Placental System A Amino Acid Transport is Reduced in Pregnancies With Small For Gestational Age (SGA) Infants but Not in Preeclampsia with SGA Infants

Shibata, Eiji; Hubel, Carl A.; Powers, Robert W.; Versen-Hoeynck, F. von; Gammill, Hilary S.; Rajakumar, Augustine; Roberts, James M.

doi:10.1016/j.placenta.2008.07.001

Cited by 55 publications

(60 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We propose that these mechanisms seen in other tissues may also be present in the placenta. Consistent with this, we have found that in placentas from SGA infants from mothers without PE in which adenosine receptors were not increased in our studies there was reduced uptake by system A amino acid transport in vitro [41]. However, in placentas from PE pregnancies with SGA infants in which adenosine receptors are increased, system A uptake was normal [41].…”

Section: Discussionsupporting

confidence: 87%

Human Placental Adenosine Receptor Expression is Elevated in Preeclampsia and Hypoxia Increases Expression of the A2A Receptor

Versen‐Höynck¹,

Rajakumar²,

Bainbridge³

et al. 2009

Placenta

Self Cite

View full text Add to dashboard Cite

Placental hypoxia as a result of impaired trophoblast invasion is suggested to be involved in the pathophysiology of preeclampsia. Hypoxia is a potent stimulus for the release of adenosine, and the actions of adenosine are mediated through four adenosine receptors, A 1 , A 2A , A 2B and A 3 . We investigated the presence, distribution and expression of adenosine receptor subtypes in the human placenta, the expression of the adenosine receptors in placentas from pregnancies complicated by preeclampsia, small for gestational age (SGA) infants and uncomplicated pregnancies, and the effect of hypoxia on placental adenosine receptor expression. Immunofluorescent microscopy localized A 1 , A 2A , A 2B and A 3 adenosine receptors to the syncytiotrophoblast, endothelial cells and myo-/ fibroblasts within the human placenta. Adenosine receptor protein and message expression levels were significantly higher in placentas from preeclamptic pregnancies with or without SGA infants, but not different in pregnancies with SGA infants alone. In vitro exposure of placental villous explants to hypoxia (2% oxygen) increased the expression of A 2A adenosine receptor 50%. These data indicate that all four known adenosine receptors are expressed in the human placenta and adenosine receptor expression is significantly higher in pregnancies complicated by preeclampsia. These data are consistent with the hypothesis that differences in placental adenosine receptors may contribute to alterations in placental function in preeclampsia.

show abstract

Section: Discussionsupporting

confidence: 87%

Human Placental Adenosine Receptor Expression is Elevated in Preeclampsia and Hypoxia Increases Expression of the A2A Receptor

Versen‐Höynck¹,

Rajakumar²,

Bainbridge³

et al. 2009

Placenta

Self Cite

View full text Add to dashboard Cite

show abstract

“…Conversely, FGR without pre-eclampsia occurs as a result of the absence of this signal. 38,40 We suggest that this model could be applied to the FGR cases of this study. Based on our results, it can be hypothesised that FGR babies with less severe disease produce a signal stimulated by the reduced placental nutrient and oxygen availability, in contrast to FGR babies with a more adverse outcome that fail to produce this signal.…”

Section: Discussionmentioning

confidence: 99%

Reduced placental prolyl hydroxylase 3 mRNA expression in pregnancies affected by fetal growth restriction

Gourvas

Sifakis

Dalpa

et al. 2010

BJOG

View full text Add to dashboard Cite

Objective To investigate the role of the hypoxia-inducible factor (HIF) pathway in fetal growth restriction (FGR).Design A case-control study.Setting Research laboratory and gynaecology clinic.Sample Twenty placentas from normal pregnancies and 20 from FGR pregnancies.Methods RNA extraction, cDNA synthesis, quantitative real-time polymerase chain reaction (qRT-PCR) assay, statistical analysis.Main outcome measures mRNA expression of HIF-1a, HIF-2a and HIF-b (ARNT), along with prolyl hydroxylase domain 3 (PHD3), which leads to proteasomal degradation of HIF-a subunits.Results No statistically significant differences in the transcription levels of ARNT and HIF-2a were found between FGR and normal placentas. By contrast, PHD3 and HIF-1a mRNA were downregulated in FGR placentas. PHD3 mRNA expression was associated with gestational age at delivery (P = 0.008), birthweight centile (P = 0.029) and abnormal umbilical artery (UA) Doppler measurements (P = 0.034).Conclusions As PHD3 regulates the HIF-mediated hypoxic response in FGR, we deduce that fetal adaptation to hypoxia ranges from impaired to adequate, as observed by the gradient of PHD3 downregulation in relation to the severity of FGR.

show abstract

“…Subsequently, the uptake of C 14 -MeAIB, a specific substrate transported by system A, was measured in sodium-containing and sodium-free (for non-specific uptake) Tyrodes buffer containing C 14 -MeAIB (1.7 μmol/L, 0.05μCi/ml) for 40 min at 37°C. Previous studies showed that the uptake of C 14 -MeAIB is linear up to 180 min [31, 32]. The uptake of C 14 -MeAIB by villous fragments was stopped by washing the fragments in ice-cold sodium-free Tyrodes buffer two times for 20 sec each.…”

Section: Methodsmentioning

confidence: 99%

Leptin Affects System A Amino Acid Transport Activity in the Human Placenta: Evidence for STAT3 Dependent Mechanisms

et al. 2009

Self Cite

View full text Add to dashboard Cite

Background: Amino acids are important nutrients during fetal development, and the activity of placental amino acid transporters is crucial in the regulation of fetal growth. Leptin, an adipocyte- and placenta-derived hormone, has been proposed to act as a peripheral signal in reproduction in humans. Leptin is elevated during pregnancy and elevated further in pathologic pregnancies such as preeclampsia. However, the role of leptin in placental function has not been fully elucidated. We hypothesize that leptin plays a role in the regulation of placental amino acid transport by activation of the JAK-STAT pathway. Methods: Placental amino acid transport, specifically system A transport was studied in placental villous fragments using the amino acid analog, methylaminoisobutyric acid (MeAIB). Specific inhibitors of the JAK-STAT signal transduction pathway were used to further elucidate their role in leptin-mediated effects on amino acid transport activity. Western blotting was performed to identify STAT3 phosphorylation as a measure of leptin receptor activation. Results: Leptin significantly increased system A amino acid transporter activity by 22-42% after 1 h of incubation. Leptin activated JAK-STAT signaling pathway as evidenced by STAT3 phosphorylation, and inhibition of STAT3 or JAK2 resulted in 36-45% reduction in system A amino acid transporter activity. Furthermore, blocking endogenously produced leptin also decreased system A transport by 45% comparable to STAT3 inhibition. Conclusions: These data demonstrate that leptin stimulates system A by JAK-STAT dependent pathway in placental villous fragments. Our findings support the autocrine/paracrine role of leptin in regulating amino acid transport in the human placenta.

show abstract

Placental System A Amino Acid Transport is Reduced in Pregnancies With Small For Gestational Age (SGA) Infants but Not in Preeclampsia with SGA Infants

Cited by 55 publications

References 23 publications

Human Placental Adenosine Receptor Expression is Elevated in Preeclampsia and Hypoxia Increases Expression of the A2A Receptor

Human Placental Adenosine Receptor Expression is Elevated in Preeclampsia and Hypoxia Increases Expression of the A2A Receptor

Reduced placental prolyl hydroxylase 3 mRNA expression in pregnancies affected by fetal growth restriction

Leptin Affects System A Amino Acid Transport Activity in the Human Placenta: Evidence for STAT3 Dependent Mechanisms

Contact Info

Product

Resources

About