Search

STUDY QUESTION Can a functional in vitro model, containing the main cellular components of the uterine wall, be generated from cells derived from patient tissues? SUMMARY ANSWER We present a three-dimensional (3D) physiologically relevant, organ-on-a-chip model of the uterine wall containing primary endometrial and myometrial cellular participants, generated from human uterine tissue. WHAT IS KNOWN ALREADY As a highly dynamic reproductive organ, the human uterus plays fundamental physiological roles in menstruation and childbirth. The endometrial–myometrial junction (EMJ) defines the interface between the inner mucosal layer (endometrium) and outer smooth muscle zone (myometrium) that comprises the uterine wall. The EMJ is implicit in several uterine pathologies of unknown aetiology, including adenomyosis and abnormally invasive placenta; however, despite this, no patient-derived in vitro models of the uterine wall containing all EMJ participants currently exist. STUDY DESIGN, SIZE, DURATION We employed microfluidic technology to characterize multiple miniaturized models of the uterine wall. Protocols were tested that included variations in the seeding order of endometrial and myometrial fractions, and the addition of a low viscosity extracellular matrix to influence cell behaviour. Ultimately, functional hormone responses of patient-derived uterine wall models were assessed. PARTICIPANTS/MATERIALS, SETTING, METHODS Endometrial (n = 9) and myometrial biopsies (n = 4) were enzymatically dissociated to create epithelial, stromal and myometrial cellular fractions. Cell suspensions were seeded into non-adhesive poly(dimethylsiloxane) microfluidic devices containing 5 × 5 microwell arrays. The fate of individual cell types was monitored in real-time using fluorescent tracers, and cell phenotype was characterized by immunocytochemistry. Model functionality was assessed by measuring Ca2+ responses to agonist stimulation, and both insulin-like growth factor binding protein 1 (IGFBP-1) and osteopontin secretion in response to hormone stimulation. MAIN RESULTS AND THE ROLE OF CHANCE When subjected to microfluidic culture in isolation, endometrial stromal cells and smooth muscle myocytes formed compact spheroids, whilst epithelial cells produced diffuse aggregates. Tri-cultures were established by sequential seeding of individual or combined cell fractions at various ratios. Regardless of the protocol, epithelial cells localized to the outer periphery of tri-culture spheroids, which varied in morphology across the protocols. Incorporation of 5% [v/v] Matrigel® improved the reproducibility of 3D aggregates which exhibited robust self-assembly of a stromal/smooth muscle core encased in epithelium. Exposure of tri-cultures to oestradiol, medroxyprogesterone acetate and cyclic adenosine monophosphate (cAMP) increased secretion of IGFBP-1, which indicates stromal decidualization, and enhanced epithelial cell osteopontin secretion. Stimulation with endothelin-1 induced Ca2+ signalling in myocytes. LIMITATIONS, REASONS FOR CAUTION Endometrial and myometrial tissue was collected from relatively few donors. Myometrial tissue was collected from pregnant donors, which may have influenced the myocyte phenotype. Furthermore, endometrial tissue sampling was from women not having a hysterectomy, thus may not include the deeper basalis region, which may limit the physiological mimicry of the final models. WIDER IMPLICATIONS OF THE FINDINGS Our novel approach to modelling the uterine wall in 3D captures all of the main cell types in a medium-throughput system, enabling the screening of hundreds of cultures in parallel from a single biopsy. This system shows great promise for examining the cellular interplay between physiological cues and EMJ pathologies, such as the impact of uterine peristalsis and cyclical hormones on the pathogenesis of adenomyosis. STUDY FUNDING/COMPETING INTEREST(S) C.B. was supported by an Organ-on-a-Chip Technologies Network Pump Priming Project grant. C.J.H. was supported by a Wellbeing of Women project grant (RG2137), SRI/Bayer and Wellcome Trust IFFS3. D.K.H. was supported by a Wellbeing of Women project grant (RG2137) and MRC clinical research training fellowship (MR/V007238/1). M.Z. is Director and Co-Founder of ScreenIn3D Limited. The other authors declare no conflict of interest. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

This study was aimed to evaluated effects of smokeless tobacco on the uterine wall of female rats of Swiss albino species. This was a controlled experimental study with three groups of adult female Swiss albino rats. The study was conducted over a period of 31 days, at Animal House, Husbandry, and Veterinary Sciences at Sindh Agricultural University, Tandojam, and the Department of Anatomy, Isra University, Faculty of Medicine & Allied Medical Sciences, Hyderabad, Sindh, Pakistan. Thirty adult female Swiss albino rats were randomly assigned to three groups: Group A (control, no treatment), Group B (treated with 5% smokeless tobacco), and Group C (treated with 10% smokeless tobacco). Blood samples were collected on the 31st day to analyze Follicle-stimulating hormone (FSH) and Luteinizing hormone (LH) levels in the serum. After euthanization, uteruses were removed and weighed, followed by histological examination using Hematoxylin & Eosin and Mason's trichrome stains. The experimental groups (B and C) exhibited a significant reduction in uterine weight and decreased serum levels of FSH & LH. Histological examination showed cystically dilated submucosal glands and pronounced atrophy in the uteri of the experimental groups. Additionally, the myometrial wall thickness was also decreased. The use of smokeless tobacco negatively affects the uterine wall of female Swiss albino rats, resulting in histological changes and decreased serum levels of FSH and LH.

We studied the dynamics of morphological changes in the operated segment of the uterine horn of Sprague-Dawley rats during the first 2 weeks of the wound-healing process after a full-thickness surgical incision with regard to the estrous cycle phase. Morphometric parameters of injured uterine right horn were compared with those in the intact left horn of the same animal as a control of changes determined by the hormonal background. It was found that the uterine epithelium in the focus of injury was restored as soon as on day 2 after surgery under the influence of estrous cycle hormones. By day 4, the wound space was completely filled with the endometrial tissue on the side of the uterine lumen and coved by the attached adipose tissue of the mesentery on the side of the abdominal cavity. The thickness of the uterine wall and the uterine lumen differed most strongly between the operated and intact uterine horns during the first 3 days and on day 6 after surgery. The size of the healing area increased during the first three days and reached the peak value by day 3, but then decreased to minimum by day 6. [ABSTRACT FROM AUTHOR]

Objective: Lateral wall ruptures in women with a history of cesarean section are less common but more complicated than anterior wall ruptures. Residual myometrial thickness (RMT) is believed to be valuable for assessing the probability of ruptures. This study aimed to assess the utility of OmniView (a sonographic reslicing technique) in evaluating the lateral uterine wall after cesarean section and evaluate the relationship between lateral and anterior wall RMT using OmniView and sagittal two-dimensional ultrasound.Study Design: This cross-sectional study examined changes in both the anterior and lateral uterine wall in women with a history of cesarean section in the past 12-18 months. OmniView with volume contrast imaging with a 2-mm slice thickness was used to generate coronal planes, and the OmniView RMT (OV-RMT) was calculated as a percentage. Blinded to the OV-RMT results, sonographic multiplanar views were used to acquire the optimum sagittal plane for evaluating the RMT, and the sagittal RMT (S-RMT) was calculated as a percentage. The reproducibility of OV-RMT and S-RMT between two observers was tested using interclass correlation (ICC). The relationship between two variables was tested using Spearman's rank correlation.Results: In 208 recruited patients, the prevalence of lateral uterine wall defects was 79 %. The interobserver and intraobserver reproducibility of S-RMT and OV-RMT had ICC coefficients over 0.9 with a p-value <0.001. S-RMT and OV-RMT did not follow a normal distribution, and the medians were significantly different (55.5 and 85.7, respectively). Spearman's rank correlation between OV-RMT and S-RMT had a rho (ρ) value of 0.24 (p < 0.05). Passing-Bablok regression had an intercept of 47.95 and a slope of 0.65.Conclusion: OmniView can be used to assess lateral uterine wall defects, and OV-RMT is a reproducible and reliable method for quantifying this assessment. The RMT on the coronal plane was independently more intact than that on the sagittal plane, which might account for the lower incidence of lateral ruptures. Further studies could reveal a critical OV-RMT value that is safe for a trial of labor. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study is to utilize the niche measurement guidelines outlined by Jordans et al. in order to establish normal values and accurate description of caesarean section scars in a normal population. After defining the normal distribution, abnormal pregestational scar characteristics will be identified for predicting adverse pregnancy outcomes. Methods: This is a prospective observational multicenter clinical study where women with a history of only one caesarean section and yet open family planning are enrolled. The uterine length, cervical length, niche length, niche depth, niche width, residual myometrial thickness, endometrial thickness, scar to internal os distance, anterior myometrial thickness superior and inferior to the scar and the posterior myometrial thickness opposite the scar, superior and inferior to it are measured in a pregestational uterus. The lower uterine segment is measured over a length of 3 cm during subsequent pregnancy and followed up until delivery. Results: Data from 500 patients will yield normal distribution curves for all predefined measurements. Establishing a correlation between deviations from the normal measures and adverse events would be instrumental for counseling women regarding subsequent pregnancy and mode of delivery. Conclusion: This study will demonstrate the changes of the post‐caesarean scar from a non‐pregnant uterus until delivery and can confirm the importance of the scar characteristics in predicting pregnancy outcome. [ABSTRACT FROM AUTHOR]

Extra pelvic endometriosis, an underappreciated and misdiagnosed gynaecological problem has been reported here for its rare location. Patient presented with swelling and cyclical pain over vertical scar (caesarean). Diagnosis was made on high index of clinical suspicion which was complimented by Magnetic Resonance Imaging (MRI). Scar endometrioma extended from the skin upto the uterine serosa which is extremely rare. Wide excision of endometrioma followed by mesh repair was done. Histopathology confirmed the diagnosis.

Abstract: Purpose: To assess the role of ultrasound in the follow up of the progress of labor in terms of uterine wall thickness in its upper and lower segments. Methods: This is a prospective cross sectional study conducted in the period from March 2012 to August 2012. Included a total of 43 low risk pregnant women at Dallah hospital, Riyadh, Kingdom of Saudi Arabia. Trans-abdominal ultrasound was used to measure the uterine wall thickness. Results: With the progress of labor, the upper uterine wall progressively thickened, while the lower uterine segment progressively thinned. A significant change in uterine wall thickness was found with every 2cm cervical dilatation. A sono-partogram was developed. There was no significant difference in uterine wall thickness with respect to gravidity. The upper/lower uterine wall thickness ratio may also be valuable in the assessment of the progress of labor. We found that, measuring the uterine wall thickness by trans abdominal US is a non invasive method which has the potential role for assessing the progress of labor especially in high risk pregnancies when digital examination carries the risk of ascending infection or bleeding as in patients with preterm labor, premature rupture of membranes or ante-partum hemorrhage. Conclusions: Trans-abdominal US is a new non invasive method and has the potential for assessing the progress of labor. A sono-partogram is very useful in the follow up and evaluation of the progress of labor. [Copyright &y& Elsevier]

MIRD method with the Stabin/Segars anthropomorphic representations were used to calculate the absorbed doses in kidneys and uterine wall of an early-stage pregnant woman when 99mTc (DTPA), 99mTc (DMSA) and 99mTc (MAG3) are used for renal studies. Stabin and Segars anatomical representations are phantoms that are used in Monte Carlo calculations to determine the SAF, that with the pharmaceutical residence time are used to calculate the absorbed dose, from source organs, on target organs. Concerns about the impact on the absorbed dose due to the use of the three 99mTc-based compounds as well as the use of different phantoms were here treated for the case of a female at early pregnant state. The lowest absorbed dose in the kidneys was obtained with 99mTc (MAG3), and the relative difference of using Stabin and Segars anthropomorphic representations was 2.5%. For bladder and rest of organs the relative difference 14.63%. The lowest absorbed dose by uterine wall was obtained with 99mTc(DMSA), however the relative difference of using Stabin and Segars anthropomorphic representations was 12%. • DTPA, DMSA, and MAG3 compounds labeled with 99mTc are used for renal studies. • MIRD methodology is used to calculate the absorbed doses in kidneys and other organs. • The SAF for adult and child, male and female, phantoms (Stabin/Segars) are used in MIRD. • The absorbed doses due to 99mTc compounds in an early pregnant patient were calculated. • The impact on the absorbed dose of using Stabin or Segars representations was determined. [ABSTRACT FROM AUTHOR]