查看更多>>摘要：Introduction: We aimed to investigate obstetric and neonatal outcomes and placental histological findings in in vitro fertilization (IVF) pregnancies complicated by gestational diabetes mellitus (GDM) as compared to unassisted pregnancies. Methods: This was a retrospective cohort of deliveries at a single university affiliated center between 12/2008 and 01/2020. Included were singleton pregnancies complicated by GDM, for which placental histopathological examination was performed. Obstetric, neonatal and placental outcomes were compared between pregnancies following IVF and unassisted pregnancies. Placental lesions were categorized according to the "Amsterdam" criteria. Results: Included were 688 deliveries with a diagnosis of GDM with placental examination - 69 IVF pregnancies (IVF group) and 619 unassisted pregnancies (control group). The IVF group was characterized by a significantly higher maternal age and higher rate of nulliparous women -60.8% vs. 32.9%, p < 0.001. There were no differences in GDM type between the study groups - about two thirds of cases were GDMA1 and on third GDMA2. A higher incidence of preeclampsia was noted in the IVF group - 17.3% vs. 9.3%, p = 0.03, with no difference in cesarean deliveries and birthweight. IVF deliveries were characterized by a significantly higher rate of adverse neonatal outcomes - 18.8% vs. 8.8%, p = 0.008, although this did not attain significance after adjustment to gestational age. No differences were noted in placental histology between the groups. Discussion: GDM in IVF is associated with a significantly higher rate of adverse neonatal outcomes, as compared with non-assisted pregnancies complicated by GDM. Placental histology does not shed light on these clinical associations.
Warrier, SudhaSundaram, S. MohanaVarier, LavanyaBalasubramanian, Ananthakrishnan...
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查看更多>>摘要：The emergence of COVID-19 has created a major health crisis across the globe. Invasion of SARS-CoV-2 into the lungs causes acute respiratory distress syndrome (ARDS) that result in the damage of lung alveolar epithelial cells. Currently, there is no standard treatment available to treat the disease and the resultant lung scarring is irreversible even after recovery. This has prompted researchers across the globe to focus on developing new therapeutics and vaccines for the treatment and prevention of COVID-19. Mesenchymal stem cells (MSCs) have emerged as an efficient drug screening platform and MSC-derived organoids has found applications in disease modeling and drug discovery. Perinatal tissue derived MSC based cell therapies have been explored in the treatment of various disease conditions including ARDS because of their enhanced regenerative and immunomodulatory properties. The multi-utility properties of MSCs have been described in this review wherein we discuss the potential use of MSC-derived lung organoids in screening of novel therapeutic compounds for COVID19 and also in disease modeling to better understand the pathogenesis of the disease. This article also summarizes the rationale behind the development of MSC-based cell- and cell-free therapies and vaccines for COVID-19 with a focus on the current progress in this area. With the pandemic raging, an important necessity is to develop novel treatment strategies which will not only alleviate the disease symptoms but also avoid any off-target effects which could further increase post infection sequelae. Naturally occurring mesenchymal stem cells could be the magic bullet which fulfil these criteria.
查看更多>>摘要：Introduction: Aquaporin 1 (AQP1) plays an important role in regulation of maternal-fetal fluid exchange and amniotic fluid volume. This present study aimed to determine the relationship between amniotic fluid index and placental AQP1 levels in terms of preeclampsia, and to reveal possible pathophysiological changes of AQP1 expression under preeclamptic conditions. Methods: Placental tissues and medical records information were obtained from 389 preeclamptic and 447 un-complicated pregnancies. Placental AQP1 levels were analyzed by molecular biological methods, DNA methyl-ation within gene promotor was determined by targeted bisulfite sequencing assay Results: Here, we found that preeclamptic pregnancy had a greater frequency of oligohydramnios, and higher placental AQP1 levels. There was a significantly inverse correlation between amniotic fluid index and placental AQP1 levels in preeclampsia cases. Additionally, the increased AQP1 was correlated with a decreased DNA methylation within its gene promoter. Discussion: Overall, this was the first description that a greater frequency of oligohydramnios in preeclampsia was strongly associated with reprogrammed AQP1 expression via a DNA methylation-mediated epigenetic mecha-nism. This study suggested AQP1 might play an important role in regulating maternal-fetal fluid balance under preeclamptic conditions, providing new information for further understanding the pathophysiological mecha-nism of oligohydramnios in preeclampsia.
查看更多>>摘要：Human embryo implantation is an intricate spatiotemporal process that involves the intimate association between the embryo and the endometrium of the mother. During implantation, the endometrium undergoes a dynamic cascade of gene activation and repression, largely driven by autocrine, paracrine, and endocrine action. Steroid hormones, such as estrogen and progesterone, act on a variety of targets including cellular adhesion molecules (CAMs), cytokines, and growth factors to facilitate the implantation process. Given the synchrony required to achieve implantation, it is unsurprising that embryo implantation represents a substantial problem for infertility patients. This is due to a complex interplay taking place at the level of the endometrium. This review discusses the intricacies of embryo implantation including the window of implantation, the cyclical phases of the endometrium, the implantation process itself, and features of endometrial receptivity. Additionally, we will discuss new research regarding inflammatory reproductive biology, epigenetics and microRNA, and the role of the vaginal and endometrial microbiome in implantation. A better understanding of embryo implantation and the interactions occurring at the level of the blastocyst and the endometrium will improve patient care for infertile patients who experience this frustrating challenge.
查看更多>>摘要：Introduction: Recent evidence supports the - rare - occurrence of vertical transplacental SARS-CoV-2 transmission. We previously determined that placental expression of angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 receptor, and associated viral cell entry regulators is upregulated by hypoxia. In the present study, we utilized a clinically relevant model of SARS-CoV-2-associated chronic histiocytic intervillositis/massive perivillous fibrin deposition (CHIV/MPFVD) to test the hypothesis that placental hypoxia may facilitate placental SARS-CoV-2 infection. Methods: We performed a comparative immunohistochemical and/or RNAscope in-situ hybridization analysis of carbonic anhydrase IX (CAIX, hypoxia marker), ACE2 and SARS-CoV-2 expression in free-floating versus fibrinencased chorionic villi in a 20-weeks' gestation placenta with SARS-CoV-2-associated CHIV/MPVFD. Results: The levels of CAIX and ACE2 immunoreactivity were significantly higher in trophoblastic cells of fibrinencased villi than in those of free-floating villi, consistent with hypoxia-induced ACE2 upregulation. SARS-CoV-2 showed a similar preferential localization to trophoblastic cells of fibrin-encased villi. Discussion: The localization of SARS-CoV-2 to hypoxic, fibrin-encased villi in this placenta with CHIV/MPVFD suggests placental infection and, therefore, transplacental SARS-CoV-2 transmission may be promoted by hypoxic conditions, mediated by ACE2 and similar hypoxia-sensitive viral cell entry mechanisms. Understanding of a causative link between placental hypoxia and SARS-CoV-2 transmittability may potentially lead to the development of alternative strategies for prevention of intrauterine COVID-19 transmission.
查看更多>>摘要：Introduction: Adverse pregnancy outcomes such as preterm delivery and preeclampsia are associated with a higher maternal risk for subsequent cardiovascular disease (CVD) and all-cause mortality. While such pregnancy conditions are related to abnormal placentation, little research has investigated whether pathologic placental measures could serve as a risk factor for future CVD mortality in mothers. Methods: Longitudinal study of 33,336 women from the Collaborative Perinatal Project (CPP; 1959-1966) linked to mortality information through December 2016. Pathologists took extensive morphological and histopathological measures. Apart from assessing associations with morphological features, we derived an overall composite score and specific inflammation-related, hemorrhage-related, and hypoxia-related pathologic placenta index scores. Cox regression estimated hazard ratios (HR) and 95% confidence intervals (CI) for mortality adjusting for covariates. Results: Thirty-nine percent of women died with mean (standard deviation, SD) time to death of 39 (12) years. Mean (SD) placental weight and birthweight were 436 g (98) and 3156 g (566), respectively. Placenta-tobirthweight ratio was associated with all-cause mortality (adjusted HR 1.03: 1.01, 1.05 per SD in ratio). In cause-specific analyses, it was significantly associated with respiratory (HR 1.06), dementia (HR: 1.10) and liver (HR 1.04) related deaths. CVD, cancer, diabetes and kidney related deaths also tended to increase, whereas infection related deaths did not (HR 0.94; 0.83, 1.06). Placental measures of thickness, diameters, and histopathological measures grouped by inflammatory, hemorrhagic, or hypoxic etiology were not associated with mortality. Discussion: Placental weight in relation to birthweight was associated with long-term maternal mortality but other histopathologic or morphologic features were not.
查看更多>>摘要：Introduction: Placental dysfunction triggers fetal growth restriction in congenital human cytomegalovirus (HCMV) infection. Studies suggest that HCMV infection interferes with the differentiation of human trophoblasts. However, the underlying mechanisms have not been clarified. This study investigated the impact of HCMV infection on gene transcriptomes in cytotrophoblasts (CTBs) associated with placental dysfunction. Methods: CTBs were isolated from human term placentas, and spontaneous syncytialization was observed in vitro. The transcriptome profiles were compared between CTB groups with and without HCMV infection by cap analysis gene expression sequencing. The effect of HCMV infection on trophoblast differentiation was evaluated by examining cell fusion status using immunocytochemical staining for desmoplakin and assessing the production of cell differentiation markers, including hCG, PlGF, and soluble Flt-1, using ELISA. Results: The expression of the genes categorized in the signaling pathways related to the cell cycle was significantly enhanced in CTBs with HCMV infection compared with uninfected CTBs. HCMV infection hindered the alteration of the gene expression profile associated with syncytialization. This suppressive effect under HCMV infection was concurrent with the reduction in hCG and PlGF secretion. Immunostaining for desmoplakin revealed that HCMV infection reduced the cell fusion of cultured CTBs. These findings imply that HCMV infection has a negative impact on syncytialization, which is indispensable for the maintenance of villous function. Discussion: HCMV infection interferes with gene expression profiles and functional differentiation of trophoblasts. Suppression of syncytialization may be a survival strategy for HCMV to expand infection and could be associated with placental dysfunction.
查看更多>>摘要：Introduction: Massive perivillous fibrin deposition (MPVFD) in the placenta is associated with pregnancy complications and maternal disease. The aim of the current study was to contribute with increased knowledge regarding MPVFD by comparing maternal characteristics, obstetric and perinatal outcome and recurrence rate according to the degree of MPVFD. Material and methods: This retrospective observational study included 141 cases of MPVFD collected between January 2003 to December 2018 in the Stockholm region, Sweden. The extent of fibrin deposition was assessed as low (20-32%), moderate (33-50%) or severe (>50%) according to macroscopic examination. Results: The study covered 48 placentas with low MPVFD, 41 with moderate and 52 with severe MPVFD. Severe MPVFD was associated with more prematurity than moderate and low MPVFDs (56.3% vs 34.2% and 34.0% respectively, p = 0.05 and p = 0.04). In cases with severe MPVFD, 72.3% of the liveborn infants were growth restricted compared to 34.2% in the moderate group (p = 0.001) and 52.2% in the low group (p = 0.06). The incidence of intrauterine fetal death was 31.3% in the severe MPVFD group, which was significantly higher than in the low MPVFD group (8.5%, p = 0.01) and twice as much as in cases with moderate MPVFD (15.8%, p = 0.07). 105 subsequent pregnancies after an index pregnancy with MPVFD were identified. The outcome was favourable with a liveborn rate of 91-100%. Discussion: The extent of fibrin in the placenta plays a role in pregnancy outcome. Cases with severe MPVFD in the placenta was associated with more prematurity, fetal growth restriction and intrauterine fetal death.
NSTL
Elsevier