Remodeling of uterine spiral arteries is critical for the continuation of a successful pregnancy. Uterine natural killer (uNK) cells are the predominant leukocyte population in the early pregnant decidua, and a role for these cells in spiral artery remodeling in pregnancy has been suggested. Angiogenic growth factors were measured in isolated uNK and total (unseparated) decidual cells (8-10 or 12-14 weeks gestation, n=5 each gestational age) after culture for 48 h. Angiopoietin (Ang)1, placental growth factor, transforming growth factor-beta1 (TGF-beta1), and vascular endothelial growth factor (VEGF)-C were measured by enzyme-linked immunosorbent assay. Angiogenin, Ang2, fibroblast growth factor basic, intercellular adhesion molecule (ICAM)-1, keratinocyte growth factor (KGF), platelet-derived growth factor-BB, and VEGF-A were measured using a FASTQuant angiogenic growth factor multiplex protein assay. Levels of Ang2, ICAM-1, and KGF, secreted by the total decidual fraction, decreased with increasing gestational age. uNK levels of Ang2 and VEGF-C also decreased with increasing gestational age. At 8-10 weeks gestation, there was no difference in the level of Ang1, Ang2, TGF-beta1, and VEGF-C secreted by uNK cells and the total decidual fraction. At 12-14 weeks, uNK cells secreted significantly lower levels of VEGF-C than the total decidual fraction. Early pregnancy decidua is a major source of angiogenic growth factors whose levels decrease with increasing gestational age, suggesting that they may play a role in spiral artery remodeling. uNK cells appear to be a prominent source of Ang1, Ang2, TGF-beta1, and VEGF-C within the placental bed.
BackgroundMedical students as future clinicians will apply their anatomy knowledge in medical imaging. There are various radiological resources available for the medical students to learn anatomy and contextualise it to the clinical setting. Ultrasound is a safe and non- invasive imaging procedure commonly used in clinical practice. This study aimed to use portable ultrasound and evaluate its impact as an adjunct to cadaveric anatomy teaching together with cross sectional anatomy images and line diagrams.MethodsUltrasound teaching was incorporated into upper limb and lower limb anatomy practical dissecting room sessions. The number of medical students who participated was 121 students from the year 2008 - 2009 and 94 students from the year 2009- 2010. The students were divided into groups of 15-20. Initially ultrasound demonstration was carried out on a volunteer and then the students were given the opportunity to use the ultrasound and identify normal anatomical structures visualized on images. For the students in the year 2009- 2010, ultrasound teaching was supplemented with cross sectional anatomy images and line diagrams. Questionnaires were distributed with seven questions rated using four point Likert scale and free text. Qualitative data was analysed using 2- proportion Z test and Fischer's exact test.ResultsThe number of students in the 2009-2010 year group who were confident in interpreting ultrasound images increased significantly when compared to the 2008-2009 year group of students. The majority of students were able to identify structures like bone, muscles and blood vessels on ultrasound images. There was a significant increase in the number of students who found the ultrasound teaching useful and also those who regarded ultrasound to have improved understanding of anatomy considerably.ConclusionsUltrasound acts as a useful adjunct to teach anatomy in a clinical context to medical students. The use of cross sectional anatomy images and line diagrams together can aid ultrasound image orientation of structures during these sessions. Early exposure to this imaging technology may prime students for later encounters with ultrasound during clinical practice.
Alterations in the balance of leucocyte populations in uterine decidua may lead to the generation of an unfavourable cytokine environment that is associated with unsuccessful pregnancy. Single and double immunohistochemical labelling was used to examine leucocyte populations in decidua from normal third trimester, foetal growth-restricted and pre-eclamptic pregnancies. Placental bed biopsies from 12 women undergoing elective Caesarean section with no hypertension or foetal growth restriction (FGR), 8 women with FGR without maternal hypertension and 12 women with pre-eclampsia (PE) were used to quantify decidual CD56C uterine NK cells, CD14C macrophages, CD3CT-lymphocytes and CD8C lymphocytes. CD3CCD56C, CD8CCD56C and CD161CCD3C double-labelled cells in decidua were compared in PE and control decidua. Decidual CD3CT-lymphocytes (P!0.01), CD8C cytotoxic T-lymphocytes (P!0.05), CD14C macrophages (P!0.0001) and CD56C uterine natural killer (uNK) cells (PZ0.01) were decreased in placental bed biopsies from women with PE compared with control third trimester decidua. By contrast, only CD56C uNK cells were decreased in FGR decidua (P!0.05). Double-positive CD8CCD56C cells were also decreased in PE compared with control third trimester decidua (P!0.05). The reduction in specific leucocyte subset numbers in PE and uNK cells in FGR suggests that altered local cytokine balance may be important in defective trophoblast invasion and spiral artery transformation in these pathological pregnancies.
Invasion of extravillous trophoblast cells into the uterus in human pregnancy is tightly regulated. The transforming growth factor-beta (TGFB) family has been suggested to play a role in controlling this process. We hypothesized that TGFB1, 2, and 3 would inhibit the invasive capacity of extravillous trophoblast cells. We also studied trophoblast apoptosis and proliferation and secreted protease levels as potential mechanisms by which these cytokines may act. Inhibition of endogenous TGFB1, 2, and 3 with neutralizing antibodies increased the invasive capacity of extravillous trophoblast cells derived from placental explants. Similarly, addition of exogenous TGFB1, 2, and 3 inhibited the invasive capacity of these cells in a dose-dependent manner. Proliferation of trophoblast in the placental explants did not alter in response to any of the cytokines tested. Apoptosis of villous and extravillous trophoblast did not alter in response to TGFB1, 2, and 3. There was a reduction in secreted levels of matrix metalloproteinase (MMP) 9 and urokinase plasminogen activator in response to all three cytokines. MMP2 and tissue inhibitor of metalloproteinase 1 and 3 levels were not altered. These results suggest that TGFB1, 2, and 3 inhibit trophoblast invasion by a mechanism dependent on reduced protease activity.
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