Programação fetal por restrição proteica: avaliação estrutural da próstata ventral de ratos wistar
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Data
2020-05-08
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Universidade Estadual Paulista (Unesp)
Resumo
A programação fetal (PF) é o resultado permanente do organismo na presença de estímulos ocorridos durante os períodos críticos de desenvolvimento. Vários fatores ambientais podem levar à PF. Entre eles, podemos citar a restrição alimentar materna ou a deficiência específica de nutrientes. De acordo com a janela de programação fetal masculinizante (MPW), os andrógenos agem para assegurar o desenvolvimento normal dos órgãos reprodutores do macho, assim, foram estudados os efeitos da restrição proteica materna durante a gestação e lactação sobre o desenvolvimento da próstata ventral de ratos Wistar. Para isto, dois grupos de ratas gestantes foram alimentadas com dietas isocalóricas, sendo um grupo normoproteico (NP) e o outro grupo hipoproteico (RP). Os grupos NP e RP tiveram livre acesso à dieta durante os períodos de gestação e lactação. Após o desmame, metade da prole de machos foi eutanasiada. A outra metade da prole de machos recebeu dieta padrão de animais de laboratório até os 120 dias de idade. A próstata ventral foi estudada por imuno-histoquímica para a avaliação da localização do antígeno de proliferação celular (PCNA), da proteína p63, dos receptores de andrógeno (AR), de estrógeno alfa (ER-α), de grelina (GHSR-1a), de leptina (Ob -R). Os pesos corpóreo, da próstata ventral, dos testículos e do tecido adiposo e os níveis de testosterona e estradiol foram obtidos. A PF determinou atraso no crescimento somático dos animais do grupo RP e diminuição do estradiol plasmático dos animais adultos do grupo RP. Aos 21 dias de idade, os animais do grupo RP apresentaram imunomarcação menos intensa para o ER-α, GHSR- 1a e Ob-R comparada aos animais do grupo NP. Aos 120 dias, os animais do grupo NP apresentaram imunomarcação menos intensa para o ER-α e AR, e imunomarcação mais intensa para o GHSR- 1a e Ob-R comparada aos animais do grupo NP. A análise dos índices de proliferação celular indicou não haver diferenças entre os grupos estudados de acordo com as duas idades. O estudo da frequência de células p63+ no lobo ventral da próstata dos animais dos grupos NP e RP mostrou que a PF interferiu somente na população de células basais aos 21 dias de idade. O grupo RP apresentou mais células basais p63+. Neste estudo observou-se que a exposição do feto ao baixo teor de proteínas durante o desenvolvimento pré-natal e perinatal programou o atraso no crescimento somático da prole dos 21 aos 120 dias e alterou o fenótipo epitelial das células do lobo ventral da próstata que expressam os receptores AR, ER-α, Ob-R e GHSR-1a e p63.
Fetal programming (FP) is the permanent result of the organism in the presence of stimuli during the periods of development. Several environmental factors can lead to FP. Among them, we can mention the maternal food restriction or deficiency of specific nutrients. According to the masculinization programming window (MPW) in which androgens act to ensure normal development of the male reproductive organs, we studied the effects of maternal protein restriction during pregnancy and lactation period on the development of the Wistar rat ventral prostate. Dams of the group (NP) were fed diet containing 17% protein; Dams of the group (RP) were fed diet containing 8% protein. The NP and RP groups had free access to diet during pregnancy and lactation period. After weaning, half of the male pups was killed. The other half of male pups received a standard laboratory diet until 120 days old. The ventral prostate was studied immunohistochemically to evaluate the expression of cell proliferation antigen (PCNA), p63 protein, androgen (AR), alpha estrogen (ER-α), ghrelin (GHSR-1a), leptin (Ob -R) receptors. The body, ventral prostate, testes and adipose tissue weights, testosterone and estradiol levels were determined. FP determined a delay somatic growth of the RP group and decrease of the plasmatic estradiol of the adult animals of the RP group. At 21 days of age, the RP group presented less intense immunostaining for ER-α, GHSR-1a, and Ob-R when compared to the NP group. At 120 days, the RP group showed less intense immunostaining for ER-α and AR, and more intense immunostaining for GHSR-1a and Ob-R when compared to the NP group. Analysis of cell proliferation rates does not indicate differences between the groups studied. The study of the frequency of p63+ cells in the ventral prostate showed that a FP interfered only in the population of basal cells at 21 days of age. The RP group presented more p63+ cells. This study showed that protein restriction during pregnancy and lactation delays the somatic growth from 21 to 120 days the postnatal development and alters the plasmatic estradiol and the epithelial phenotype of the rat ventral prostate epithelium, which express the AR, ER-α, Ob-R and GHSR-1a and p63.
Fetal programming (FP) is the permanent result of the organism in the presence of stimuli during the periods of development. Several environmental factors can lead to FP. Among them, we can mention the maternal food restriction or deficiency of specific nutrients. According to the masculinization programming window (MPW) in which androgens act to ensure normal development of the male reproductive organs, we studied the effects of maternal protein restriction during pregnancy and lactation period on the development of the Wistar rat ventral prostate. Dams of the group (NP) were fed diet containing 17% protein; Dams of the group (RP) were fed diet containing 8% protein. The NP and RP groups had free access to diet during pregnancy and lactation period. After weaning, half of the male pups was killed. The other half of male pups received a standard laboratory diet until 120 days old. The ventral prostate was studied immunohistochemically to evaluate the expression of cell proliferation antigen (PCNA), p63 protein, androgen (AR), alpha estrogen (ER-α), ghrelin (GHSR-1a), leptin (Ob -R) receptors. The body, ventral prostate, testes and adipose tissue weights, testosterone and estradiol levels were determined. FP determined a delay somatic growth of the RP group and decrease of the plasmatic estradiol of the adult animals of the RP group. At 21 days of age, the RP group presented less intense immunostaining for ER-α, GHSR-1a, and Ob-R when compared to the NP group. At 120 days, the RP group showed less intense immunostaining for ER-α and AR, and more intense immunostaining for GHSR-1a and Ob-R when compared to the NP group. Analysis of cell proliferation rates does not indicate differences between the groups studied. The study of the frequency of p63+ cells in the ventral prostate showed that a FP interfered only in the population of basal cells at 21 days of age. The RP group presented more p63+ cells. This study showed that protein restriction during pregnancy and lactation delays the somatic growth from 21 to 120 days the postnatal development and alters the plasmatic estradiol and the epithelial phenotype of the rat ventral prostate epithelium, which express the AR, ER-α, Ob-R and GHSR-1a and p63.
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Palavras-chave
Programação fetal, Receptor de andrógeno (AR), Receptor de leptina (Ob-R), Receptor de grelina (GHS-R 1a), Receptor de estrógeno, Próstata, Proliferação celular (PCNA), Fetal programming, Androgen receptor (AR), Prostate