ESA-SRB-AOTA 2019

The effects of periconceptional ethanol exposure on markers of oxidative stress in maternal liver and late-gestation placental tissue (#693)

Sarah E Steane 1 , Tulika Das 1 , Jacinta I Kalisch-Smith 1 , Lisa K Akison 2 , Karen M Mortiz 2 , James SM Cuffe 1
  1. The University of Queensland, St Lucia, QLD, Australia
  2. Child Health Research Centre, The University of Queensland, St Lucia, QLD, Australia

Alcohol consumption during pregnancy can cause oxidative stress (OS) by impairing mitochondrial function in maternal and fetal tissues, potentially increasing the risk for chronic disease in offspring. The placenta is known to mediate fetal vulnerability to OS. However, it is unknown how alcohol impacts maternal and placental OS when exposure only occurs around conception. This study aimed to measure markers of OS in maternal and placental tissues following periconceptional alcohol exposure (PC:EtOH).

Sprague-Dawley dams were fed liquid diets containing 12.5% v/v EtOH (PC:EtOH) or 0% EtOH (control) from 4 days prior to mating until embryonic day (E)4. Maternal livers were collected at E5 and E20 and placentas at E15 and E20. Placentas were separated into junctional (JZ) and labyrinth (lab) zones and fetal sex determined. Mitochondrial content and markers of OS (Sod1/2, Cat, Gpx1/3, Txn1, Nos3/4) were measured using qPCR and 5 major oxidative phosphorylation (OXPHOS) protein complexes were measured by Western Blot. Hydrogen peroxide (H2O2) production and advanced glycation end-products (AGEs) were also measured.

Mitochondrial content was lower in maternal liver immediately following PC:EtOH at E5 (4-fold reduction compared to controls, P<0.0001), and remained low at E20 (P=0.011). Mitochondrial OXPHOS complexes were disrupted at E5 but there were no alterations in AGEs or H2O2 production. Although protein levels of some complexes were normalised by E20, ATP-synthase-complex levels decreased. In E15 placentas, there were no alterations in mitochondrial content following PC:EtOH exposure. However, there were placental zone- and sex-specific changes at E20 (reduced in female JZ, P=0.011). Sod1/2 and Txn1 were significantly elevated in JZ at E20 in PC:EtOH compared to controls.

PC:EtOH exposure directly alters the oxidative status of the maternal liver, with alterations persisting throughout pregnancy with impacts on placental development in a zone and sex-specific manner. This highlights differential placental adaptations to PC:EtOH regulate sex-specific fetal outcomes.