PP021. The role of the transcription factor Nrf2 in the murine placental development

Pregnancy Hypertens. 2013 Apr;3(2):74-5. doi: 10.1016/j.preghy.2013.04.049. Epub 2013 Jun 6.

Abstract

Introduction: The placenta is the key organ for successful pregnancy and fetal growth. Oxidative stress during early human placental development is associated with pregnancy-related disorders. The transcription of many antioxidative-genes is mediated mainly through the transcription factor Nrf2. Furthermore, a link between Nrf2, vascular homeostasis and extravillous trophoblast invasion has been discussed.

Objectives: Here, we investigated the placental phenotype, placental and fetal weight of the Nrf2 knockout (Nrf2(-/-)) and wild type (Nrf2(+/+)) mice and the vascular function of these placentas around embryonic day 18.5.

Methods: We performed H&E, Periodic Acid Schiff (PAS) and immunohistochemistry of paraffin-embedded mouse placenta samples.

Results: There is no significant difference in both placental and fetal weight of both geno types (Nrf2(-/-) and Nrf2(+/+)). Phenotypic analysis of ED 18.5 placentas showed presence of trophoblast clusters in the labyrinth and frequent enlarged maternal blood lacunae. Furthermore, Nr2(-/-) showed increased levels in the lipid peroxidation product 4-hydroxinonoeal (4-HNE), which is a sensitive marker of oxidative damage and lipid peroxidation.

Conclusion: This data point out the necessity of a functional Nrf2 for placental development, as it may interact with the differentiation of the trophoblast lineage from one side and to diminish the oxidative damage during pregnancy from the other side.