Nisreen Kweider1, Berthold Huppertz2, Werner Rath3, Jessica Lambertz4, Rebecca Caspers5, Mohamed ElMoursi6,7, Ulrich Pecks5,8, Mamed Kadyrov1,9, Athanassios Fragoulis1, Thomas Pufe1, Christoph Jan Wruck1. 1. a Department of Anatomy and Cell Biology , RWTH Aachen University Hospital , Aachen , Germany. 2. b Institute of Cell Biology, Histology & Embryology, Medical University of Graz , Graz , Austria. 3. c Faculty of Medicine , Gynecology and Obstetrics, RWTH Aachen University Hospital , Aachen , Germany. 4. d Institut of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, RWTH Aachen University Hospital , Aachen , Germany. 5. e Department of Obstetrics and Gynecology , RWTH Aachen University Hospital , Aachen , Germany. 6. f Section of Obstetrics and Gynecology, Leeds Institute of Biomedical and Clinical sciences, University of Leeds , Leeds , UK. 7. g Department of Obstetrics and Gynecology , Mansoura University Faculty of Medicine , Mansoura , Egypt. 8. h Department of Obstetrics and Gynecology , University Hospital Schleswig-Holstein , Kiel , Germany , and. 9. i Department of Neurology Mittelbaden Klinikum Baden-Baden , Baden-Baden , Germany.
Abstract
OBJECTIVES: Intrauterine growth restriction (IUGR) is defined as a pathological decreased fetal growth. Oxidative stress has been connected to the restriction in the fetal growth. The transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) is a potent activator of the cellular antioxidant response. The effect Nrf2 on fetal-placental development has not yet been sufficiently investigated. Here, we evaluated the placental and fetal growth in Nrf2 knockout (Nrf2-KO) and Nrf2-wild type mice (Nrf2-WT) throughout pregnancy. METHODS: Heterozygote Nrf2 (Nrf2+/-) mice were paired to get Nrf2-KO and Nrf2-WT in the litters. Placentae and embryos from both genotypes were collected and weighed on days 13.5, 15.5 and 18.5 post coitum. The absolute volumes of the labyrinth zone and the total volume of the placenta were determined using the Cavalieri principle. RESULTS: On E 18.5 the fetal weight in Nrf2-KO was significantly reduced versus Nrf2-WT indicating a decrease in placental efficiency. A significant reduction in both total and labyrinth-volume in the placenta of Nrf2-KO mice was observed. CONCLUSION: This data points out the necessity of functional Nrf2 for fetal and placental growth. A deficiency in Nrf2 signaling may negatively affect nutrient transfer capacity which is then no longer able to meet fetal growth demands.
OBJECTIVES: Intrauterine growth restriction (IUGR) is defined as a pathological decreased fetal growth. Oxidative stress has been connected to the restriction in the fetal growth. The transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) is a potent activator of the cellular antioxidant response. The effect Nrf2 on fetal-placental development has not yet been sufficiently investigated. Here, we evaluated the placental and fetal growth in Nrf2 knockout (Nrf2-KO) and Nrf2-wild type mice (Nrf2-WT) throughout pregnancy. METHODS: Heterozygote Nrf2 (Nrf2+/-) mice were paired to get Nrf2-KO and Nrf2-WT in the litters. Placentae and embryos from both genotypes were collected and weighed on days 13.5, 15.5 and 18.5 post coitum. The absolute volumes of the labyrinth zone and the total volume of the placenta were determined using the Cavalieri principle. RESULTS: On E 18.5 the fetal weight in Nrf2-KO was significantly reduced versus Nrf2-WT indicating a decrease in placental efficiency. A significant reduction in both total and labyrinth-volume in the placenta of Nrf2-KO mice was observed. CONCLUSION: This data points out the necessity of functional Nrf2 for fetal and placental growth. A deficiency in Nrf2 signaling may negatively affect nutrient transfer capacity which is then no longer able to meet fetal growth demands.
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