Abstract
BackgroundThe occurrence of cancer during pregnancy merges two complex, poorly understood metabolic and hormonal conditions. This association can exacerbate the conditions of both the mother and the foetus. The branched-chain amino acid leucine enhances cellular activity, particularly by increasing protein synthesis. This study aimed to analyse the modulatory effect of a leucine-rich diet on direct and indirect tumour-induced placental damage. This was accomplished by evaluating the expression of genes involved in protein synthesis and degradation and assessing anti-oxidant enzyme activity in placental tissues collected from pregnant, tumour-bearing rats.ResultsPregnant rats were either implanted with Walker 256 tumour cells or injected with ascitic fluid (to study the indirect effects of tumour growth) and then fed a leucine-rich diet. Animals in a control group underwent the same procedures but were fed a normal diet. On the 20th day of pregnancy, tumour growth was observed. Dams fed a normoprotein diet showed the greatest tumour growth. Injection with ascitic fluid mimicked the effects of tumour growth. Decreased placental protein synthesis and increased protein degradation were observed in both the tumour-bearing and the ascitic fluid-injected groups that were fed a normoprotein diet. These effects resulted in low placental DNA and protein content and high lipid peroxidation (measured by malondialdehyde content). Decreased placental protein synthesis-related gene expression was observed in the tumour group concomitant with increased expression of genes encoding protein degradation-associated proteins and proteolytic subunits.ConclusionsConsumption of a leucine-rich diet counteracted the effects produced by tumour growth and injection with ascitic fluid. The diet enhanced cell signalling, ameliorated deficiencies in DNA and protein content, and balanced protein synthesis and degradation processes in the placenta. The improvements in cell signalling included changes in the mTOR/eIF pathway. In conclusion, consumption of a leucine-rich diet improved placental metabolism and cell signalling in tumour-bearing rats, and these changes reduced the deleterious effects caused by tumour growth.
Highlights
The occurrence of cancer during pregnancy merges two complex, poorly understood metabolic and hormonal conditions
We demonstrated that consumption of a leucine-rich diet enhances protein synthesis in muscle
In the current study, we demonstrated that dietary leucine supplementation enhances placental cell signalling, ameliorates deleterious alterations in DNA and protein content, and increases placental cell number
Summary
The occurrence of cancer during pregnancy merges two complex, poorly understood metabolic and hormonal conditions This association can exacerbate the conditions of both the mother and the foetus. This study aimed to analyse the modulatory effect of a leucine-rich diet on direct and indirect tumour-induced placental damage This was accomplished by evaluating the expression of genes involved in protein synthesis and degradation and assessing anti-oxidant enzyme activity in placental tissues collected from pregnant, tumour-bearing rats. Neoplasias are difficult to control and treat because they are associated with several biochemical and metabolic changes These changes increase overall metabolic consumption in the host, especially in the skeletal muscle, and decrease lean body mass. Zemlickis and colleagues [7] found that patients diagnosed with breast cancer during pregnancy exhibited more advanced tumours and a higher incidence of metastasis compared to non-pregnant controls. Pregnant patients with cancer can exhibit a more advanced evolution of the disease due to delays in diagnosis and because the hormonal and physiological changes that accompany pregnancy can result in a more aggressive disease response
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