Evaluation of the placental proteomic profile in rats with Walker 256 tumor and under a leucine-rich diet intervention

• Grant number: 22/02114-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): May 01, 2022
• Effective date (End): April 30, 2025
• Field of knowledge: Health Sciences - Nutrition - Malnutrition and Physiological Development
• Principal Investigator: Maria Cristina Cintra Gomes Marcondes
• Grantee: Igor Fernando dos Santos
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 17/02739-4 - Nutrition and cancer: study of molecular, proteomic and metabolomic aspects of experimental model of cachexia, AP.TEM

Abstract

The main objective of the physiological alterations of pregnancy is the healthy development of the fetus-pregnant dyad, and, among these alterations, the placenta stands out, which acts as a selective and communication barrier. However, even with the natural protection mechanisms, the organism is subject to suffering of pathologies that can potentially affect the course of pregnancy, and, among these pathologies, there is cancer. According to the literature, breast cancer is the leading cause of cancer-related death in pregnant patients. Also, with changes in lifestyle habits, such as the staging of pregnancy for older ages, this incidence has been increasing in recent years. One of the several consequences that the presence of cancer can potentially cause in the placental tissue is the alteration in the healthy functioning of protein synthesis and degradation. Literature has demonstrated the importance of studying proteins in relation to different pathologies, since with the application of proteomics technologies it is possible to map the protein patterns of biological systems and use this information to identify disturbances possibly caused by disease progression. However, in relation to carcinogenesis, there is a lack of data on comparative protein mapping between placentas from healthy, diseased and under nutritional intervention organisms. An adjuvant nutritional supplement in the treatment of cancer, with the potential to mitigate alterations in protein production, is leucine, an amino acid that acts by inducing the protein synthesis process. Thus, one of the hypotheses of this experiment is that this mechanism may mitigate proteomic changes in the placenta caused by the presence of a tumor. Thus, the aim of this study is to understand the placental proteomic changes caused by the development of cancer, in an experimental model, and also to compare with data obtained from the placentas in the control group (healthy), and also to evaluate the effects of the leucine-rich diet. For this purpose, the development plan of this research has pre-clinical experimentation, using placentas from Wistar rats and the application of the Walker 256 carcinosarcoma model. The animals will be divided into the following four experimental groups: (1) control pregnant rats - with a healthy body; (2) pregnant rats with cancer; (3) pregnant rats undergoing nutritional intervention with leucine and (4) pregnant rats with cancer and undergoing nutritional intervention with leucine. The Walker 256 tumor will be inoculated into the rats as soon as the pregnancy is identified. The euthanasia will occur on the twentieth day of pregnancy, considering that the usual course of gestation of these animals lasts 21 days, and, after that, the placentas will be collected, weighed, frozen and stored for the subsequent proteomic analysis. (AU)