Placental inflammation and oxidative stress in the mouse model of assisted reproduction

Abstract Higher rates of low birth weight and prematurity are observed in pregnancies generated with assisted reproduction technologies (ART). Both conditions have been associated with placental inflammation and oxidative stress. Since placental and fetal levels of progesterone, a major anti-inflammatory steroid, are decreased in murine ART, we investigated placental inflammation and oxidative stress in this model as potential mediators of negative birth outcomes. After generating mouse pregnancies by in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) we evaluated the antioxidant defense network and major inflammatory cytokines in maternal, placental and fetal tissues. Additionally, placentas were analyzed for total lipid levels, fibrosis, apoptosis, reactive oxygen species and integrity of intracellular nucleotides. Placentas from ART contained significantly less lipids, with greater levels of apoptosis and degraded nucleotides. Placentas from ICSI pregnancies had lower activities of superoxide dismutase (SOD), thioredoxin reductase (TrxR), xanthine oxidase (XO), catalase, glutathione-S-transferase (GST) glutathione peroxidase, and glutathione reductase (GR). Furthermore, GR, GST and SOD were also lower in fetal livers from ICSI pregnancies. Placentas from IVF pregnancies had decreased levels of SOD, TrxR and XO only. In placentas from both ICSI and IVF pregnancies IL-6 levels were significantly increased. These data suggest that ART is associated with placental inflammation (IL-6), oxidative stress and apoptosis but not fibrosis or remodeling. These effects are markedly greater with the ICSI technique. Since ICSI is ubiquitous, oxidative stress and placental inflammation associated with this method may be a critical factor in negative birth outcomes such as prematurity and low birth weight.