Zhang, YanpingLiu, MinLiao, LingyunWei, Xiaohong...
9页查看更多>>摘要：Introduction: Sirtuin 3 (SIRT3) plays a key role in many diseases by regulating cell necroptosis and biological behavior. However, the exact role of SIRT3 in preeclampsia remains unclear. Methods: The expression of SIRT3 and necroptosis biomarkers, including receptor-interacting protein kinase 1 (RIPK1), RIPK3 and phosphorylated mixed lineage kinase domain-like protein (p-MLKL), in the placentas of 20 healthy pregnancy controls and 20 preeclampsia patients was evaluated by immunofluorescence, quantitative real-time PCR and Western blot. The effect of hypoxia on trophoblast necroptosis was examined in HTR8/SVneo cells. The effects of SIRT3 on the necroptosis, invasion, migration, and tube formation of HTR8/SVneo cells were investigated by transfection with siRNA lentiviruses that silenced or overexpressed SIRT3. Results: The expression of SIRT3 was decreased and the expression of RIPK1, RIPK3 and p-MLKL was increased in placental trophoblasts from preeclampsia patients compared to those from healthy pregnancy controls. Hypoxia increased RIPK1, RIPK3 and p-MLKL expression in HTR8/SVneo cells, while necrostatin-1 pretreatment reduced RIPK1, RIPK3 and p-MLKL expression in HTR8/SVneo cells under hypoxia. SIRT3 silencing increased RIPK1, RIPK3 and p-MLKL expression and inhibited the invasion, migration, and tube formation of HTR8/SVneo cells under hypoxia. SIRT3 overexpression produced the opposite results. Discussion: We report that SIRT3 deficiency may be involved in the pathogenesis of preeclampsia by increasing necroptosis and causing abnormal trophoblastic biological behavior. The underlying mechanisms need further study.
原文链接:
NSTL
Elsevier
Liu, HanboNing, FenLash, Gendie E.
8页查看更多>>摘要：Uterine spiral artery remodeling is one of the key maternal adaptations of pregnancy, allowing delivery of the large volumes of maternal blood required for both placental and fetal growth. Failure of this process is associated with obstetric complications including preeclampsia, fetal growth restriction and miscarriage. Spiral artery remodeling is characterized by loss of the musculoelastic wall which is replaced by fibrinoid and intramural extravillous trophoblast cells (EVT). In recent years attention has focused on the initial stages of spiral artery remodeling which include separation of the vascular smooth muscle cells (VSMCs) and their phenotypic switch to a more synthetic phenotype, facilitating their migration away from the vessel wall. However, less is known about the final fate of the VSMCs. In vitro studies suggested that EVT could induce VSMC apoptosis, though VSMC apoptosis is not seen within the wall of the spiral arteries undergoing remodeling. However, apoptotic VSMCs have been observed amongst those cells which had migrated away from the vessel wall. This review article gives a brief overview of the current state of knowledge of the processes involved in spiral artery remodeling, and then concentrates on the mechanisms involved in VSMC apoptosis, drawing on knowledge from other vascular beds.
原文链接:- NSTL
- Elsevier
Dianat-Moghadam, HassanShadman, NasrinNouri, MohammadAlizadegan, Amin...
7页查看更多>>摘要：Various biopsy and sampling methods are used for preimplantation genetic diagnosis (PGD) of embryo. This method benefits blastomer/trophectoderm biopsy to improve the clinical outcome of in vitro fertilization (IVF). However, all of these procedures are invasive and have adverse effects on embryo development. Additionally, these procedures require expensive equipment and well-experienced technicians. Regarding these limitations, designing non-invasive methods is necessary. One of the recently proposed non-invasive and applicable methods is cell free DNA (cfDNA) molecule evaluation that have opened up exciting opportunities in the molecular diagnosis of embryo and fetus chromosomal aneuploidy. cfDNA is present in body fluids; especially blood, follicular fluid, amniotic fluid, spent embryo culture medium (SCM) and blastocoel fluid. Overall, this review highlights the cfDNA biomarker might constitute a supplemental tool for improving IVF and pregnancy outcomes, female infertility management. However, the successful application of cfDNA demands an understanding of its biological properties, kinetics, time of collection, high sensitivity and specificity cfDNA detection methods, and their limitation and challenges in the clinical settings. In this review we also describe ethical aspects of cfDNA testing.
原文链接:- NSTL
- Elsevier
Natenzon, AnnaMcFadden, PatrickDaSilva-Arnold, Sonia C.Zamudio, Stacy...
7页查看更多>>摘要：The mechanism by which human cytotrophoblast cells (CTB) differentiate into extravillous trophoblast cells (EVT) is an epithelial-mesenchymal transition (EMT). Polarized CTB, anchored in an epithelial layer, are transformed into motile, non-polar EVT which invade the uterus. Our previous research has shown that over gestation, invasive first trimester EVT are converted to a non-invasive phenotype showing a reduced degree of EMT. We hypothesized that in an under-invasion pathology, such as early onset preeclampsia, third trimester EVT would display a less advanced EMT profile than controls. The goal of this study was to determine whether expression of EMT-associated genes in the EVT of early onset preeclamptics shows a less mesenchymal, more epithelial phenotype compared to control pregnancies. Measures of preeclamptic CTB and EVT gene expression, using highly purified cells from third trimester, early onset preeclamptics and gestational-age matched controls, showed clear evidence of a phenotypic pattern characteristic of an EMT. Comparison of preeclamptic EVT to gestational-age matched, control EVT demonstrated multiple changes in gene expression, including changes in well-known EMT gene markers, indicative of a more limited EMT. These changes are not explained by differences in the preeclamptic CTB precursors. In this first study of purified third trimester EVT, we show that the pattern of gene expression corresponding to EMT-associated differentiation is diminished in early onset preeclampsia. This provides a mechanistic framework for many of the molecular changes observed in preeclampsia and presents an opportunity for detailed studies of the pathways regulating the aberrant EMT and for potential biomarkers of the process.
原文链接:- NSTL
- Elsevier
Chadha, RatiHorn, ChristopherWright, James R., Jr.Chan, Elaine S....
8页查看更多>>摘要：Introduction: Recurrence risk of villitis of unknown etiology (VUE) remains uncertain because of few studies and their methodologic limitations. We calculated recurrence risk in a large population of deliveries after minimizing important biases and compared it to others via systematic review and meta-analysis. Methods: Over 11 years of placenta pathology reports on singleton deliveries were retrieved and searched for 'villitis' or 'VUE'. Cases of acute villitis and chronic villitis from infections were eliminated via pathologist review. Reports were merged to data containing gestational age, parity and gravida. Recurrence risk of VUE per patient, per parity and per gravida was determined among patients with >= 2 placentas examined for deliveries >= 20 weeks gestation. Results were compared to those from articles and their references identified by a MEDLINE (R) search. Recurrence risks among methodologically similar studies were pooled using a random effects model. Results: Among 29 124 placenta pathology reports from 27 087 patients, there were 2423 cases of VUE among 2382 patients, of which 153 had >= 2 placentas examined. There were 41 recurrent cases of VUE for a recurrence risk of 27% per patient, 22% per parity, and 19% per gravida. We identified 64 articles, of which 4 were retained. One examined all placentas from all births over a similar to 3-year period, finding a recurrence risk of 27%. The remaining 3 studies, along with our own, used indications for placental examination and had a pooled recurrence risk of 30% (95% Confidence Interval: 0.21-0.41). Discussion: In our study, which is the largest, most comprehensive, and methodologically robust to date, VUE recurrence risk was similar to 30%.
原文链接:- NSTL
- Elsevier
Kingdom, JohnMelamed, NirAshwal, EranFerreira, Fabiana...
9页查看更多>>摘要：Introduction: Fetoplacental Doppler is considered to be a key tool for the diagnosis of placenta-mediated fetal growth restriction(FGR). We aimed to determine the diagnostic accuracy of fetoplacental Doppler for specific placental diseases. Methods: A retrospective cohort study of all women with a singleton pregnancy and an antenatal diagnosis of SGA fetus(estimated fetal weight <10th centile for gestational age), who underwent fetoplacental Doppler assessment within 2 weeks before birth. Primary exposure was any abnormal Doppler result, defined as an abnormal um-bilical artery(UA) Doppler, middle cerebral artery(MCA) Doppler, cerebroplacental-ratio(CPR), or umbilico-cerebral ratio(UCR). Study outcomes were abnormal placental pathology: maternal vascular malperfusion (MVM), villitis of unknown etiology(VUE), or fetal vascular malperfusion(FVM). Results: A total of 558 women with a singleton SGA fetus were included, of whom 239(42.8%) had an abnormal fetoplacental Doppler findings. UA Doppler had the lowest detection rate for abnormal placental pathology. MCA Doppler exhibited a significantly higher detection rate for all types of pathology. CPR and UCR exhibited highest detection rates for all types of placental pathology, however, were also associated with the highest false positive rate. The combination of fetoplacental Doppler with the severity of SGA and maternal hypertensive status achieved a high negative predictive value MVM lesions(97%). In contrast, fetoplacental Doppler did not improve the negative predictive value for non-MVM pathology(VUE or FVM). Discussion: Among SGA fetuses, the combination of UA and MCA Doppler is highly accurate in ruling out FGR due to MVM placental pathology, but is of limited value in excluding FGR due to underlying non-MVM pathologies.
原文链接:- NSTL
- Elsevier
Saif, ZarqaClifton, Vicki L.Meakin, Ashley S.Gough, Madeline...
10页查看更多>>摘要：Introduction: The mechanisms that contribute to continued male intrauterine growth in response to an adverse maternal environment, such as those brought on by maternal asthma, remain largely undefined but may, in part, be mediated by androgen-mediated signalling. We previously reported the expression of multiple AR protein isoforms in the human placenta and proposed the novel AR-45 isoform to be integral in mediating male-specific androgen-dependent signalling in the presence of maternal asthma. In the current study we have used an ex vivo approach to further understand sex-specific differences in placental androgen signalling in the presence and absence of inflammation using human term villous placental explants. Methods: Explants were cultured in the presence and absence of 0.1 nM dihydrotestosterone (DHT), 1 mu g/ml lipopolysaccharide (LPS), or DHT + LPS for 24hr. Tissue was used for gene expression and subcellular AR protein isoform expression. Results: Cytoplasmic and nuclear AR protein isoforms expression did not vary between culture conditions in either sex. AR-45 activity was upregulated in male placentae cultured in DHT, LPS and DHT + LPS only. There were no changes in the expression of androgen-mediated downstream targets in males in response to culture conditions, but females had significantly reduced IGF1R expression in response to LPS. Discussion: Increased AR-45 activity in the presence of inflammation may drive continued male feto-placental growth via maintained expression of downstream growth targets. Our findings build on previous work suggesting an important role for AR-45 in regulating male-specific adaptations to placental inflammation and underscores the need to further characterise the function of this AR isoform.
原文链接:- NSTL
- Elsevier
Brien, Marie-EveBouron-Dal Soglio, DorotheeDal Soglio, SolennCouture, Camille...
1页原文链接:- NSTL
- Elsevier
Nataly, FainsteinHadas, Ganer HermanOhad, GluckLetizia, Schreiber...
5页查看更多>>摘要：Introduction: The objective of the study was to investigate pregnancy outcome and placental pathology lesions among patients with gestational diabetes mellitus (GDM) versus patients with one abnormal value (OAV), in the oral glucose tolerance test (OGTT). Methods: A prospective study was performed from 2016 to 2019. All participants performed an OGTT between 24 and 28 weeks. Included patients who delivered at term (>37 weeks) with the diagnosis of GDMA2 (treated with insulin), GDMA1 (controlled with diet) and those with OAV. Maternal characteristics, pregnancy outcomes, and placental histopathology reports were compared between the GDMA2, GDMA1, and OAV groups. Placental lesions were classified according to "Amsterdam" criteria to maternal and fetal vascular malperfusion (MVM, FVM) lesions, and inflammatory lesions. Results: The GDMA2 group (n = 59) was characterized by higher maternal BMI (p < 0.001), increased rate of chronic hypertension (p < 0.01), cesarean delivery (CD) (p < 0.001), adverse neonatal outcomes (p < 0.001) and prolonged hospitalization (p < 0.001) as compared to the GDMA1 (n = 73) and the OAV group (n = 124). Average placental weight in the GDMA2 group were higher (p = 0.004). There were no between groups differences in the rate of placental MVM or inflammatory lesions. The OAV and GDMA1 groups were characterized by an increased rate of FVM lesions, as compared to the GDMA2 group (p = 0.02). Discussion: GDMA2 is associated with increased rate of CD and adverse neonatal outcome. The similar rate of placental MVM lesions among the study groups, and the increased rate of FVM lesions observed among the OAV group, implies of impaired placental function among the OAV group as in GDM pregnancies.
原文链接:- NSTL
- Elsevier
Graham, NicoleWallworth, RaianneKerby, AlanBatra, Gauri...
8页查看更多>>摘要：Histological examination of the placenta significantly contributes to diagnosis in adverse birth outcomes. One challenge in image analysis is variation in staining intensity caused by batch variation. We investigated if dynamic threshold image analysis methods may increase accuracy. Placenta samples were stained for endothelial cells and syncytial nuclear aggregates and analysed in Qupath software. Dynamically setting the threshold resulted in data more similar to manual method data. The method is simple and effective at modelling the dynamic interpretation of variation in staining intensity achieved by manual methods. We anticipate dynamic methods could be used to enhance placental diagnosis.
原文链接:- NSTL
- Elsevier
