Impact of leucine-rich diet on placenta's proteomic and metabolomic profiles of pregnant tumor-bearing rats.

Abstract

Cancer during pregnancy is a fragile scenario where the maternal body undergoes significant molecular changes, including at proteomic and metabolomic levels, with damage to placenta and fetal development. Proteomic and metabolomic interaction analyses can clarify the complex dynamics in cancer associated with pregnancy. Leucine is involved in protein synthesis and metabolic regulation and may attenuate tumor-induced damage. We investigated placental proteomic and metabolomic profiles in the complex relationships among pregnancy, cancer, and leucine supplementation. Exploratory, non-targeted proteomic (mass spectrometry) and metabolomic (NMR spectrometry) analyses were performed on the placenta tissue of four pregnant groups: control (PC), Walker-256 tumor-bearing (PW), leucine (PL), and tumor-bearing fed a leucine-rich diet (PWL). Statistical comparisons were performed on technical replicate data within each group. Tumor affected maternal weight, but leucine attenuated the decrease in placental weight and fetal resorption. Leucine supplementation restored the placental proteins involved in the nuclear structure, cytoskeleton, and immune response. Tumor evolution impaired pathways related to protein folding and chromosome localization, whereas leucine modulated interferon-gamma and hydrogen peroxide responses. PW placentas exhibited decreased adenosine, glucose, glutamate, and succinate, with enhanced lactate, creatine, and histamine levels, whereas leucine supplementation restored adenosine and pyridoxine and reduced lactate levels. The affected alanine/aspartate/glutamate and purine metabolism, beta-alanine metabolism, and the citrate cycle were minimized in leucine treatment (PWL), which mainly modulates purine and alanine/aspartate/glutamate pathways and pyruvate metabolism. A leucine-rich diet partially restored placental protein and metabolite levels, leading affected pathways to shift towards amino acid biosynthesis and pyruvate metabolism and minimizing effects on fetal development.