Activation of the arylhydrocarbon receptor through maternal beta-naphthoflavone exposure in the neonatal kidney.

Abstract

The kidneys of neonates are vulnerable to stressors due to their immature structure and function. Excess activation of the transcription factor arylhydrocarbon receptor (AhR) in the kidneys of neonates can cause severe hydronephrosis, as shown previously using 2,3,7,8-tetrachlorodibenzo-p-dioxin, an AhR agonist. In this study, we aimed to clarify the conditions under which AhR activation leads to hydronephrosis using beta-naphthoflavone (BNF), another potent agonist of AhR. Mouse dams were fed a BNF-containing diet, and the kidneys of their pups were examined. Maternal BNF exposure on postnatal day 1 (PND 1) significantly activated AhR, as evidenced by the increased mRNA levels of the target genes. However, AhR activation was hardly detectable on PND 2 or subsequent days although the mice were continually fed the BNF-containing diet. Further, no hydronephrosis or a related alteration was observed. Similarly, maternal BNF exposure from PND 6 induced significant AhR activation on PND 6 but not on PND 14. The overproduction of prostaglandin E₂ (PGE₂), which is a pivotal mechanism in the development of neonatal hydronephrosis, was not observed, and no hydronephrosis was observed. These results suggested that the intense activation of AhR on PND 1 or 6 is insufficient to induce overproduction of PGE₂ or hydronephrosis. Together with findings from previous studies, we conclude that the development of neonatal hydronephrosis depends on the duration and intensity of AhR activation.