Leucine-supplemented diet minimises tumour-induced damage in the placental tissue of pregnant tumour-bearing rats

Abstract

Cancer during pregnancy merges two complex metabolic and hormonal conditions, both poorly understood, which have the potential to exacerbate the condition of both the mother and the foetus. The branched chain amino acid leucine acts to improve cellular activity, especially by increasing protein synthesis. This study aims to analyse the modulatory effect of a leucine-rich diet on tumour-induced placental damage by evaluating the expression of genes involved in protein synthesis and degradation as well as the anti-oxidant enzymes activity in placenta tissue from pregnant tumour-bearing rats. Pregnant rats implanted with tumours or injected with ascitic fluid (the indirect effect of tumour growth) were subjected or not to leucine-rich diet. After 20 days of pregnancy, decreased placental protein synthesis and increased protein degradation were observed in the tumour-bearing and ascitic fluid-injected groups, especially in dams fed a normoprotein-diet, which resulted in low placental DNA content and high lipid peroxidation (malondialdehyde content). Placental protein synthesis gene expression was reduced in the tumour group, with increased expression of protein degradation and proteolytic subunit expression. A leucine-rich diet improved the placental cell signalling, ameliorating the DNA and protein content as well as the balance of placental protein synthesis and degradation activities, which could be reflected in improvements of in cell signalling, including the mTOR and eIFs pathway. The ascitic fluid injection mimicked the effects produced by tumour growth. In conclusion, the leucine-rich diet improved the placental metabolism and cell signalling, counteracting the damaging effects of the tumour. (AU)