Fetal Growth Restriction Placentas Research Articles

Placenta of Idiopathic Fetal Growth Restriction: Cytochemically Detectable Enzyme Activities do not Change at a Subcellular Level

The present study was designed to localize some important enzymes, such as adenosine diphospate-degrading enzyme (ADP-degrading enzyme) (plasma membrane enzyme), cytochrome c oxidase (mitochondrial enzyme) and glucose-6-phosphatase (endoplasmic reticulum enzyme), in placentae from patients with idiopathic fetal growth restriction (FGR) associated with absent end-diastolic flow velocity in the fetal umbilical artery. We compared these enzyme activities and their localization patterns to those in placentae both from pre-eclampsia with FGR and normal pregnancy with appropriate for their gestational age infants. In idiopathic FGR placentae, the intensity and localization patterns of these three enzymes did not differ from those seen in the placentae from normal pregnancy. Decreased ADP-degrading enzyme activity and cytochrome c oxidase negative mitochondria, which were characteristic features of pre-eclamptic trophoblasts, were absent from trophoblasts of the idiopathic FGR placentae. These observations indicated that enzyme-cytochemically detectable trophoblastic cell dysfunction may be absent in idiopathic FGR, or if present, there is less functional impairment of each trophoblast in this disease than in pre-eclampsia. Though both idiopathic FGR and pre-eclampsia lead to placental insufficiency, and finally to restricted fetal growth, a different mechanism and pathophysiology may work at the cellular and subcellular levels in these two diseases.

3 - Fetal Growth

Human idiopathic fetal growth restriction (FGR) is associated with placental insufficiency. Previously, we reported that the expression of homeobox gene Distal-less 3 (DLX3) is increased in idiopathic FGR placentae and is a regulator of villous trophoblast differentiation. Here, we identify the downstream targets of DLX3 in trophoblast-derived cell lines. We modelled the high levels of DLX3 in FGR using an over-expression plasmid construct and complemented this using short-interference RNA (siRNA) for inactivation in cultured cells. Using a real-time PCR-based gene profiling, candidate target genes of DLX3 over-expression and inactivation were identified as regulators of trophoblast differentiation; GATA2 and PPARγ. The expression of GATA2 and PPARγ were further assessed in placental tissues and showed increased mRNA and protein levels in FGR-affected tissues compared with gestation-matched controls. We conclude that DLX3 orchestrates the expression of multiple regulators of trophoblast differentiation and that expression of these regulatory genes is abnormal in FGR.