Kragsterman, EllenSinding, MarianneHansen, Ditte N.Peters, David A....
7页
查看更多>>摘要：Introduction: Specific placental pathologies that may impact fetal development, such as vascular malperfusion, are diagnosed postpartum. We aimed to evaluate if placental perfusion fraction (f) derived from intravoxel incoherent motion (IVIM) analysis of diffusion-weighted magnetic resonance imaging (DWI) can be used to identify specific types of placental vascular malperfusion antenatally. Method: 93 women who underwent placental DWI with multiple b-values at 23.9-41.3 week's gestation and postpartum histological examination were identified in the local placental MRI research database. Based on the placental examination, 44 were defined as normal controls and 49 cases had placental vascular malperfusion. Vascular malperfusion was subdivided into fetal vascular malperfusion (n = 13), maternal vascular malperfusion (n = 30) or both (n = 6). For each placenta, regions of interest were drawn on three placental slices and their mean f was estimated using intravoxel incoherence motion analysis. Results: In normal placentas mean f was 26.0 +/- 4.6% (mean +/- SD) and no linear correlation between f and gestational age was found, r = -0.05, p = 0.72. Placentas with fetal vascular malperfusion showed a significantly lower f (22.7 +/- 4.4%) compared to normal controls, p = 0.03. In cases of maternal vascular malperfusion (25.2 +/- 6.4%), no significant difference in f was revealed, p = 0.55. Conclusions: These results indicate that placental DWI-derived f may identify fetal vascular malperfusion in vivo. This study confirms a previous pilot study and provides initial evidence that fetal and maternal vascular malperfusion have different MRI signatures. Future studies are needed to further explore the clinical significance of this interesting finding.
查看更多>>摘要：Introduction: Placenta accreta spectrum (PAS) disorder is one of the major complications resulting in maternal death and serious adverse pregnancy outcomes. Uterine damage - principally that associated with cesarean section - is the leading risk factor for the development of PAS. However, the underlying pathogenesis of PAS related to uterine damage remains unclear. Methods: For this study, we constructed a mouse PAS model using hysterotomy to simulate a cesarean section in humans. Pregnant mice were sacrificed on embryonic days 12.5 (E12.5) and E17.5. Trophoblast invasion and placental vascularization were analyzed using Hematoxylin-Eosin (H&E) staining and immunohistochemistry (IHC), and the proportions of immune cells at the maternal-fetal interface were analyzed using flow cytometry. We analyzed the expressions of genes in the decidua and placenta using RNA sequencing and subsequent validation by QPCR, and measured serum angiogenic factors by ELISA. Results: Uterine damage led to increased trophoblast invasion and placental vascularization, with extensive changes to the immune-cell profiles at the maternal-fetal interface. The proportions of T and NK cells in the deciduas diminished significantly, with the decidual NK cells and M - 2 macrophages showing the greatest decline. The expression of TNF-alpha and IL4 was upregulated in the deciduas, while that of IFN-gamma and IL10 was downregulated significantly. The expression of Mmp2, Mmp9, Mmp3, and Dock4 was significantly elevated in the placenta, and the serum levels of anti-angiogenic factors were significantly attenuated. Discussion: Uterine damage can cause immune imbalance at the maternal-fetal interface, which may contribute to abnormal trophoblast invasion and enhanced vascularization of the mouse placenta.
查看更多>>摘要：Introduction: Intravoxel Incoherent Motion (IVIM) imaging has been used to assess placental microcirculatory flows. We proposed a joint analysis of flow-compensated (FC) and non-compensated (NC) diffusion MRI to estimate the fraction and velocity of ballistic microcirculatory flow (f(b) and v(b)), and evaluated the diagnostic performance of the new markers in maternal and fetal disorders. Methods: Gestational diabetes mellitus (GDM, n = 15) pregnancies and fetal growth restriction (FGR, n = 12), along with gestational age matched normal controls (n = 19 for GDM and 15 for FGR) underwent FC and NC-encoded IVIM scans at 1.5 T. f(b) and v(b) obtained from a FC-NC joint model, along with the conventional IVIM indices, were compared between patient groups for whole-placenta and maternal/fetal sides of the placenta. A linear support vector machine (SVM) was used to classify the GDM, FGR and controls. Results: v(b) of whole-placenta were significantly lower in both GDM (p = 0.017) and FGR (p = 0.043), compared with their controls, and the differences were more evident in the fetal side (p = 0.010 for GDM and p = 0.042 for FGR). f(b) and f(FC) showed group differences in the fetal side and D-FC showed differences in whole-placenta for GDM patients. In the classification task, v(b) showed the highest diagnostic accuracy of 70.6% for GDM and 63.0% for FGR, and the combination of f(b) and v(b) further improved the detection accuracy to 73.5% and 66.7% for GDM and FGR, respectively. Discussion: v(b) showed superior performance in the diagnosis of GDM and FGR, indicating the potential of the joint FC-NC IVIM method for placenta examinations.
查看更多>>摘要：Introduction: Proper placentation requires well controlled extravillous trophoblast cell (EVT) migration and invasion. Transforming growth factor beta (TGF beta) signaling has been well characterized as negatively regulating EVT migration and invasion. CLIC4 is an enhancer of TGF beta signaling, however CLIC4's function in placentation and its association to placental TGF beta signaling is unknown. Here we aimed to investigate the role of CLIC4 on trophoblast cell function and its relationship to TGF beta signaling. Methods: CLIC4 was immunolocalized in human placenta throughout gestation and the first trimester decidua. siRNA was used to knockdown CLIC4 in a human trophoblast cell line (HTR8/SVneo) to reveal functional consequences of CLIC4 loss on cell adhesion, proliferation, migration and invasion via xCELLigence. qPCR was used to identify downstream targets of CLIC4 in HTR8/SVNeo cells. Results: CLIC4 was widely expressed in the syncytiotrophoblast, cytotrophoblast and decidual cells across all trimesters of pregnancy with no significant difference in staining intensity in the different cellular compartments both across gestation and between compartments. Using immunofluorescent co-localization of CLIC4 and EVT marker HLA-G, we confirmed that CLIC4 localized to the cytoplasm of cell column EVTs in the first trimester decidua and nuclei of some EVTs that invaded in the decidua. Knockdown of CLIC4 in HTR8/SVneo cells significantly elevated cell adhesion, migration and invasion. Analysis of TGF beta signaling downstream targets identified that CDH2 and BAMBI expression were significantly increased after CLIC4 knockdown in HTR8/SVneo cells. Discussion: Our data support an inhibitory role for CLIC4 in regulating trophoblast migration and invasion, likely acting in part via BAMBI and CDH2.
查看更多>>摘要：Introduction: Preeclampsia (PE) is a pregnancy specific disorder which is significantly associated with maternal and neonatal morbidity and mortality. This study aimed to explore the potential role of circRNAs in PE. Methods: The mRNA, miRNA, and circRNA expression profiles of PE were downloaded from GEO database. Bioinformatics analysis was conducted to characterize differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs) and circRNAs (DEcircRNAs) in the placental tissues of women with PE versus normal pregnancies. Then, expression validation of the mRNAs, miRNAs and circRNAs were performed with RT-qPCR and GEO datasets. Results: A total of 1645 DEmRNAs, 41 DEmiRNAs and 2432 DEcircRNAs were acquired. The ceRNA network contained 4 circRNA-miRNA pairs and 64 miRNA-mRNA pairs, including 3 circRNAs, 3 miRNAs, and 63 mRNAs. Validation in RT-qPCR and GEO were generally in line with our integrated analysis results. Discussion: In conclusion, we speculated that hsa_circRNA_0001687/hsa-miR-532-3p/MMP14/AXL, hsa_circ_0001513/hsa-miR-188-5p/HMGCS1 and hsa_circ_0001513/hsa_circ_0001329/hsa-miR-760/MAP1LC3B axes may participate in the pathological process of PE.
查看更多>>摘要：Atypical protein kinase-c (aPKC) isoforms are important regulators of polarity and stem cell differentiation. There are three isoforms of aPKC: aPKC-iota, aPKC-zeta, and PKM-zeta. Recently, aPKC-iota was shown to regulate human trophoblast stem cell (TSC) differentiation. Compensation by remaining isoforms when a single aPKC isoform is lost can occur, but the expression pattern of aPKC-zeta in placenta is unknown. Here we show that aPKC-iota, aPKC-zeta and a new isoform, aPKC-zeta III, are expressed in trophoblasts. Therefore, studies examining the role of aPKC isoforms that control for potential compensation between aPKC isoforms are necessary to understand aPKCmediated regulation of TSC differentiation.
Galbally, MeganWatson, Stuart J.Spigset, OlavLappas, Martha...
8页
查看更多>>摘要：Introduction: Placental dysfunction and inefficiency, is important in understanding fetal growth restriction and low birth weight. Two recent studies have examined the relationship between antidepressant use in pregnancy and placental weight ratios; one found lower placental weight ratio associated with antidepressant use and the other found a higher ratio. Methods: This study examined 342 women recruited in early pregnancy, including 75 taking antidepressants, 29 with current depression and 238 controls. Antidepressant use was measured through self-report in early and late pregnancy, hospital records at delivery and drug concentrations in umbilical cord and maternal blood obtained at delivery. Maternal depression was measured using the Structured Clinical Interview for the DSM IV (SCID) at recruitment. Placentas were collected at delivery and weighed, and infant birth weight recorded. Placental efficiency was measured using standardised placental weight residuals and included as the outcome in general linear models (ANOVA/ANCOVA) to test hypotheses. Results: While placental weight was higher for those on antidepressants compared to controls (z=.30 c.f. Z=-0.08, p=.012), there were no significant differences between the three groups after adjusting for maternal body mass index at recruitment. When comparing antidepressant groups separately there were small-to-moderate positive associations between (SSRI) concentrations and placental weight (rho's > 0.20, p's > 0.05), which did not reach significance. Conclusion: Antidepressant use in pregnancy was not associated with significant changes in placental efficiency after adjustment for confounding variables. Future research should expand on this to examine other aspects of placental function and include a wide range of potential confounding variables to draw clinically meaningful conclusions.
Said, J. M.Wlodek, M. E.Briffa, J. F.Bevens, W....
11页
查看更多>>摘要：Introduction: Pre-eclampsia complicates 4.6% of pregnancies and is linked to impaired placentation; likely due to dysregulated vasculogenesis/angiogenesis. Proteoglycans, such as biglycan, are located on the endothelial surface of fetal capillaries. Biglycan is reduced in the placenta of pregnancies complicated by fetal growth restriction and pre-eclampsia. Importantly, biglycan stimulates angiogenesis in numerous tissues. Therefore, this study investigated whether biglycan knockdown in mice results in a pre-eclamptic phenotype. Methods: Wild-type (WT) and Bgn-/- mice underwent cardiorenal measurements prior to and during pregnancy. One cohort of mice underwent post-mortem on gestational day 18 (E18) and another cohort underwent postmortem on postnatal day 1 (PN1), with maternal and offspring tissues of relevance collected. Results: Bgn-/- dams had increased heart rate (+9%, p < 0.037) and reduced systolic (-11%, p < 0.001), diastolic (-15%, p < 0.001), and mean arterial (-12%, p < 0.001) pressures at all ages investigated compared to WT. Additionally, Bgn-/- dams had reduced urine flow rate (-64%, p < 0.001) as well as reduced urinary excretions (-49%, p < 0.004) during late gestation compared to WT. Bgn-/- pups had higher body weight (+8%, p = 0.004; E18 only) and a higher liver-to-brain weight ratio (+43%, p < 0.001). Placental weight was unaltered with only minor changes in vasculogenic and angiogenic gene abundances detected, which did not correlate to changes in protein expression. Discussion: This study demonstrated that total knockdown of biglycan is not associated with features of preeclampsia.
NSTL
Elsevier