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-1α, HIF-2α and HIF-β (ARNT), along with prolyl hydroxylase domain 3 (PHD3), which leads to proteasomal degradation of HIF-α subunits. RESULTS: No statistically significant differences in the transcription levels of ARNT and HIF-2α were found between FGR and normal placentas. By contrast, PHD3 and HIF-1α 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.
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-1α, HIF-2α and HIF-β (ARNT), along with prolyl hydroxylase domain 3 (PHD3), which leads to proteasomal degradation of HIF-α subunits. RESULTS: No statistically significant differences in the transcription levels of ARNT and HIF-2α were found between FGR and normal placentas. By contrast, PHD3 and HIF-1α 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.
Authors: Sharon A McCracken; Sean K M Seeho; Tamara Carrodus; Jenny H Park; Narelle Woodland; Eileen D M Gallery; Jonathan M Morris; Anthony W Ashton Journal: Int J Mol Sci Date: 2022-03-02 Impact factor: 5.923