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Inflammation and cancer: evaluation of CCL2 and TGF-beta pathways in prostatic carcinogenesis in old rats submitted to maternal protein restriction and sugar consumption until adult life

Grant number: 19/10410-8
Support type:Scholarships in Brazil - Master
Effective date (Start): November 01, 2019
Effective date (End): March 31, 2021
Field of knowledge:Biological Sciences - Morphology - Histology
Principal Investigator:Luis Antonio Justulin Junior
Grantee:Matheus Naia Fioretto
Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Epidemiological and experimental studies have demonstrated a higher rate of obesity, diabetes and cardiovascular diseases in the adult population of individuals whose mothers had inadequate conditions during pregnancy, such as maternal protein restriction (MPR). Recently, experimental studies have demonstrated that the reproductive system and reproductive capacity are also affected by MPR in the offspring of rats, males and females. Linked to this, the increasing increase in world consumption of "added sugar" has been associated with the global epidemic of cases of metabolic diseases. Therefore, this project aims to investigate the role of inflammation pathways in rats submitted to maternal protein restriction (MPR), to aging, which together were exposed to postnatal sugar consumption. Data from our group have already demonstrated the effects of MPR fetal Programming on the development and progenitor maturation of offspring, therefore the impacts of sugar consumption associated with this insult on aging intra-prostatic and systemic inflammation in these animals will be evaluated. Male offspring of Sprague Dawley rats submitted or not to MPR will be used. The offspring were divided into four experimental groups: Control (CTR): Rats born to mothers who consumed normal ration (17% protein) and water ad libitum during gestation and lactation; Control + sugar (CTR + SU): The same treatment of CTR and that consumed sugar solution (10% diluted in water) from the postnatal day 21 (PND21-weaning) until the 90 PND; Protein restriction (MPR): Rats born to mothers who consumed hypoprotein ration (6% protein) during gestation and lactation and who subsequently consumed normal ration (17% protein) and water ad libitum until the 90 PND; MPR + SU group: Rats born to mothers fed with hypoprotein ration during pregnancy and lactation and consuming sugar solution (10% diluted in water) from PND 21 to PND 90 and, consequently, normal ration and water ad libitum. After this period, all the rats consumed water and normal ration ad libitum until the DPN 540, in which they were anesthetized, weighed and euthanized. The collected blood will be used for systemic analysis, and the ventral prostate for morphological, immunohistochemical and molecular analyzes, focusing on the inflammation pathways. These results will bring important contributions to the understanding of the effects of MPR associated with postnatal sugar consumption on the development of prostatic disorders, with an emphasis on inflammation. This project fits in the line of research of the responsible, on the aging and the role of inflammation in the development of prostatic lesions. (AU)