Abstract
Failure of the placental capillary network to develop normally is associated with early onset fetal growth restriction (FGR) and pre-eclampsia (PE). Although the symptoms are observed at term, the problem begins in the first trimester. However, investigations at this clinically relevant time are hindered by difficulties in identifying earlystage pregnancies that are at risk of developing FGR/PE. Using uterine artery Doppler ultrasound in the first trimester as a proxy measure of poor placentation, we have identified pregnancies at increased risk of developing early onset FGR/PE. Placental endothelial cells (PEC) isolated from pregnancies at increased risk of developing FGR/PE grew more slowly and their basal rate of apoptosis was significantly higher than that seen in the normal group. The pro-apoptotic stimulus, TNFα, induced apoptosis in cells from both groups but this was significantly greater in the high risk group. TNF receptor expression was unaffected. Inhibition of nitric oxide (NO) production significantly increased the sensitivity of cells from the normal pregnancies to TNFα but not in the high risk group establishing a functional role for NO in this system. In conclusion, first trimester PEC from pregnancies at increased risk of developing early onset FGR/PE were inherently more sensitive to apoptotic stimuli and this was functionally linked to the synthesis of NO. This may contribute to the poor placental vascular development seen in on going pregnancies.
Highlights
Fetal growth restriction (FGR) is a common pregnancy complication whereby the baby fails to reach its geneticallyThese authors contributed : Nicoletta Charolidi, Amanda J
Prior to developing an isolation protocol for first trimester Placental endothelial cells (PEC), we examined the expression of endothelial cell markers in placental tissue sections obtained from pregnancies
To mimic this we examined the sensitivity of PEC isolated from high-resistance index (high-RI) and normal-RI pregnancies to stimulation with TNFα in the presence of the mRNA synthesis inhibitor, actinomycin D
Summary
Fetal growth restriction (FGR) is a common pregnancy complication whereby the baby fails to reach its genetically. These authors contributed : Nicoletta Charolidi, Amanda J. It affects 5-8% of births worldwide and is a major cause of neonatal morbidity and mortality. Fetal weight correlates with placental weight and the placental weight of babies born with FGR is 24% less than that of an infant born with an appropriate weight for their age [1, 2]. It was once thought that poor placental development was purely a pregnancy related disorder, there is increasing evidence to support the idea that failure to thrive in utero, as a result of placental insufficiency, increases the risk of developing cardiovascular and metabolic diseases both in childhood and in later life [3]
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