Endocrine Abstracts

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Normal placental and fetal growth are important for neonatal and lifelong health. Placental growth is influenced by endogenous microRNAs (miRs) which regulate translation of their target genes into proteins. Recently, plant miRs from ingested food have been detected in mammalian circulation; maternal fruit and vegetable intake is important for normal development but the underlying mechanisms are not well understood. We hypothesised that miRNAs from maternal dietary fruit and v...

Fetal growth restriction is associated with abnormal placental cell (cytotrophoblast) proliferation. Using an explant model of human first trimester placenta, we have demonstrated that the IGFI and -II stimulate proliferation in cytotrophoblast and are probably essential for normal placental growth. IGF activates signalling through both Akt and ERK, so the regulation of these pathways in placenta is important for normal pregnancy outcome. The tissue contains high levels of mic...

In humans, the exchange of nutrients and waste between mother and fetus occurs via the outer layer of the placenta (syncytium; ST); this layer is maintained by continuous growth and differentiation of underlying cytotrophoblasts (CT). Pregnancy complications such as intrauterine growth restriction are associated with abnormal CT proliferation and apoptosis; altered levels of maternal insulin-like growth factors (IGFs) have also been reported in these conditions. We have demons...

Pregnancy complications such as pre-eclampsia and intrauterine growth restriction are associated with abnormal placental cell (cytotrophoblast; CT) proliferation and apoptosis. The mechanisms regulating these events are unclear however altered levels of IGFs have also been reported in these conditions. Using an explant model of human first trimester placenta we have shown that both IGF-I and –II act through IGF1R mediated signalling pathways to enhance CT proliferation, d...

IGF-I and -II influence cytotrophoblast proliferation by activating the type-I IGF receptor (IGF1R) in first trimester human placenta. Ligand access to receptors is regulated by IGF binding proteins (IGFBPs) 1-6. In humans, the most abundant IGFBPs at the maternal-fetal interface are IGFBP-1 and IGFBP-3; we hypothesised that these IGFBPs function to regulate the effects of IGFs in the placenta and used our placental explant model, in which proliferation and differentiation are...

The insulin-like growth factors (IGFs) signal through the type 1 IGF receptor (IGFIR) to regulate cellular proliferation and survival. A current theory suggests that a subset of plasmalemmal lipid rafts, termed caveolae, may orchestrate such IGF-mediated signalling.In order to investigate the role of caveolae and the marker protein caveolin in controlling IGF signals, two cell models of caveolin deficiency were generated. Using shRNA, caveolin-1 expressi...

Conditions such as pre-eclampsia and intrauterine growth restriction highlight the importance of normal placental cell turnover for successful pregnancy outcome. In these conditions abnormal levels of proliferation and increased apoptosis have been reported; aberrations in components of the IGF axis have also been observed. IGFs regulate proliferation and survival in other cellular systems but their ability to influence human placental cell function remains to be established.<...

The insulin-like growth factors (IGFs) are important regulators of cellular function, with effects on growth, survival and metabolism mediated primarily through the type 1 IGF receptor (IGFIR). Recent work suggested that localisation of IGFIR to a subset of lipid rafts, known as caveolae, may be important for IGF function. In this study we have investigated whether these membrane domains were involved in IGF-I-mediated cell survival by comparing signalling in caveolae-positive...

Growth in utero depends on adequate development and function of the fetal / maternal interface. During pregnancy, the insulin-like growth factors (IGFs), which are known to be critically involved in placental development, are controlled by a binding protein - IGFBP-1 - produced by maternal decidualised endometrium. We have recently found that decidua also produces a protease which cleaves IGFBP-1 into fragments that are unable to bind ligand. This study aimed to identif...