Quantitative 3D micro-CT imaging of the human feto-placental vasculature in intrauterine growth restriction.

OBJECTIVE: Placental vascular development matches fetal growth and development. Quantification of the feto-placental vasculature in placentas from pregnancies is complicated by intrauterine growth restriction (IUGR) revealed confounding results. Therefore, the feto-placental vascular volume in IUGR placentas was assessed by 3D micro-computed tomography (micro-CT). METHODS AND RESULTS: Placental probes from IUGR (n=24) and healthy control placentas (n=40) were perfused in situ with Microfil or BaSO(4) and randomly chosen samples were scanned by micro-CT. Using 3D images, we quantitated the feto-placental vascular volume fraction (VVF). A subanalysis was performed at three different levels, reaching from the chorionic plate artery (level A), to intermediate arteries (level B) and capillary system (level C). Results were complemented by histology. The significance of differences in vascular volume measurements was tested with analysis of variance [ANOVA]. RESULTS: Microfil perfused placentas showed a total vascular volume fraction of 20.5+/-0.9% in healthy controls. In contrast, the VVF decreased to 7.9+/-0.9% (p<0.001) in IUGR placentas. Significant differences were found between Microfil and BaSO(4) perfused placentas in the vascular volume fraction using micro-CT and histology. Micro-CT demonstrated localized concentric luminal encroachments in the intermediate arteries in placentas complicated by IUGR. CONCLUSION: Micro-CT imaging is feasible for quantitative analysis of the feto-placental vascular tree in healthy controls and pregnancies complicated by IUGR.

Analysis of the fetal placental vascular tree by X-ray micro-computed tomography.

The current understanding of the placental vascular tree largely derives from time-consuming morphometric analyses performed by conventional histology, electron microscopy of corrosion casts and three-dimensional reconstructions based on physical tissue sections. In the present study, we demonstrate for the first time that micro-computed tomography (micro-CT) emerges as a new, non-destructive and fast tool for imaging and quantifying fetoplacental vasculature. Term placentae (n=5) were perfused with contrast agent consisting of barium-sulfate, gelatine and thymol shortly after Caesarean-section-delivery. Samples (1 cm(3)) from eight different regions of the placenta were subsequently scanned in a micro-CT. Using tomographic reconstruction algorithms, three dimensional images were obtained by micro-CT allowing total stereoscopic visualization and continuous quantitative analysis of the vascular structure of the investigated samples. These samples were compared regarding vascular surface (VS) and vascular density (vascular volume fraction, TCVF). Quantitative assessment showed an average vascular density of 16 per cent (SD+/-0.4) and a vascular surface of 475 mm(2)(SD+/-8) per total tissue volume (including intervillous space) of 125 mm(3). Micro-CT image-analysis showed no significant differences in the fetal vascularization among term placentae. Micro-CT imaging is feasible for imaging and analysis of the villous vascular tree, allows further morphologic studies and immunohistochemistry of the placental specimens and may emerge as an additional tool in the investigation of the physiology and pathophysiology of the placental vasculature.

[Alternative treatment possibilities of complaints due to endometriosis]. / Alternative Behandlungsmöglichkeiten der endometriosebedingten Beschwerden.

Endometriosis is one of the main illnesses affecting women during their fertile age. Symptoms caused by endometriosis include dysmenorrhea, chronic pelvic pain, dyspareunia, menstrual disorders and infertility. Apart from surgical and medical treatment, including hormonal therapies, different alternative treatments exist. Ayurveda, homeopathy, dietary considerations as well as herbal therapies can be used as supplementary treatment for complaints caused by endometriosis. This article gives an overview over these alternative treatments, which many women experience as additionally useful.

[Expression of cell adhesion molecules in the extravillous trophoblast in placentas of preterm pregnancies and in placentas at term]. / Expression von Zelladhäsionsmolekülen im extravillösen Trophoblasten bei Plazenten von Frühgeburten und Plazenten am Termin.

Invasion of the human trophoblast is regulated by cell adhesion molecules (CAM) such as integrins and members of the immunoglobulin superfamily, which also play an important role in a number of immunological reactions. Abnormal trophoblast invasion of the uterus and its arterial system has been related to preterm delivery. We examined the differences of CAM expression in the extravillous trophoblast of preterm (n = 18) and term pregnancies (n = 21). Placenta and decidua frozen sections were examined by double-staining immunohistochemistry using antibodies against the immunoglobulin superfamily (ICAM-1, ICAM-2, ICAM-3, VCAM-1), integrins (alpha 2 beta 1, alpha 3 beta 1, alpha 4 beta 1, alpha 5 beta 1, alpha 6 beta 1) and cytokeratin. The percentage of immunopositive extravillous trophoblast cells and the intensity of immunoreactivity for the mentioned CAM antibodies was assessed. The expression of alpha 3 beta 1, alpha 5 beta 1 and VCAM-1 (p < 0.05) in the extravillous trophoblast of preterm placentas was lower than in normal placentas, whereas the expression of alpha 6 beta 1 in the extravillous trophoblast of preterm placentas was higher than at term (p < 0.05). No differences were observed for alpha 2 beta 1, alpha 4 beta 1, ICAM-1, ICAM-2 and ICAM-3. Our results show that there is a different expression of cell adhesion molecules in the extravillous trophoblast of placentas in preterm delivery. These differences in CAM might be associated with abnormal immunological and cell-cell interactions between mother and developing fetus and thus cause preterm labor and delivery.

Expression of cell adhesion molecules in the extravillous trophoblast is altered in IUGR.

PROBLEM: The invasion of trophoblast cells into the uterine wall and its arterial system is essential for the normal development of pregnancy. Cell adhesion molecules (CAM), such as the immunoglobulin superfamily and integrins, play a crucial role in a number of immunological reactions and in the invasion of the human trophoblast. Intrauterine growth restriction (IUGR) has been associated with abnormal trophoblast invasion. Therefore, the expression of CAM in the extravillous trophoblast of pregnancies complicated by IUGR might be different from normal pregnancies. METHOD OF STUDY: Normal (n = 21) and IUGR (n = 19) placentas were collected and stored at -70 degrees C. Immunohistochemistry (avidin-biotin complex peroxidase-doublestaining) of frozen tissue sections was performed using antibodies specific for the immunoglobulin superfamily vascular adhesion molecule-1 (VCAM-1; CD 106), intercellular adhesion molecule (ICAM-1) (CD 54), ICAM-2 (CD 102), ICAM-3 (CD 50), the integrins alpha 2 beta 1, alpha 3 beta 1, alpha 4 beta 1, alpha 5 beta 1, alpha 6 beta 1 and cytokeratin. The percentage of immunopositive extravillous trophoblast cells (EVT) and the intensity of the immunoreactivity for the various CAM and integrin antibodies was assessed. RESULTS: In IUGR placentas, there was less expression of VCAM-1 (CD 106), alpha 2 beta 1, alpha 3 beta 1, and alpha 5 beta 1 (P < 0.05) in the extravillous trophoblast than in normal pregnancies. Finally we observed for the first time that ICAM-3 was expressed on EVT and that its expression was markedly up-regulated in the EVT or IUGR placentas. No differences were found for ICAM-1 (CD 54), ICAM-2 (CD 102), alpha 4 beta 1 and alpha 6 beta 1. CONCLUSION: Our data show that there are significant differences in the expression of cell adhesion molecules of the extravillous trophoblast from IUGR and normal pregnancies. These differences might reflect changes in the immunological reactions and cell-cell interactions between mother and the developing fetus which could interfere with fetal growth.