Endocrine Abstracts

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 IGF-I and -II stimulate proliferation in cytotrophoblast and are probably essential for normal placental growth. IGF activates signalling through IGF1R/Akt/ ERK pathways, thus the ability of the placenta to modulate expression of components of these pathways is important for normal pregnancy...

Gestational Diabetes Mellitus (GDM) is associated with adverse outcomes, including large-for-gestational age (LGA) babies who are are at greater risk of developing cardiovascular and metabolic diseases in adulthood. The mechanisms responsible for LGA are unclear but it is associated with altered placental development/function. Recent data also shows a link between temporal changes in maternal glucose and LGA; women with GDM that deliver appropriate for gestational age (AGA) in...

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...

The IGF axis is imperative for normal placental development and function. In the human placenta, IGF1R regulates the actions of IGFs and consequently placental growth. Some microRNAs (miRs) are also known to regulate human placental growth. miR-145 is known to exert its effects on human placental growth by targeting IGF1R. Whilst the expression of some components within the IGF axis are similar between mice and humans, murine expression and function of IGF regulatory miRs has ...

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...

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...

Journal of Molecular Endocrinology, 2022, 68(2), 99-110 (DOI: https://doi.org/10.1530/JME-21-0175): ...

Aims: Women with gestational diabetes (GDM) who deliver large-for-gestational age (LGA) infants have subtle (1-1.5mM) differences in temporal maternal glucose control detectable by continuous glucose monitoring (CGM), compared to women who deliver appropriate-for-gestational-age (AGA) infants. It is unclear how these subtle changes cause LGA, but LGA has been linked to placental dysfunction. We aimed to develop an ex-vivo human placental model to mimic subtle differences in te...

Background: Gestational diabetes mellitus (GDM) is associated with increased rates of large-for-gestational-age (LGA) or small-for-gestational-age (SGA) infants. Currently, it is not possible to predict which women with GDM are at risk of delivering LGA or SGA infants. Fetuin-A, (α 2-Heremans Schmid glycoprotein; AHSG), a glycoprotein associated with insulin resistance is altered in GDM maternal serum. It is unclear if levels are related to altered fetal growth. This stud...