Placental soluble fms-like tyrosine kinase expression in small for gestational age infants and risk for adverse outcomes

Spiel, Melissa; Salahuddin, Saira; Pernicone, Elizabeth; Zsengellér, Zsuzsanna K.; Wang, Alice; Modest, Anna M.; Karumanchi, S. Ananth

doi:10.1016/j.placenta.2017.02.011

Cited by 14 publications

(6 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[13][14][15][16] The soluble form of VEGFR-1, soluble fms-like tyrosine kinase 1 (sFlt-1), binds VEGF-A and PlGF, inhibiting their actions. In FGR and placental insufficiency, however, the normal balance of angiogenic factors is perturbed toward antiangiogenesis, with an increase in sFlt-1 and a reduction in the maternal circulating VEGF-A and PlGF observed in FGR and the related condition preeclampsia, [17][18][19][20][21] while PlGF is overexpressed in hypoxic ischemic placental lesions that are pathological hallmarks of FGR. 22 Therapies based on the manipulation of VEGF and related angiogenic factors are therefore likely to be effective for FGR.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Efficiency and Function of Vascular Endothelial Growth Factor Adenovirus Vectors in Endothelial Cells for Gene Therapy of Placental Insufficiency

et al. 2020

View full text Add to dashboard Cite

Severe fetal growth restriction (FGR) affects 1:500 pregnancies, is untreatable and causes serious neonatal morbidity and death. Reduced uterine blood flow (UBF) and lack of bioavailable VEGF due to placental insufficiency is a major cause. Transduction of uterine arteries in normal or FGR sheep and guinea pigs using an adenovirus (Ad) encoding VEGF isoforms A (Ad.VEGF-A 165 ) and a FLAG-tagged pre-processed short form D (D DNDC , Ad.VEGF-D DNDC -FLAG) increases endothelial nitric oxide expression, enhances relaxation and reduces constriction of the uterine arteries and their branches. UBF and angiogenesis are increased long term, improving fetal growth in utero. For clinical trial development we compared Ad.VEGF vector transduction efficiency and function in endothelial cells (ECs) derived from different species. We aimed to compare the transduction efficiency and function of the pre-clinical study Ad. constructs (Ad.VEGF-A 165 , Ad.VEGF-D DNDC -FLAG) with the intended clinical trial construct (Ad.VEGF-D DNDC ) where the FLAG tag is removed. We infected ECs from human umbilical vein, pregnant sheep uterine artery, pregnant guinea pig aorta and non-pregnant rabbit aorta, with increasing multiplicity of infection (MOI) for 24 or 48 hours of three Ad.VEGF vectors, compared to control Ad. containing the LacZ gene (Ad.LacZ). VEGF supernatant expression was analysed by ELISA. Functional assessment used tube formation assay and Erk-Akt phosphorylation by ELISA. VEGF expression was higher after Ad.VEGF-D DNDC -FLAG and Ad.VEGF-D DNDC transduction compared to Ad.VEGF-A 165 in all EC types (*p < 0.001). Tube formation was higher in ECs transduced with Ad.VEGF-D DNDC in all species compared to other constructs (***p < 0.001, *p < 0.05 with rabbit aortic ECs). Phospho-Erk and phospho-Akt assays displayed no differences between the three vector constructs, whose effect was, as in other experiments, higher than Ad.LacZ (***p < 0.001). In conclusion, we observed high transduction efficiency and functional effects of Ad.VEGF-D DNDC vector with comparability in major pathway activation to constructs used in pre-clinical studies, supporting its use in a clinical trial.

show abstract

Section: Introductionmentioning

confidence: 99%

Comparison of Efficiency and Function of Vascular Endothelial Growth Factor Adenovirus Vectors in Endothelial Cells for Gene Therapy of Placental Insufficiency

et al. 2020

View full text Add to dashboard Cite

show abstract

“…However, the exact pathogenesis of SGA remains unknown. A growing body of evidence suggests that SGA may be closely associated with impaired placental function, including placental vascular disease, pathogenic microbial infection, and abnormal changes in cytokine levels (Catov et al, 2008;Horgan et al, 2011;Lindner et al, 2013;den Hollander et al, 2017;Spiel et al, 2017). However, little is known about the immune microenvironment at the maternal-fetal interface of SGA infants.…”

Section: Discussionmentioning

confidence: 99%

The Maternal–Fetal Interface in Small-for-Gestational-Age Pregnancies Is Associated With a Reduced Quantity of Human Decidual NK Cells With Weaker Functional Ability

Lin

Yang

Feng

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Small for gestational age (SGA) refers to a birth weight that is less than the 10th percentile of the mean weight of infants at the same gestational age. This condition is associated with a variety of complications, and a high risk of cardiovascular and cerebrovascular diseases in adulthood. Decidual natural killer (dNK) cells at the maternal-fetal interface have received significant research attention in terms of normal pregnancy or miscarriage; however, data relating to SGA are limited. In this study, we aimed to investigate the characteristics and regulatory role of dNK cells at the maternal-fetal interface in SGA. Using immunofluorescence assays, we found that dNK cells maintained close contact with extra-villous trophoblasts, and the proportion of dNK cells in SGA decreased more than in appropriate for gestational age (AGA). Flow cytometry also showed that there was a significantly lower percentage of dNK cells in SGA (25.01 ± 2.43%) than in AGA (34.25 ± 2.30%) (p = 0.0103). The expression of the inhibitory receptor NKG2A on dNK cells and the secretion levels of both perforin and TGF-β1 from dNK cells were significantly higher in SGA than in AGA, while the cytotoxicity of dNK cells in SGA against K562 cells was attenuated. Compared to AGA, the functional ability of dNK cells in SGA showed significant functional impairment in promoting proliferation, migration, invasion, and tube formation in trophoblast cells or vascular endothelial cells. The abnormal function of dNK cells may affect fetal growth and development, and could therefore participate in the pathogenesis of SGA.

show abstract

“…SGA was defined as birthweight <10th percentile adjusted for gestational age and infant sex, using a US population as the norm 8 . In order to isolate infants who were more likely to be pathologically small, we conducted a secondary analysis using <3rd percentile as the definition of SGA 9,10 . All outcomes were assessed at the level of the pregnancy.…”

Section: Methodsmentioning

confidence: 99%

Multifoetal gestations mediate the effect of in vitro fertilisation (IVF) on ischaemic placental disease in autologous oocyte IVF more than donor oocyte IVF

Modest

Smith

Toth

et al. 2022

Paediatric Perinatal Epid

Self Cite

View full text Add to dashboard Cite

Background Ischaemic placental disease (IPD) affects 16%–23% of pregnancies in the United States. In vitro fertilisation (IVF) is a risk factor for IPD, and the magnitude of increase in risk differs for individuals using donor oocytes (donor IVF) versus their own oocytes (autologous IVF). In addition, multifoetal gestations, which are more common in IVF than non‐IVF pregnancies, also are a risk factor for IPD. Objective To quantify the contribution of multifoetal gestations to the association between IVF and IPD. Methods We conducted a retrospective cohort study at a tertiary hospital from 1 January, 2000 to 1 August 2018 using electronic medical records and state vital statistics data. IPD was defined as preeclampsia, placental abruption, small for gestational age (SGA) birth or an intrauterine foetal demise due to placental insufficiency. We used mediation analysis to decompose the total effect of IVF on IPD into a natural direct effect and an indirect effect through multifoetal gestations. We repeated the analyses separately for donor and autologous IVF. All models were adjusted for maternal age, race, parity, insurance, year of delivery and account for multiple pregnancies per person. Results We identified 86,514 deliveries, of which 281 resulted from donor IVF and 4173 resulted from autologous IVF. IVF pregnancies had 1.99 (95% CI 1.88, 2.10) times the risk of IPD compared to non‐IVF pregnancies, and 75.5% of this increased risk was mediated by multifoetal gestations. Autologous IVF pregnancies had 1.95 (95% CI 1.84, 2.07) times the risk of IPD compared to non‐IVF pregnancies, and the per cent mediated was 78.8%. Donor IVF pregnancies had 2.50 (95% CI 2.09, 2.92) times the risk of IPD, but the per cent mediated was 37.5%. Conclusion The majority of the association between autologous IVF and IPD was mediated through multifoetal gestations; however, this was not the case for donor IVF pregnancies.

show abstract

Placental soluble fms-like tyrosine kinase expression in small for gestational age infants and risk for adverse outcomes

Cited by 14 publications

References 38 publications

Comparison of Efficiency and Function of Vascular Endothelial Growth Factor Adenovirus Vectors in Endothelial Cells for Gene Therapy of Placental Insufficiency

Comparison of Efficiency and Function of Vascular Endothelial Growth Factor Adenovirus Vectors in Endothelial Cells for Gene Therapy of Placental Insufficiency

The Maternal–Fetal Interface in Small-for-Gestational-Age Pregnancies Is Associated With a Reduced Quantity of Human Decidual NK Cells With Weaker Functional Ability

Multifoetal gestations mediate the effect of in vitro fertilisation (IVF) on ischaemic placental disease in autologous oocyte IVF more than donor oocyte IVF

Contact Info

Product

Resources

About