonography, but the distinction of concomitant benign uterine conditions still remained challenging. Findings in Brief: The addition of three-dimensional ultrasound or elastosonography to conventional two-dimensional transvaginal ultrasound yielded higher diagnostic sensitivity. Qualitative elastography particularly proved useful in the diagnosis of adenomyosis due to its capacity to achieve differential diagnosis of benign uterine pathologies based on lesion stiffness. Magnetic resonance imaging (MRI) examination presents higher diagnostic specificity and sensitivity, can assess the endometrial and myometrial layers in detail, but its use has been shadowed by costs and significantly longer examination time. Conclusions: The imaging terminology established by consensus by the MUSA group in recent years has facilitated the description of adenomyosis-specific lesions. Two-dimensional transvaginal ultrasound in combination with three-dimensional ultrasound or combined with qualitative elastography offers similar diagnostic sensitivity and specificity to MRI. Despite some limitations, MRI remains a reliable diagnostic method for adenomyosis.

Management of interstitial pregnancy using laparoscopic salpingectomy with complete removal of the interstitial portion

To perform laparoscopic salpingectomy, including the entire interstitial portion of the fallopian tube, in the management of interstitial pregnancy. A step-by-step explanation of the surgical procedure using video with narration. Obstetrics and Gynecology department of a hospital. A 23-year-old woman, gravida 1 para 0, presented asymptomatically to our hospital to undergo a pregnancy test. Her last menstrual period had occurred 6 weeks previously. Transvaginal ultrasound showed an empty uterine cavity and a right interstitial mass of 3.2 × 2.6 × 2.5 cm. It contained a chorionic sac and an embryonic bud of 0.2 cm long with a heartbeat and the presence of an "interstitial line sign." The myometrial layer surrounding the chorionic sac was 1 mm. The patient's beta-human chorionic gonadotropin level was 10,123 mIU/mL. On the basis of the anatomy of the interstitial portion of the fallopian tube, we treated interstitial pregnancy using laparoscopic salpingectomy, with complete removal of the interstitial portion containing the product of conception. The interstitial fallopian tube originates at the tubal ostium and follows a tortuous intramural course, progressing laterally away from the uterine cavity toward the isthmic portion. It is lined by muscular layers and an inner epithelium layer. The main blood supply of the interstitial portion is from the uterine artery's ascending branches to the fundus, extending a branch that supplies the cornu and the interstitial portion. Our approach has 3 key steps: 1) dissecting and coagulating the branch extending from the ascending branches to the fundus of the uterine artery, 2) incising the cornual serosa at the junction of the purple-blue interstitial pregnancy and the normal color myometrium, and 3) resecting the interstitial portion containing the product of conception along the outer layer of the oviduct without rupture. The interstitial portion containing the product of conception was removed entirely along the outer layer of the fallopian tube as a natural capsule without rupture. The surgery lasted for 43 min, and the volume of intraoperative blood loss was 5 mL. The pathology was confirmatory for interstitial pregnancy. The patient's beta-human chorionic gonadotropin levels decreased optimally. She had a normal postoperative course. This approach reduces intraoperative blood loss, minimizes myometrial loss and thermal injury, and effectively avoids persistent interstitial ectopic pregnancy. It is not limited by the device used, does not increase the surgery cost, and is greatly useful in treating a selected nonruptured distally or centrally implanted interstitial pregnancy.

RPLP1 Is Up-Regulated in Human Adenomyosis and Endometrial Adenocarcinoma Epithelial Cells and Is Essential for Cell Survival and Migration In Vitro.

Adenomyosis is defined as the development of endometrial epithelial glands and stroma within the myometrial layer of the uterus. These "ectopic" lesions share many cellular characteristics with endometriotic epithelial cells as well as endometrial adenocarcinoma cells, including enhanced proliferation, migration, invasion and progesterone resistance. We recently reported that the 60S acidic ribosomal protein P1, RPLP1, is up-regulated in endometriotic epithelial cells and lesion tissue where it plays a role in cell survival. To evaluate if a similar pattern of expression and function for RPLP1 exists in adenomyosis and endometrial cancer, we examined RPLP1 expression in adenomyosis and endometrial cancer tissue specimens and assessed its function in vitro using well-characterized cell lines. A total of 12 control endometrial biopsies and 20 eutopic endometrial and matched adenomyosis biopsies as well as 103 endometrial adenocarcinoma biopsies were evaluated for RPLP1 localization by immunohistochemistry. Endometrial adenocarcinoma cell lines, Ishikawa, HEC1A, HEC1B and AN3 were evaluated for RPLP1 protein and transcript expression, while in vitro function was evaluated by knocking down RPLP1 expression and assessing cell survival and migration. RPLP1 protein was up-regulated in eutopic epithelia as well as in adenomyosis lesions compared to eutopic endometria from control subjects. RPLP1 was also significantly up-regulated in endometrial adenocarcinoma tissue. Knockdown of RPLP1 in endometrial adenocarcinoma cell lines was associated with reduced cell survival and migration. RPLP1 expression is up-regulated in eutopic and ectopic adenomyotic epithelia as well as in the epithelia of endometrial cancer specimens. In vitro studies support an essential role for RPLP1 in mediating cell survival and migration, processes which are all involved in pathophysiology associated with both diseases.

Involvement of Oxytocin and Progesterone Receptor Expression in the Etiology of Canine Uterine Inertia

An altered oxytocin and progesterone receptor (OXTR and PGR, respectively) expression was postulated in canine uterine inertia (UI), which is the lack of functional myometrial contractions. OXTR and PGR expressions were compared in uterine tissue obtained during C-section due to primary UI (PUI; n = 12) and obstructive dystocia (OD, n = 8). In PUI, the influence of litter size was studied (small/normal/large litter: PUI-S/N/L: n = 5/4/3). Staining intensity in immunohistochemistry was scored for the longitudinal and circular myometrial layer and summarized per dog (IP-Myoscore). Mean P4 did not differ significantly between PUI (n = 9) and OD (n = 7). OXTR and PGR expressions (ratios) were significantly higher in PUI (OXTR: p = 0.0019; PGR: p = 0.0339), also for OXTR in PUI-N versus OD (p = 0.0034). A trend for a higher PGR IP-Myoscore was identified (PUI-N vs. OD, p = 0.0626) as well as an influence of litter size (lowest PGR-Myoscore in PUI-L, p = 0.0391). In conclusion, PUI was not related to higher P4, but potentially increased PGR availability compared to OD. It remains to be clarified whether OXTR is upregulated in PUI due to a counterregulatory mechanism to overcome myometrial quiescence or downregulated in OD due to physiological slow OXTR desensitization associated with an advanced duration of labor. Identified OXTR differences between myometrial layers indicate the need for further research.

Comparing the Effects of Consuming Propolis and Chicory for Eight Weeks and Resistance Training on Histopathological and Morphometric Changes of Uterine Tissue in Rats Treated With Testosterone Enanthate

Background: The illegal use of anabolic and androgenic steroids is a public health problem and their side effects in women are different from the side effects observed in men.
 Objectives: This study aims to compare the effects of consuming propolis and chicory for 8 weeks and resistance training on histopathological and morphometric changes of the uterine tissue in rats treated with testosterone enanthate.
 Methods: In this experimental study, 40 female Wistar rats were randomly divided into 5 groups (n=8): control (placebo), sham (resistance training), resistance training plus testosterone enanthate (20 mg/kg body weight), resistance training plus testosterone enanthate+chicory (6 g/kg body weight), and resistance training plus testosterone enanthate plus propolis (400 mg/kg body weight). The resistance training protocol was performed 5 sessions per week in 4 rounds with an intensity of 40% to 160% of the body weight of the mice for 8 weeks. After weighing and dissection, the uterine tissue was examined histologically.
 Results: The thickness of the endometrial layer in the sham, testosterone, and propolis groups showed a significant decrease compared to the control group (P<0.05). There was a significant decrease in the thickness of the functional layer in the sham, testosterone, chicory, and propolis groups compared to the control group (P<0.05). The thickness of the basal layer showed a significant decrease in the testosterone and propolis groups compared to the control group (P<0.05). Glands in the testosterone, chicory, and propolis groups showed a significant decrease compared to the control group (P<0.05). The thickness of the myometrial layer showed a significant decrease in the testosterone group compared to the control, sham, chicory, and propolis groups (P<0.05).
 Conclusion: The results showed that high-intensity resistance training combined with the use of testosterone enanthate causes histopathological changes in the uterus of female rats. Meanwhile, the use of propolis and chicory can improve the effects of testosterone enanthate as a treatment option.

Loss of the repressor REST affects progesterone receptor function and promotes uterine leiomyoma pathogenesis

Uterine leiomyomas (UL) are benign tumors that arise in the myometrial layer of the uterus. The standard treatment option for UL is hysterectomy, although hormonal therapies, such as selective progesterone receptor modulators, are often used as temporary treatment options to reduce symptoms or to slow the growth of tumors. However, since the pathogenesis of UL is poorly understood and most hormonal therapies are not based on UL-specific, divergent hormone signaling pathways, hallmarks that predict long-term efficacy and safety of pharmacotherapies remain largely undefined. In a previous study, we reported that aberrant expression of repressor element 1 silencing transcription factor/neuron-restrictive silencing factor (REST/NRSF) target genes activate UL growth due to the near ubiquitous loss of REST. Here, we show that ablation of the Rest gene in mouse uterus leads to UL phenotype and gene-expression patterns analogous to UL, including altered estrogen and progesterone signaling pathways. We demonstrate that many of the genes dysregulated in UL harbor cis-regulatory elements bound by REST and progesterone receptor (PGR) adjacent to each other. Crucially, we identify an interaction between REST and PGR in healthy myometrium and present a putative mechanism for the dysregulation of progesterone-responsive genes in UL ensuing in the loss of REST. Using three Rest conditional knockout mouse lines, we provide a comprehensive picture of the impact loss of REST has in UL pathogenesis and in altering the response of UL to steroid hormones.

A stepwise approach to robotic diffuse adenomyosis resection with double flap and concomitant abdominal cerclage

To propose a stepwise approach to robotic diffuse adenomyosis resection with double flap and concomitant abdominal cerclage. A narrated video footage of the surgical approach of a clinical case with extensive adenomyosis and recurrent abortions. Institutional review board approval was obtained (No 3.725.458). A university center. We present a case of a 37-year-old patient, gravida 4 para 0 with a history of 3 first trimester miscarriages after spontaneous pregnancies, and a 20-week spontaneous abortion after an invitro fertilization pregnancy. She underwent 2 laparoscopic excisions of deeply infiltrative endometriosis and was treated with gonadotropin-releasing hormone for 6 months and dienogest for a year with no improvement of her adenomyosis. Currently, she experiences moderate dysmenorrhea and desires future fertility. For 3 months, gonadotropin-releasing hormone analogues were used before performing the robotic surgery for adenomyosis resection and abdominal cerclage. (Step 1) Control the blood supply with a tourniquet placed lateral to the uterine arteries at the level of the internal cervical os, and a diluted solution of vasopressin 20% is administered at the area to be excised. (Step 2) Uterine incision: we use a vertical uterine incision with monopolar scissors, extended anteriorly and posteriorly. (Step 3) Resection of adenomyosis: carried with monopolar scissors using pure cut current. It is recommended that 0.5-1 cm of the myometrium is maintained around the uterine cavity as well as the serosa. (Step 4) Flap 1: interrupted sutures with vicryl 2.0 are used to approximate the inner myometrium close to the endometrial cavity, and a 2.0 barbed suture is used to approximate the inner myometrium of the contralateral side of the incision to the ipsilateral outer myometrium. (Step 5) Flap 2: another 2.0 barbed suture is used to approximate the outer myometrium of the contralateral side to the base of the repaired inner myometrial layer. (Step 6) Serosal closure: the serosa is approximated with a barbed suture in a baseball fashion before the tourniquet is released and hemostasis is ensured. (Step 7) Abdominal cerclage: a mersilene tape is placed medial to the uterine arteries at the level of the internal cervical os and a tape is tied anteriorly. Description of a stepwise approach to robotic diffuse adenomyosis resection with double flap and concomitant abdominal cerclage. The operating time was 255 min with minimal estimated blood loss (250ml). She was discharged with no complaints. Three months postoperatively, dysmenorrhea significantly improved, and the magnetic resonance imaging showed a good anatomic result. An embryo transfer is planned at 6 months postoperatively. A minimally invasive approach to fertility-sparing management of diffuse adenomyosis is safe and feasible with good anatomical results. However, it should be noted that after the removal of uterine adenomyosis, the patient should be advised on the high risk of uterine rupture during pregnancy. Robotic cerclage may also be performed concomitantly in cases of 2nd-trimester recurrent abortions.