Effects of perinatal protein restriction associated to sugar consumption on metabolism, reproductive parameters and prostate morphophysiology in rat offspring

Abstract

Perinatal protein restriction (PPR) has been associated with an increase in the incidence of cardiovascular and renal diseases, besides affecting the reproductive parameters and the development of some types of cancer. In addition, exposure of these individuals to a second insult in postnatal life may amplify the damage caused by PRR, increasing the incidence of these diseases with aging. Our group demonstrated that the PRR affects development and increases the incidence of prostatic lesions in the offspring of old rats. However, the molecular mechanisms that cause these changes are still poorly understood. Thus, this project has two distinct objectives: 1) to evaluate whether adult rats (90 days) submitted to PRR (gestation and lactation) are more susceptible to metabolic and reproductive alterations by the postnatal exposure to refined sugar consumption (most consumed form of sugar) when compared to rats born of normal gestation; 2) to investigate whether the maternal protein restriction followed by sugar consumption increases the incidence of metabolic changes and prostatic lesions in old rats (540 days). Sprague-Dawley rats will be divided in four experimental groups: 1- Control (CTR): rats born from mothers that will consume normal diet (17% protein) and water ad libitum during gestation and lactation; 2- control + sugar (CTR + SUG): the same treatment of CTR but they will consume sugar solution (10% diluted in water) from the postnatal day (PND) 21 until the end of the experiment; 3- perinatal Protein Restriction (PPR): rats born from mothers that will consume a hypoprotein diet (6% protein) during gestation and lactation and that posteriorly will consume normal diet and water ad libitum until the end of the experiment; 4 - PPR + SGU group: rats born from mothers fed with hypoprotein diet during gestation and lactation and that will consume normal ration and sugar solution (10% diluted in water) ad libitum from postnatal day 21 until the end of experiment. At PNDs 90 and 540, the animals will be anesthetized, weighted and euthanized. The blood will be collected for hormonal, metabolic and oxidative stress analysis. At PND 90, the testis and epididymis will be collected for histopathological analysis and the sperm morphology, number and motility will be evaluated too. The ventral prostate will be collected at both ages to perform histopathological analysis, as well as proteome by mass spectrometry (LC-Ms / Ms). From this last technique will be listed targets to be validated by RT-qPCR, immunohistochemistry and western blotting. Thus, it is expected to obtain an overview of the effects of fetal programming by protein restriction followed by sugar consumption on reproductive parameters and altered molecular pathways in the prostate of reproductive age animals and the repercussions on the incidence of lesions with aging. (AU)