Differential ontogenetic exposure to obesogenic environment induces hyperproliferative status and nuclear receptors imbalance in the rat prostate at adulthood

Autor(es)

Pytlowanciv, Eloisa Zanin ^[1] ; Pinto-Fochi, Maria Etelvina ^[2] ; Reame, Vanessa ^[1] ; Gobbo, Marina Guimaraes ^[1] ; Ribeiro, Daniele Lisboa ^[3] ; Taboga, Sebastiao Roberto ^[2] ; Goes, Rejane Maira ^[2]

Afiliação do(s) autor(es)

^[1] Campinas State Univ UNICAMP, Inst Biol, Dept Struct & Funct Biol, Campinas, SP - Brazil

^[2] Univ Estadual Paulista UNESP, Inst Biosci Letters & Exact Sci, Dept Biol, Sao Jose Do Rio Preto, SP - Brazil

^[3] Univ Fed Uberlandia, Inst Biomed Sci, Histol Sect, Av Engenheiro Dinz 1178, CP 593, BR-38400 Uberlandia, MG - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PROSTATE; v. 76, n. 7, p. 662-678, MAY 15 2016.
• Citações Web of Science: 2

Resumo

BACKGROUNDExperimental data indicate that high-fat diet (HFD) may alter proliferative activity and prostate health. However, the consequences of HFD exposure during different periods of ontogenetic development on prostate histophysiology remain to be elucidated. Herein, we compare the influence of obesogenic environment (OE) due to maternal obesity and HFD at different periods of life on proliferative activity and nuclear receptors frequency in the rat ventral prostate and a possible relationship with metabolic and hormonal alterations. METHODSMale Wistar rats (19 weeks old), treated with balanced chow (Control groupC; 3% high-fat, 3.5Kcal/g), were compared with those exposed to HFD (20% high-fat, 4.9kcal/g) during gestation (Gmaternal obesity), gestation and lactation (GL), from post-weaning to adulthood (WA), from lactation to adulthood (LA) and from gestation to adulthood (GA). After the experimental period, the ventral prostate lobes were removed and analyzed with different methods. RESULTSMetabolic data indicated that G and GL rats became insulin resistant and WA, LA, and GA became insulin resistant and obese. There was a strong inverse correlation between serum testosterone (approximate to 133% lower) and leptin levels (approximate to 467% higher) in WA, LA, and GA groups. Estrogen serum levels increased in GA, and insulin levels increased in all groups, especially in WA (64.8x). OE-groups exhibited prostatic hypertrophy, since prostate weight increased approximate to 40% in G, GL, LA, and GA and 31% in WA. As indicated by immunohistochemistry, all HFD-groups except G exhibited an increase in epithelial cell proliferation (PCNA-positive) and a decrease in frequency of AR- and ER-positive epithelial cells; there was also an increment of ER-positive stromal cells in comparison with control. Cells containing PPAR increased in both epithelium and stroma of all OE groups and those expressing LXR decreased, particularly in groups OE-exposed during gestation (G, GL and GA). CONCLUSIONSOE leads to prostate hypertrophy regardless of the period of development and, except when restricted to gestation, leads to a hyperproliferative status which was correlated to downregulation of AR and LXR and upregulation of ER and PPAR signaling. Prostate 76:662-678, 2016. (c) 2016 Wiley Periodicals, Inc. (AU)

• Processo FAPESP: 09/16071-9 - Efeitos da obesidade materna e supernutrição pós-natal sobre o aparelho genital masculino de ratos: avaliação morfofuncional das células de leydig
• Beneficiário: Maria Etelvina Pinto Fochi
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 11/01612-4 - Efeitos da obesidade materna e supernutrição pós-natal sobre o aparelho genital masculino de ratos: avaliação morfofuncional das células de Leydig
• Beneficiário: Rejane Maira Góes
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/03596-6 - Efeito comparativo da obesidade em diferentes fases do desenvolvimento sobre a histofisiologia da próstata ventral de ratos: possíveis relações com hormônios esteroides e a expressão da enzima 5 alfa-redutase
• Beneficiário: Eloísa Zanin Pytlowanciv
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 13/18011-9 - Repercussões da obesidade materna e/ou pós-natal sobre as células de sertoli e a expressão de fatores parácrinos intra-testiculares
• Beneficiário: Vanessa Reame
• Modalidade de apoio: Bolsas no Brasil - Mestrado