Research Output per year
Fetal growth restriction (FGR) is characterized by the birth weight and body mass below the tenth percentile for gestational age. FGR is a major cause of perinatal morbidity and mortality and babies born with FGR are prone to develop cardiovascular diseases later in life. The underlying pathology of FGR is inadequate placental transfer of nutrients from mother to fetus, which can be caused by placental insufficiency. Hydrogen sulfide (H2S), a gaseous messenger is produced endogenously by cystathionine-lyase (Cth), cystathionine-β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST), which are present in human placenta. Recently, we demonstrated that the dysregulation of H2S/Cth pathway is associated with preeclampsia and blockade of CSE activity induces preeclampsia-like condition in pregnant mice. We hypothesized that defect in H2S pathways promote FGR and H2S donor restores fetal growth in mice where CBS or CSE activity has been compromised. Western blotting and qPCR revealed that placental CBS expressions were significantly reduced in women with FGR. ELISA analysis showed reduced placental growth factor production (PlGF) from first trimester (8–12 weeks gestation) human placental explants following inhibition of CBS activity by aminooxyacetic acid (AOA). Administration of AOA to pregnant mice had no effects on blood pressure, but caused fetal growth restriction. This was associated with reduced PlGF production. Histological analysis revealed a reduction in the placental junction zone, within which trophoblast giant cells and glycogen cells were less prominent in CBS inhibitor treated mice. These results imply that placental CBS is required for placental development and that dysregulation of CBS activity may contribute to the pathogenesis of FGR but not preeclampsia.
|Number of pages||2|
|Early online date||14 Apr 2015|
|Publication status||Published - 1 May 2015|
|Event||3rd European Conference on the Biology of Hydrogen Sulfide - Athens, Greece|
Duration: 3 May 2015 → 6 May 2015
Bibliographical noteAbstract from the 3rd European Conference on the Biology of Hydrogen Sulfide (H2S 2015), 3–6 May 2015, Athens, Greece.
Hydrogen sulphide rescues preeclampsia-like phenotype aggravated by high sFlt-1 in placenta growth factor (PlGF) deficiencyAhmad, S., Wang, K., Egginton, S., Hewett, P. W. & Ahmed, A., 1 May 2015, In : Nitric Oxide. 47, Suppl.1, p. S27-S28 2 p., PP36.
Research output: Contribution to journal › Conference abstract
Research output: Contribution to journal › Article