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Expression of hypoxia-regulated genes and glycometabolic genes in placenta from patients with intrahepatic cholestasis of pregnancy

DOI: 10.1016/j.placenta.2014.06.372
  • Intrahepatic Cholestasis Of Pregnancy
  • Hypoxia
  • Oxidative Stress
  • Glucose Metabolism
  • Placenta
  • Biology
  • Chemistry


Abstract Introduction Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder unique to pregnancy that is associated with increased rates of fetal distress and demise. While acute hypoxia is believed to cause the pathophysiology of ICP, direct molecular evidence for this is lacking. Here, we analyzed expression of three hypoxia-regulated genes and several of their downstream target genes involved in glucose metabolism in placenta. Methods Placental tissue was collected from 20 women with normal pregnancies and 20 women with ICP. RNA and protein levels of hypoxia inducible transcription factors -1α (HIF-1α), development and DNA protein damage response 1 (REDD1), mammalian target of rapamycin (mTOR), glucose transporter type 1 (GLUT1), phosphoglycerate kinase1 (PGK1) and lacticdehydrogenase (LDHA) in placental tissue were measured by reverse transcriptase real time PCR and Western Blot. Proteins were also located by immunohistochemistry. Results Transcript levels were similar for all genes between the two types of placental tissue. In contrast, all protein levels except that of mTOR were significantly higher in placentas from ICP patients than the controls (P < 0.05). All proteins localized to the cytotrophoblast and syncytiotrophoblast. Discussion The placenta from ICP patients is more vulnerable to acute hypoxia and ischemia reperfusion injury. In response to hypoxia stress and oxidative damage in ICP, the placenta activates HIF-1α and REDD1, which in turn may up-regulates glucose transport and anaerobic glycolysis. Conclusions HIF-1α, REDD1 and mTOR may play a significant role in the reaction to hypoxia and oxidative stress and regulate glucose metabolism in the placenta of ICP patients.

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