Increased uptake of dietary retinoids at the maternal-fetal barrier in the nitrofen model of congenital diaphragmatic hernia

Background/Purpose

The retinol signaling pathway is disrupted in congenital diaphragmatic hernia (CDH). Since there is no fetal retinol synthesis, maternal retinol has to cross the placenta. Nitrofen interferes with the retinol-binding protein (RBP) transfer pathway in CDH. However, in RBP knockout mice, retinol has been shown to be present. In this model, increased uptake of maternal dietary retinyl ester (RE) bounded in low-dense-lipoprotein (LDL) through low-density-lipoprotein-receptor 1 (LRP1) and increased activity of RE hydrolysis by lipoprotein-lipase (LPL) have been found. The aim of this study was to investigate the RE transfer pathway in the nitrofen CDH model.

Methods

Pregnant rats were treated with nitrofen or vehicle on gestational day (D9) and sacrificed on D21. Immunohistochemistry was performed to evaluate LRP1 and LPL protein expression. Serum LDL levels were measured by ELISA. Pulmonary and serum retinoid levels were measured using HPLC.

Results

Markedly increased trophoblastic and pulmonary LRP1 and LPL immunoreactivity were observed in CDH compared to controls. Significantly increased serum LDL and RE levels were observed in CDH compared to controls.

Conclusions

The increased uptake of dietary retinoids at the maternal-fetal barrier in the nitrofen CDH model suggests that the RE transfer pathway may be the main source of retinol in this model.