[125-POS]: Nrf2 deficiency interferes with trophoblast differentiation and affects the placental development in mice

A well-developed placenta is essential for a healthy pregnancy. A widespread oxidative stress and free radical damage and the resultant damage of the maternal endothelial cells have been implicated in preeclampsia. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a potent transcription activator that regulates the expression a group of antioxidants and detoxication enzymes. Recent discussion about a link between Nrf2 and vascular angiogenic balance in preeclampsia has focused on the downstream target protein, heme oxygenase-1 (HO-1). The effect Nrf2 on placental development has not been yet discussed. In particular, we evaluated the placental and fetal growth, the feto-placental phenotype and oxidative stress status in Nrf2 knockout (Nrf2-/-) mice at different stages of pregnancy.Placentae from Nrf2-/- and wild type Nrf2+/+ were collected on days 13.5, 15.5 and 18.5 post coitum. We performed H&E and Periodeic Acid Schiff on paraffin-embedded samples. Markers of oxidative stress, VEGF, Nrf2, 4-Hydroxynonenal (4-HNE) and HO-1 were assessed by immunohistochemical methods.At 18.5 days post coitum the fetal weight in Nrf2-/- was reduced (P<0.05) (0.8391±0.01569) versus Nrf2+/+ (0.9715±0.01897) indicating a decrease in placental efficiency. In the placentas of Nrf2-/- the labyrinth cells showed increased levels of the lipid peroxidation product 4-hydroxynonenal (4-HNE). Furthermore, in Nrf2-/--placentas there was a significant decrease in HO-1, an important endogenous antioxidant enzyme and a key regulator of trophoblast invasion and placental function. The labyrinth zones of these placentas were smaller when compared to Nrf2+/+-ones.Our results indicated that deficiency in Nrf2 signaling may reduce the placental functions, increase the levels of oxidative stress, which may negatively affect the nutrient transfer capacity to meet fetal growth demands.N. Kweider: None. J. Lambertz: None. T. Pufe: None. C.J. Wruck: None. W. Rath: None.