Efeitos da restrição proteica materna associados ao consumo do açúcar sobre o metabolismo, parâmetros reprodutivos e morfofisiologia prostática na prole de ratos
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2021-03-25
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Universidade Estadual Paulista (Unesp)
Resumo
O aumento da incidência de síndromes metabólicas na população tem sido associado à fatores nutricionais maternos e da prole, como a restrição proteica materna (RPM) e o alto consumo de produtos com açúcares de adição da infância até a vida adulta. Estudos epidemiológicos e experimentais demonstram que ambos os tipos de fatores têm efeitos negativos sobre o sistema genital masculino. Além de efeitos negativos durante a fase adulta, também ocorrem alterações no envelhecimento, como a ocorrência de carcinoma in situ. Portanto, torna-se relevante investigar se a RPM modula parâmetros funcionais nos órgãos reprodutivos (próstata, testículo e epidídimo) da prole após ao consumo de açúcar pós-natal na idade adulta e no envelhecimento. O objetivo deste trabalho foi avaliar se a RPM e consumo pós-natal do açúcar afetam os órgãos reprodutivos (próstata ventral, testículo e epidídimo) e se o consumo de açúcar pós-natal afeta a morfofisiologia prostática nos animais adultos repercutindo em possíveis patologias no envelhecimento. Foram utilizados ratos Sprague Dawley machos nascidos de mães que receberam ração normoproteica (Controle- CTR, 17% proteína) ou hipoproteica (Restrição Proteica Gestacional e Lactacional- RPGL, 6% proteína) durante a gestação e a lactação, no dia pós-natal 21 (DPN- desmame) os machos foram divididos em 4 grupos e todos passaram a receber a ração normoproteica: Controle (CTR): nascidos de mães CTR que consumiram água normal ad libitum; Controle+açúcar (CTR+AÇÚ): consumiram solução de açúcar a 10% diluída em água do DPN 21 ao DPN 90; RPGL: nascidos de mães RPGL que consumiram água normal ad libitum; RPGL+AÇÚ: Nascidos de mães RPGL, que consumiram solução de açúcar do DPN 21 ao DPN 90. Após o DPN 90 todos os animais consumiram água normal. Os animais foram eutanasiados no DPN 90, onde foram coletadas as próstatas ventrais, testículos e epidídimos para análises morfofisiólogas e de contagens espermáticas; além disso para a próstata ventral de ambas as idades (DPN 90 e 540) foi analisado o perfil proteômico. Adicionalmente, foram realizados os testes de tolerância a glicose oral (TTGO) e análise do perfil metabólico e sérico dos animais no DPN 90 e 540. Nos testículos e nos epidídimos foram feitas as análises de contagem espermática e morfofisiológicas no DPN 90. As proteínas totais, triglicerídeos, glicose e colesterol total não mudaram em ambas as idades. No TTGO, o grupo CTR+AÇÚ apresentou glicemia maior no tempo de 120 minutos e na área sob a curva (ASC), um aumento significativo em relação ao grupo CTR, o que caracteriza intolerância à glicose. Para os parâmetros de peso corpóreo e distância ano-genital em ambas as idades foram reduzidas nos grupos RPGL, sendo que a PV não apresentou diferença no peso. Nas análises de componente principal do perfil proteômico, no DPN 90 os grupos não tiveram distribuição distinta, já no DPN 540 tiveram distribuição mais distinta entre os grupos, em especial para o grupo RPGL+AÇÚ. Os grupos que consumiram o açúcar enriqueceram vias relacionadas à autofagia, metabolismo de glicose desde o DPN 90, persistindo até o envelhecimento, enquanto a RPM alterou vias relacionadas à proliferação celular, ciclo celular e vias de estrógenos. Os termos enriquecidos em cada idade pelas proteínas diferencialmente expressas podem ter refletido nas alterações morfofisiológicas visualizadas nos grupos tratados (CTR+AÇÚ, RPGL e RPGL+AÇÚ) nos DPNs 90 e 540. Além disso, no DPN 540 observou-se diferentes lesões como atrofia inflamatória, atrofia epitelial, displasia, além do carcinoma in situ nos animais dos grupos CTR+AÇÚ e RPGL. Para as análises dos parâmetros reprodutivos os animais dos grupos RPGL e RPGL+AÇÚ tiveram uma diminuição da contagem espermática além da diminuição do tempo de trânsito no epidídimo. Portanto, estas análises nos mostram que a RPM associada ao consumo de açúcar pós-natal pode potencializar os efeitos na função reprodutiva e que em especial na próstata ventral estes podem contribuir para o desenvolvimento de lesões prostáticas.
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.
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.
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Palavras-chave
Restrição proteica materna, Consumo de açúcar pós-natal, Próstata, Proteômica