Mitochondrial gene expression profiles are associated with intrahepatic cholestasis of pregnancy

Maria Teresa Mella, Katherine Kohari, Richard Jones, Juan Peña, Lauren Ferrara, Joanne Stone, Luca Lambertini

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Introduction Intrahepatic cholestasis of pregnancy (ICP) affects 0.2–2% of pregnant women. While the maternal clinical course of ICP is usually benign, the fetal effects can be severe spanning from spontaneous preterm birth to fetal demise to long term effects on the health of the progeny. ICP is characterized by high maternal serum levels of bile acids and placental and hepatic bile acids accumulation. Intrahepatic cholestasis, in the non-pregnant state, has been also linked to alterations of the mitochondrial activity attributed to high oxidative stress rates driven by high intracellular bile acids concentrations. Here we explored the hypothesis that elevated bile acid levels of ICP modify the placental mitochondrial activity. Methods By using a set of 12 ICP and 12 control placenta samples, we assessed the expression of all 13 mitochondrial-encoded protein-coding genes and the mitochondrial DNA (mtDNA) relative abundance by real-time PCR. We also assessed the oxidative stress status by measuring DNA damage by ELISA. Results We determined that: 1) the expression of MT-ND4L (+53% – p < 0.01), MT-ND4 (−19%–0.05 < p ≤ 0.01), MT-ND5 (+40% – p < 0.01), MT-CYTB (+35% – p < 0.01) is associated with ICP; 2) the mtDNA relative abundance is not associated with ICP (0.098 in ICP vs 0.118 in controls – p > 0.05); 3) the oxidative stress status is associated with ICP (4403.9 pM 8-oxo-dG/μg DNA in ICP vs 3809.8 pM 8-oxo-dG/μg DNA in controls – p < 0.01). Discussion This preliminary study suggests that mitochondria in placenta respond to high oxidative stress to modify their gene expression which may play an important role in the pathophysiology of ICP.

Original languageEnglish
Pages (from-to)16-23
Number of pages8
JournalPlacenta
Volume45
DOIs
StatePublished - 1 Sep 2016

Keywords

  • Gene expression
  • Intrahepatic cholestasis of pregnancy
  • Mitochondria
  • Placenta

Fingerprint

Dive into the research topics of 'Mitochondrial gene expression profiles are associated with intrahepatic cholestasis of pregnancy'. Together they form a unique fingerprint.

Cite this