Effects of maternal protein restriction associated with sugar consumption on metabolism, reproductive parameters and prostatic morphophysiology in the offspring of rats

The increase of metabolic syndromes in our society has been associated with maternal and offspring nutritional factors, such as the maternal low protein diet (MLP) and the increase of sugar-products consumption from infancy to adult life. Epidemiologic and experimental researches showed both conditions have negative effects on the male reproductive system. In addition to affecting adult life, also occurring alterations in the aging, such as the development of prostate carcinoma in situ. The aim was to evaluate if the MLP and postnatal sugar consumption impacted the reproductive organs (ventral prostate- VP, testis, and epididymis) on a postnatal day (PND) 90 and if they cause relevant alterations in the proteomic profile of VP that reflect in morphophysiological parameters on adult animals, impacting in possible prostatic pathologies during aging, on PND 540. Male Sprague Dawley rats born from dams fed a control diet (17% protein) or hypoprotein diet (6% protein) during gestation and lactation periods, on PND 21 were divided into 4 groups and all started to receive the control diet: Control (CTR): born from CTR dams who consumed normal water ad libitum; Control+sugar (CTR+SUG): consumed 10% sugar solution diluted in water from PND 21 to PND 90; GLLP: born from GLLP dams who consumed normal water ad libitum; GLLP+SUG: Born from GLLP dams, who consumed sugar solution from PND 21 to PND 90. After PND 90 all animals consumed normal water. The animals were euthanized on PND 90 and 540. On PND 90, the ventral prostates, testis, and epididymis were collected for morphophysiological, proteomic and sperm count analyses. The proteomic prolife of VP was analysed in both ages (PND 90 and 540), additionally it was done the oral glucose tolerant test (OGTT) and the serum metabolic profile. The total proteins, triglycerides, glucose, and total cholesterol did not have any changes in both ages. The OGTT, the CTR+SUG group showed higher glycemia in 120 minutes and an increase of area under the curve (AUC) in relation to the CTR group, which characterize glucose intolerance. Both age the body weight and anogenital distance (AGD) were reduced in GLLP s groups. The VP weight did not have any change on PND 90, while in the aging this parameter was reduced in GLLP and GLLP+SUG groups. In the principal component analysis, on PND 90 the experimental groups had a similar distribution among the groups, in the aging the samples of each experimental group had a distinct distribution, especially the GLLP+SUG group. Proteins set enrichment analysis in the groups that consumed sugar showed terms related to the autophagy and glucose metabolism since PND 90, persisting until the aging, while the MLP diet altered pathways related to cell cycle, cellular proliferation, and estrogen pathways. The enriched terms in each age by differentially expressed proteins (DEP) are reflected in the morphophysiological alterations visualized on PND 90 and 540. Since both ages showed variations in the compartment frequency in the epithelium, lumen, and stroma in CTR+SUG, GLLP, and GLLP+SUG groups and PND 540, the development of some lesions such as atrophy, dysplasia, and carcinoma in situ. The reproductive parameters analyzed showed morphometric alterations in the epididymis, a decrease in sperm count in testis and epididymis, and transit spermatic time. Therefore, these results have shown that the MLP diet associated with postnatal sugar consumption can enhance the effects in reproductive functions and, especially, in the VP can contribute to the development of prostatic lesions in aging animals. (AU)