Reduced placental prolyl hydroxylase 3 mRNA expression in pregnancies affected by fetal growth restriction

Abstract

Objective To investigate the role of the hypoxia-inducible factor (HIF) pathway in fetal growth restriction (FGR).Design A case-control study.Setting Research laboratory and gynaecology clinic.Sample Twenty placentas from normal pregnancies and 20 from FGR pregnancies.Methods RNA extraction, cDNA synthesis, quantitative real-time polymerase chain reaction (qRT-PCR) assay, statistical analysis.Main outcome measures mRNA expression of HIF-1a, HIF-2a and HIF-b (ARNT), along with prolyl hydroxylase domain 3 (PHD3), which leads to proteasomal degradation of HIF-a subunits.Results No statistically significant differences in the transcription levels of ARNT and HIF-2a were found between FGR and normal placentas. By contrast, PHD3 and HIF-1a mRNA were downregulated in FGR placentas. PHD3 mRNA expression was associated with gestational age at delivery (P = 0.008), birthweight centile (P = 0.029) and abnormal umbilical artery (UA) Doppler measurements (P = 0.034).Conclusions As PHD3 regulates the HIF-mediated hypoxic response in FGR, we deduce that fetal adaptation to hypoxia ranges from impaired to adequate, as observed by the gradient of PHD3 downregulation in relation to the severity of FGR.

Downregulation of Notch Signaling Pathway in Late Preterm and Term Placentas from Pregnancies Complicated by Preeclampsia

“…Statistical analysis revealed that PE-affected pregnancies with BWC<5 had increased DLL3 mRNA and NICD3 protein levels compared with PE-affected pregnancies with BWC>5. This observation is similar to one in our previous study on pregnancies complicated by FGR, in which PHD3 , a member of the HIF hypoxia pathway, was higher in babies born from FGR pregnancies with BWC<0.5 compared to babies born from FGR pregnancies with BWC>0.5 [ 19 ]. Additionally, in women with PE that were on their first parity, HEY2 transcript levels were increased compared with PE women that gave birth to their 2 nd or 3 rd child.…”

Partial depletion of yolk during zebrafish embryogenesis changes the dynamics of methionine cycle and metabolic genes

“…The observed down-regulation in YD embryos of egln2 and egln3 (regulators of hypoxia-inducible factors (Hifs) [ 23 ] and also known as phd1 and phd3 [ 24 ]) at 32 hpf and 24/48 hpf respectively, complies with hypoxia signaling in YD embryos ( egln3 has been validated by qRT PCR, Additional file 6 , see Additional file 2 for DE values). Egln3 down-regulation in YD embryos is reminiscent with down-regulation of its human orthologue in placenta from fetal growth restricted (FGR) children [ 25 ]. Hypoxia signaling has also been observed in fetal murine hearts and brains from undernourished mothers [ 26 , 27 ] and is consistent with pronounced oxidative stress in small-for-gestational age (SGA) newborns from undernourished mothers [ 9 ].…”

Placental mRNA expression of angiopoietins (Ang)-1, Ang-2 and their receptor Tie-2 is altered in pregnancies complicated by preeclampsia

“…Total RNA was extracted using TRIzol as described previously [36,37]. Placental tissues were cut into small sections and homogenized in the presence of 1 ml TRIzol.…”