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DOI: 10.1055/s-0040-1717943
Nrf2 Deficiency exaggerates inflammatory response in murine placenta
Introduction and Objectives increased oxidative stress has been demonstrated in pregnancies complicated by intrauterine growth restriction. The transcription factor Nrf2 is a master regulator of the cellular response to oxidative insults. The main objective of this study was to examine the effect of Nrf2-deletion on fetal and placental development in the knockout mouse model.
Materials and methods Placentas from Nrf2-knockout and Nrf2-wild type fetuses were collected during various stages of pregnancy. The total volume of each placenta was estimated using the Cavalieri estimator of volume. The other half was used for molecular biology analyses. Expression of the pro-inflammatory cytokines IL-6, IL-1, TNF-α and the anti-inflammatory enzyme Heme oxygenase-1 (HO- 1) were analyzed by ELISA. Immunostaining was performed to analyze the nuclear accumulation of the transcription factor NFΚB.
Results The Nrf2-deficient fetuses as well as their placentas presented significantly reduced weight when compared to the wild type ones. Placentas from preterm Nrf2-deleted fetuses showed significantly increased levels of the pro-inflammatory cytokines (IL-6 and TNF-α), and decreased expression of HO-1. The nuclear accumulation of the transcription factor NFΚB was significantly higher in Nrf2-deleted placentas.
Conclusion Our results show that the impairment in Nrf2 signaling is associated with a significant reduction in the fetal weight. The absence of Nrf2 intensifies NFΚB-activity, which in turn leads to increased cytokine production. These findings suggest that intrauterine inflammation may be a cause for the growth restriction in this model, and that the modulation of Nrf2 in response to NFΚB-activation reflects a protective mechanism against placental inflammation.
Publication History
Article published online:
07 October 2020
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